GESTATIONAL DIABETES MELLITUS

ANNABELLE MARIE101303061

B27

INTRODUCTION• 3-10% of pregnancies: abnormal maternal glucose

regulation• 90% due to gestational diabetes mellitus• Definition: glucose intolerance of variable degree with

onset or first recognition during pregnancy• Rising prevalence of diabetes: women have some form

of diagnosed diabetes particularly type II DM among women of childbearing age--- resulted in increasing number of pregnant women with pre-existing diabetes

• Type II- 8% of cases of diabetes mellitus in pregnancy and pre-existing diabetes mellitus now affects 1% of all pregnancies.

Pathophysiology• GDM characterised by hyperinsulinaemia and insulin

resistance resulting in abnormal carbohydrate intolerance.

• In first trimester and early second trimester, increased insulin sensitivity occurs due to relatively higher levels of estrogen

• in late second and early third trimesters, increased insulin resistance and rreduced sensitivity due to a number of antagonistic hormones especially, placental lactogen, leptin, progesterone, prolactin, cortisol and adiponection

IMPLICATIONS OF DIABETES IN PREGNANCY

DOUBLE risk of serious injury at birthTRIPLE likelihood of Caesarean deliveryQUADRUPLE incidence of Neonatal Intensive Care Unit admission

Effects of Pregnancy on Diabetes• Difficult to stabilise blood glucose during pregnancy due

to altered carbohydrate metabolism and impaired insulin action

• Insulin requirement increases as pregnancy advances• Accelerated starvation----rapid activation of lipolysis with

short period of fasting• Ketoacidosis can be precipitated durring

– hyperemesis gravidarum– infection– fasting of labour– Iatrogenically induced by sympathomimetics and corticosteroids

used in preterm labour

• Accelerates vascular changes

EFFECTS OF DIABETES ON PREGNANCY

Hyperglycaemia in 1st trimester

Impaired organogenesis

Congenital abnormalities

Chronic maternal hyperglycemia

Fetal hyperinsulinaemia

Fetal hyperglycaemia

Increased fetal oxygen demand

Glycosylated Hb carries less

oxygen molecule and

O2 binds more avidly and

releases O2 less

Decreased Oxygen tension (hypoxaemia)

Increase in anaerobic metabolism

increased lactate and acidaemia

Abortion/ IUD

Increased erythropoiesis

Polcythaemia and hyperviscosity

RBC breakdown and neonatal

hyperbilirubinaemia

Maternal hyperglycaemia

Fetal hyperglycaemia

Fetal osmotic diuresis

Polyhydramnios

Polyhydramnios

Fetal macrosomia

Fetal hyperinsulinaemia

fetal hypoglycaemia

Increased IGF

Obstructed labourShoulder Dystocia

Erb's palsy/ Birth Asphyxia

Decreased cortisol production

Respiratory distress syndrome

decreased surfactant synthesis

in lung

Maternal Complications of GDMDuring Pregnancy

Abortion

Preterm labour (due to infection or polyhydramnios)

Pre-eclampsia

Polyhydramnios

Maternal distress due to oversized fetus and polydramnios

Microangiopathy

Nephropathy, retinopathy, neuropathy

Large vessel disease

Coronary artery disease

Thromboembolic disease

Infection

Hypo and hyperglycaemia

During labour

Prolonged labour

Shoulder dystocia

Perineal injuries

PPH

Operative interference

Increased risk of Caesarean delivery

Puerperium

Puerperal sepsis

Lactational failure

Fetal Complications

1st trimester• Congenital

abnormalities– Cardiac : ASD, VSD– NTD– Sacral agenesis/ CRS– PCKD– Renal agenesis– Duodenal atresia– Tracheoesophageal

fistula

2nd Trimester• Macrosomia

Delivery• Birth asphyxia• Shoulder dystocia

After delivery• RDS• Hypoglycaemia• Polycythaemia• neonatal jaundice

Fetal and Neonatal Complications of diabetes in pregnancy

• Shoulder dystocia leading to brachial plexus injury and clavicular fracture---majority resolve and heal

within a few months

GESTATIONAL DIABETES PRE-EXISTING DIABETES

No increased risk of congenital anomalies

increases risk of fetal macrosomia

Increases risk of having Caesarean section

Increased risk for metabolic syndrome and type II diabetes later in life (>50%

women with gestational diabetes develop type II DM)

