Gestational Diabetes

Michael Varner MD

Maternal-Fetal Medicine

University of Utah Health Sciences Center

Gestational DiabetesOutline

Trends in Diabetes

Physiology Pathophysiology

Definitions Diagnosis

Complications

Management

Common Types of Diabetes

bull Type 1 diabetesbull 5 to 10 of diagnosed cases of

diabetes

bull Type 2 diabetesbull 90 to 95 diagnosed cases of

diabetesNIDDK National Diabetes Statistics fact sheet HHS NIH 2005

Type 2 Diabetes

Family history Age Gestational diabetes Obesity

Risk Factors

Obesity Trends1990 2001

Diabetes Trends1990 2001

BRFSS 1990- 2001

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Gestational DiabetesOutline

Trends in Diabetes

Physiology Pathophysiology

Definitions Diagnosis

Complications

Management

Common Types of Diabetes

bull Type 1 diabetesbull 5 to 10 of diagnosed cases of

diabetes

bull Type 2 diabetesbull 90 to 95 diagnosed cases of

diabetesNIDDK National Diabetes Statistics fact sheet HHS NIH 2005

Type 2 Diabetes

Family history Age Gestational diabetes Obesity

Risk Factors

Obesity Trends1990 2001

Diabetes Trends1990 2001

BRFSS 1990- 2001

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Common Types of Diabetes

bull Type 1 diabetesbull 5 to 10 of diagnosed cases of

diabetes

bull Type 2 diabetesbull 90 to 95 diagnosed cases of

diabetesNIDDK National Diabetes Statistics fact sheet HHS NIH 2005

Type 2 Diabetes

Family history Age Gestational diabetes Obesity

Risk Factors

Obesity Trends1990 2001

Diabetes Trends1990 2001

BRFSS 1990- 2001

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Type 2 Diabetes

Family history Age Gestational diabetes Obesity

Risk Factors

Obesity Trends1990 2001

Diabetes Trends1990 2001

BRFSS 1990- 2001

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Obesity Trends1990 2001

Diabetes Trends1990 2001

BRFSS 1990- 2001

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Changing rates of GDM (1999-2005)

bull Southern California Kaiser-Permanente data base (175249 deliveries)

bull Pre-existing Diabetesndash 081 182 (p lt 0001)ndash Increases noted in all age-groups and all

racialethnic groups (but greatest increases in youngest women)

bull Gestational Diabetesndash 75 74 (NS)

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Diabetes Epidemic

bull The epidemic increase in diabetes in early 21st century Western societies is almost exclusively an increase in Type 2 diabetes

bull Type 2 diabetes is a disease of lifestyle (and therefore largely preventable)

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Gestational Diabetes

1048708 ldquoAny degree of glucose intolerance

with onset or first recognition during

pregnancyrdquo

1048708 7 of all pregnancies

1048708 More than 200000 cases annually

1048708 Range of prevalence 1-14 (higher in non-Caucasians)

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Teleology

Humans evolved as hunter-gathers

lsquoThrifty Genotype Phenotypersquo Competition between fetus

and mother for finite resources What would you do if you were

the fetus

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

lsquoEndocrinology of Pregnancyrsquo

bull The placenta produces larger quantities of more hormones than any other human organndash Human placental lactogenndash Estrogen progesterone

bull The majority of its products are released into the maternal circulation to induce changes on the fetusesrsquo behalf

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Glucose Metabolism in Pregnancy

bull Fetal growth is dependent upon maternal glucose

bull Carbohydrates from maternal diet

bull Stored glycogen converted to glucose

bull High levels of glucose transported by diffusion to the fetus

bull Fetal production of insulin

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Glucose Metabolism in Pregnancy

bull First Half of Pregnancy (Anabolic)ndash Pancreatic beta-cell hyperplasia causes

hyperinsulinemia ndash Increased uptake and storage of glucose

bull Second Half of Pregnancy (Catabolic)ndash Placental hormones block glucose receptors and

cause insulin resistancebull Increased lipolysisbull Increased gluconeogenesisbull Decreased glycogenesis

ndash Increased glucose and amino acids for the fetus

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Pedersen Hypothesis (1952)

bull Maternal hyperglycemia

bull Fetal hyperglycemia

bull Fetal hyperinsulinemia

bull Excess fetal fat

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

(Brief) History of GDM

bull Defined by Statistical Criteriandash 3-hour 100 gram oral glucose tolerance testndash Abnormal defined as 2 or more values at or above

two standard deviations above the meanbull Originally described to identify a group of women

at increased risk of type 2 diabetesbull Later identified as a group at increased risk of

pregnancy complications (Pedersen Hypothesis)bull The debate about the break point between

lsquonormalrsquo and lsquoabnormalrsquo continues to this day OSullivan J B Mahan C M Criteria for the oral glucose tolerance test in pregnancy Diabetes