Babies born to women with gestation diabetes are at inceased risk for obesity,

glucose intolerance and diabetes in adolescence

Higher risk of congenital malformations and miscarriagesRecurrent urinary tract infections

Vulvovaginal infections with poor controlAssociated with risk of (PPPPRIM)

Pre-eclampsia,Polyhydraminos,

PPROM, Preterm labour,

Risk of operative deliveriesIUGR

MacrosomiaKetoacidosis in type I, progression of

microvascular complicationsCaesarean section rates invariably

increased due to fetal macrosomia, poor blood sugar control, polyhydramnios or

associated with failure of induction

Risk Factors• Age >25years• BMI >25kg/m²• Increased weight gain

during pregnancy• Previous history of large

for gestational age infants• History of GDM during

previous pregnancies• previous stillbirth with

pancreatic islet hyperplasia on autopsy

• Ethnic group ( East Asian, Pacific Island ancestry)

• Elevated fasting or random blood glucose levels during pregnancy

• Family history of diabetes in first degree relatives

• History of metabolic X syndrome

• History of type I or type II Diabetes Mellitus

• Unexplained fetal loss

Signs

Elevated serum glucose: severely elevated blood glucose level on random glucose testing excludes the need for screening

GLycosuria is od uncertain significance during pregnancy

Ketonuria

Elevated glycosylated haemoglobin

Ultrasound features such as greater than normal abdominal circumference

DIAGNOSISSymptoms

AsymtomaticInsidious onsetPolyuria, polyuria, polyphagia

Vague symptoms of fatige and abdominal discomfort and weight loss

Women with established diabetes may have symptoms such as retinopathy or neuropathy

SCREENING AND DIAGNOSTIC INVESTIGATION

• NORMAL

• Random blood glucose level 11.1mmol/L• Fasting blood glucose level 7.0mmol/L

• ABNORMAL

• Random bood glucose level ≥ 11.1mmol/L• Fasting blood glucose level ≥ 7.0mmol/L

Glucose Challenge test• 24-28 weeks gestation• 50g glucose drink given to the patient and blood

is drawn after 1 hour to measure blood glucose levels

• of the test result is positive i.e blood glucose level ≥ 7.2mmol/L (some clinicians use cut off as 7.8mmol/L), then the patient has to undergo the 3 hour 100g oral glucose tolerance test

Normal

Serum or plasma glucose level 7.2mmol/LSome clinician use a cut off of 7.8mmol/L

AbnormalSerum or plasma glucose level ≥ 7.2mmol/L or ≥ 7.8mmol/L

• Advantages• 2 step approach

identifies approximately 80% of women with gestational diabetes using of 7.8mmol/L and approximately 90% women with cut off 7.2mmol/L

• Disadvantages• False positives

common• Sensitivity of Glucose

tolerance screening varies with patient ethnicity

Indications

• Glycosuria on one occasion before 20th week and• 2 or more occasions thereafter

• Glycosuria occuring at anytime during pregnancy with• a positive family history of diabetes or past history of

having a baby 4kg or more.• Following positive screening test

• If FBG is more than 126mg/dL and if confirmed on repeat testing, there is no need to do MGTT

75g Oral Glucose Tolerance test- Modified Oral Glucose Tolerance (MGTT)

• Patient consume at least 150g carbohydrate for 3 days prior to test

• Patient should rest, no smoking, no drugs, no signs and symptoms of infection

• Fasting for 12hours is recommended and maternal venous blood is drawn to measure the fasting blood glucose level

• A 75g glucose in 300ml drink is given to the patient and blood is drawn at intervals to measure glucose levels.