196413278-85

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Causes of GDM

bull Inadequate insulin productionbull Increased insulin resistance

Or Both

bull Strong genetic predispositionbull Progressive increased risk until term (but most

clinically significant problems are evident by the early third trimester)

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

GDM Risk Factors

Family history Previous child gt 9 pounds Glycosuria Previous stillbirth ndash fetal

anomalies - polyhydramnios Maternal age (gt30) Non-Caucasian Obesity

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Screening for GDM (24 - 28 weeks)

bull ACOG Recommendations (2001)ndash Risk based approachndash States that ldquosince so few people have no

risk factors a universal screening program may be more practicalrdquo

bull United States (50 gram glucola ndash venous glucose at 1 hour thereafter)ndash Threshold = 130 ndash 140 mg

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS

OF GESTATIONAL DIABETES

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Whole Blood versus Plasma

Whole Blood (incl capillary)

Plasma

Fasting 90 105

1-hour 170 190

2-hour 145 165

3-hour 125 145

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

100 gm Oral GTT Criteria

NDDG Carpenter amp Coustan

Fasting 105 95

1-hour 190 180

2-hour 165 155

3-hour 145 140

All values in mg of venous blood

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

3-hr OGTT Testing

bull Should be done after an 8-14 hour fast

bull Should be done with patient sitting

bull A single abnormal value identifies a group at some increased risk but does not establish the diagnosis of GDM

bull Time of day does affect likelihood of diagnosis

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Screening for gestational diabetes (GD) the effect of screening time

Time Morning Afternoon(0930ndash1200) (1205ndash1710)

Number screened 176 470

Age in years (mean plusmn SD) 312 plusmn 47 317 plusmn 50

Weight (mean plusmn SD) 594 plusmn 105 kg 608 kg plusmn 129 kg

Family history of diabetes 27 24

Positive result 50 gm GTT 30 (170) 146 (311)

p lt 0001

Med J Aust 199816993-7

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

75 gm 2-Hour OGTT

Fasting 95 mg

1-hour 180 mg

2-hour 155 mg

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Adverse Pregnancy Outcomes

bull Maternal hyperglycemia ndash results in fetal hyperinsulinemia

bull Infantsndash Macrosomia

bull Shoulder dystociabull Operative delivery

ndash RDSndash Neonatal hypoglycemia jaundice

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Adverse Pregnancy Outcomes

bull Mothersndash Polyhydramniosndash Birth trauma operative deliveryndash 50-60 lifetime risk of developing type 2

diabetes

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Treatment Options

bull Diet

bull Exercise

bull Education

bull Medication

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Diet Therapy

bull Many women with GDM can control it with diet alone

bull May need medication (oral hypoglycemics or insulin) for control

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Exercise

bull Same guidelines as for women with pre-gestational diabetes

bull Walking and swimming are both good options

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Education - 1

bull Symptoms

bull Role of diet and exercise

bull Blood sugar goals

bull Technique and frequency for self-monitoring of blood sugars

bull How to complete blood sugar logs

bull Potential adverse outcomes of uncontrolled blood sugars

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Education - 2

bull Frequency of visits and antepartum testing

bull Potential for medication (including increasing dosages)

bull Effects of stress and infection on blood glucose levels

bull Risks for future diabetes

bull Risk reduction strategies

bull Need for lifelong follow up

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Blood Sugar Monitoring

bull Initially appropriate for those with elevated fasting glucosendash Demonstrate and return-demonstrate

equipmentndash Calibration and quality controlndash Use of lancet and proper techniques

bull Women with normal fasting glucose could be monitored at office visits

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Medications

bull Oral hypoglycemics

bull Insulin

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Oral Hypoglycemics

bull Adequate data suggest glyburide does not cross the placentandash The are no data for other sulfonylureas

bull A 10-25 primary failure rate is noted with glyburidendash More likely to occur in women with a BMI gt 41

kgm2 or higher initial fasting plasma glucose (gt 110 mgdL)

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Insulin

bull Initiate ifndash FBS gt 105 mgndash Postprandials gt 120 mg

bull Usually 2 injections dailybull Emphasize importance of glucose

monitoring and record keepingbull Injection site selectionbull Signs symptoms and treatment of

hypoglycemia (including family education)

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Fetal Surveillance Delivery

bull If on medications same as women with pregestational diabetes

bull Not necessary ifndash Diet-controlledndash No evidence of macrosomia or fetal

compromise

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Postpartum Glucose Testing after GDM

bull Retrospective cohort study of 344 women with GDM 2001-2004

bull Only 45 had postpartum glucose testingbull Of those 36 had persistent abnormal

glucose tolerancebull Recommendations

ndash Improve attendance at postpartum visitsndash Improve continuity between antepartum and

postpartum care

Obstetrics amp Gynecology 20061081456-1462

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

So where is the break point between normal and

abnormal carbohydrate metabolism in pregnancy

HAPOACHOIS (MFMU GDM)

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

HAPO(Hyperglycemia And Pregnancy Outcomes)

Followed gt 23000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes

Women with FBS gt 105 or 2-hr glucoses gt 200 were unblinded

Followed for BW gt 90th percentile primary cesarean neonatal hypoglycemia cord-blood C-peptide gt 90th percentile

NEJM 20083581991-2002

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

HAPO Conclusion

bull Strong continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels

bull The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

ACHOIS(Australian Carbohydrate

Intolerance Study)bull Randomized 1000 women with 2-hr 75 gram

glucose values 140-200 to treatment ndash no treatment (lsquonormal lt 155)

bull Treatment group Fewer serious perinatal complications and lower birth weights but more NICU admissions

bull Number needed to treat to prevent a lsquoserious complicationrsquo (death shoulder dystocia bone fracture nerve palsy) was 34

bull No change in cesarean rate

NEJM 20053522477-86

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

HAPO vs ACHOIS

bull If it takes 43 ACHOIS interventions (in women with GDM) to prevent one lsquoserious complicationrsquo how many women with borderline abnormal carbohydrate tolerance will we have to diagnose and treat in order to prevent one such problem

(I donrsquot know for sure but it will be a lot)

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

MFMU GDM Trial

bull lsquoMildrsquo GDM (Normal FBS elevation of 2 or 3 post-prandial values) randomized to unblinded treatment or blinded observation

bull Composite outcome of death birth trauma neonatal hypoglycemia or jaundice or elevated cord C-peptide

bull Recruitment ended October 2007 (enrollment = 1889) ndash last deliveries occurred in March 2008 (Utah was 2 in recruiting)

bull Results anticipated for January 2009 SMFM meeting

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary

Summarybull GDM requiring medical treatment identifies a

group of pregnant women at risk for multiple pregnancy complications and at increased long-term risk of type 2 diabetes

bull Lesser degrees of abnormal carbohydrate metabolism are also associated with an increased rate of pregnancy complications but the threshold for treatment non-treatment is not yet clear

bull Risks and complications of type 2 diabetes (and probably GDM) can be decreased by changes in lifestyle particularly diet and exercise

• Gestational Diabetes
• Gestational Diabetes Outline
• Common Types of Diabetes
• Type 2 Diabetes
• Obesity Trends
• Changing rates of GDM (1999-2005)
• Diabetes Epidemic
• Slide 8
• Teleology
• lsquoEndocrinology of Pregnancyrsquo
• Glucose Metabolism in Pregnancy
• Slide 12
• Pedersen Hypothesis (1952)
• Slide 14
• (Brief) History of GDM
• Causes of GDM
• GDM Risk Factors
• Screening for GDM (24 - 28 weeks)
• Slide 19
• Whole Blood versus Plasma
• 100 gm Oral GTT Criteria
• 3-hr OGTT Testing
• Screening for gestational diabetes (GD) the effect of screening time
• 75 gm 2-Hour OGTT
• Adverse Pregnancy Outcomes
• Slide 26
• Treatment Options
• Diet Therapy
• Exercise
• Education - 1
• Education - 2
• Blood Sugar Monitoring
• Medications
• Oral Hypoglycemics
• Insulin
• Fetal Surveillance Delivery
• Postpartum Glucose Testing after GDM
• So where is the break point between normal and abnormal carbohydrate metabolism in pregnancy
• HAPO (Hyperglycemia And Pregnancy Outcomes)
• Slide 40
• HAPO Conclusion
• ACHOIS (Australian Carbohydrate Intolerance Study)
• HAPO vs ACHOIS
• MFMU GDM Trial
• Summary