• Only a fasting and 120min sample are needed

WHO Croteria for 2 hours 75g glucose tolerance test

whole blood venous (mmol/L)

whole blood capillary (mmol/L)

Plasma venous (mmol/L)

Plasma capillary (mmol/L)

Fasting >6.1 >6.1 >7.0 >7.1

2hrs >6.7 >7.8 >7.8 >8.9

Category Normal IGT Diabetes Mellitus

Fasting <5.6 5.6-7.8 >7.8

2hrs <7.8 7.8-11.1 >11.1

Other Screening TestsGlycosylated haemoglobin• Blood sample• Reflection f patients glycaemic control over the previous

2-3 months• Ordinarily decreased during pregnancy• Risk of fetal malforrmation correlates with degree of

hyperglycaemia during the first 6-8 weeks of gestation if HbA1c is 1% or more above normal

• Normal: 4.7-6.3% in non pregnant women,

4.5-5.7% in pregnant women

4.4-5.6% in late pregnancy

Advantage: does not require fasting plasma glucose

PRINCIPLES OF MANAGEMENT

Antenatal care• All diabetic women are managed in a multidisciplinary

combined obstetric and diabetic clinic with specialist obstetrician, diabetologist, specialist midwife, paediatrician and dietician

• All women should recieve dietary instruction, with individual recommendations based on weight and height

• Patient should recieve nutrition counselling from a registered dietician

• Daily calories should be made up approximately 40% carbohydrate, 20% proteins and 40% fats.

• This should improve blood glucose levels

Antenatal Care

Multidisciplinary approach

Dietary instructionwith individual

instruction based on height and

weight

Nutrition counselling from

registered dietician

Daily calories should be made up approximately 40% carbohydrate, 20% proteins and 40%

fats.

A daily intake of 2000 to 2200 :

30 kcal/kg for women with an ideal

prepregnancy weightIn women who are

obese (BMI: >30kg/m²), calorie

reduction by approximately one

third (to approximately 25kcal/kg/d) may be acceptable, although

caloric restriction during pregnancy

must be viewed with caution.

Non caloric sweetener used in

moderation

Increased fibre intake for

constipation

Vitamins and supplements

Avoid alcohol

Moderate exercise

Role of Ultrasound• Preferably done in first trimester to confirm gestational

age by dates• Repeated at 18 to 20 weeks gestation to evaluate the

fetus for congenital anomalies• Particularly important in patients with pre-existing type 1

and 2 diabetes and elvated first trimester HbA1c (>6.5%)• Should be done at 30 to 32 weeks and 36-38 weeks of

gestation to evaluate fetal size, amniotic fluid index, and to hlp ascertain the mode of delivery

Tests of fetal wellbeing• Daily fetal movement counting: 32

weeks gestation and continue until delivery

• Amniotic fluid index and biophysical profile:– these tests are usually conducted twice

weekly and are institued at 32 to 34 weeks of gestation in women on insulin and can be done from 34-36 weeks of gestation in women whose diabetes is controlled by diet

– Some clinician mahe patients with diet controlled gestational diabetes as they would a patient with a normal pregnancy without any additional testing.

Blood glucose monitoring• Maternal metabolic surveillance should

be directed at maintaining glycaemic control and detecting hyperglycaemia

• Target for blood glucose levels are usually

• 5.6mmol/L for fasting blood glucose

• 7.2mmol/L for 1hr postprandial blood glucose or

• 6.7mmol/L for 2hr postprandial blood glucose to reduce macrosomia

• Ideally daily self monitoring of blood glucose four times daily is recommended to establish glycaemic control. However in practice it is done fortnightly

• In patients requiring insulin therapy, glucose levels should be checked at least 4 times a day

• a glucose level measured first thing in the morning can rule out fasting hyperglycaemia and additional 1 or 2 hour postprandial values can ensure adequate glycaemic control

• In patients with diet controlled gestational diabetes, testing 4 times daily may be done once a fortnight

• Urine ketones need to be checked periodically during pregnancy

SUMMARYDiagnosis

Consult about diet and lifestyle

Do blood sugar profile after 1-2 weeks

If range between 4-7 mmol/l consider diet therapy

If >7mmol/l or type 1 diabetes or U/S show fetal macrosomia, start insulin (actrapid 4-6U tds). Can admit patient for

education therapyAntenatal visit fortnightly till 32

weeks, weekly after 32 weeks

During check up, monitor BSP and detect any complications

of DM

Fetus: 11-14weeks correct dating

Morphological scanning in 2nd trimester between 18-

22weeks

Serial scan for big baby, IUD, polyhydramnios

(accelerated growth rate of abdominal circumference

indicate macrosomia

HbA1c should check for every trimester (especially 1st

trimester) Maintain below 7%

Check for urinary tract infection and vaginal candidiasis

MEDICATIONS AND OTHER THERAPIES

• Human insulin is treatment of choice when blood glucose is not adequately controlled by diet

• Insulin therapy is indicated when diet does not maintain blood glucose levels at 5.8mmol/L for fasting blood glucose, 8.6mmol/L for 1 hr or 7.2mmol/L for 2hour postprandial blood glucose (Obs today)

• Insulin therapy also recommended if blood glucose levels are not controlled adequately by diet alone after two week trial

• Regular insulin is the preferred short acting insulin for pregnant patients.

• NPH insulin is the preferred intermediate acting insulin for pregnant patients

• Therapy is based preferably by self monitoring of blood glucose levels

• A patient newly started on insulin will begin at doses of 50-75% of the calculated dose

• Insulin dose should be individualised and adjusted according to the patient's blood glucose levels

Give actrapid 4-6U TDS

Monitor for 2 weeks

If still elevated increase until 12 U tds

If still cannot control add intermittent acting insulin (monotard)

If total of >30U per day, it indicate moderate-severe poor control of DM.

Adverse effects• Hypoglycaemia• Lipoatrophy or lipohypertrophy• Flushing• Rash• Urticaria• Acute edema• Hepatomegaly in high doses

Sulfonylureas

Insulin secretagoguesGLipizide, glyburideIncrease insulin secretion, decrease hepatic glucose production with resultant reversal or hyperglycaemia and indirect improvement of insulin sensitivity

MeglitinidesBiguanidesDecrease insulin resistance

Alpha glucosidase inhibitors eg acarbose) decrease intestinal absorption of starch and glucose

ThiazolidinedionesEg rosiglitazone and pioglitazone

Oral Antidiabetic agents• Has not been recommende in the part because of

concerns of potential teratogenicity and transport of glucose across the placenta

• Glyburide: does not cross the placenta in significant amounts and recent trials have said it is safe to use

• American College of Obstetricians and Gynecologists and ADA recommend not to prescribe it until further studies support its safetly and efficacy

• Include: Sulfonyl ureas (insulin secretagogues)

Time and mode of delivery• All pregnant women advised during the antenatal care about

the potential risks of pregnancy progressing beyond term• Gestational diabetes

– GDM on diet with no complications can be delivered at 40 weeks– GDM on insulin should be delivered by induction of labour at 38-39

weeks

• Pre-existing diabetes– Diabetes itself not an indication for Caesarean Section– Pregnant women with diabetes who have a normally grown fetus

should be offered elective birth through induction of labour, or by elective caesarean if indicated, after 38 completed weeks

– Pregnant women with ultrasound features of macrosomic fetus (fetal weight more than 4.5kg) and poorly controlled blood sugar are delivered by elective caesarean section.

Diabetes and C-section• Preoperative considerations

• Patient should take their evening dose of NPH insulin the night before the procedure

• Do not take the morning dose of insulin• If necessary, intravenous insulin infusion can be aded to

maintain normoglycaemia

• Intraoperative consideration• Maintain normoglycaemia

• Postoperative considerations:• Reassess glycaemic control after delivery

• Postpartum Management

• Blood glucose levels usually decline rapidly after delivery• Blood glucose levels should be reassessed at 6 weeks after

delivery, if not before, an then at 3 year intervals if levels are normal.

• If impaired fasting glucose or impaired glucose tolerance are observed postpartum, the patient should be tested annually for diabetes.

• All women with gestational diabetes should be counselled regarding diet, weight loss (if needed), and exercise in order to decrease the longterm risk of type 2

• patient with pre-existing diabetes should be transitioned to appropriate treatment postpartum (eg oral agent or adjusted insulin dosage)

• Contraception

• After 6 weeks or more following delivery, can diagnose Diabetes Mellitus if symptoms of diabetes mellitus are present

Random blood glucose 11.1mmol/L

Fasting blood glucose 7.0mmol/L

2hour post prandial 75g glucose tolerance test

11.1mmol/L

Resources• Obstetrics Today- 2nd edition Prof Sachichitanantham

and Dr Kavitha Nagandla• DC Dutta• Medscape