Post on 30-Sep-2020
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Diabetes in Pregnancy:
Detection, Intervention, Prevention
Michael Shannon, MD
Chair, Providence Endocrinology/Diabetes CAT
Diabetes in Pregnancy: Outline
Prevalence, Pathophysiology and Complications of
diabetes in pregnancy
Risk factors and screening of diabetes in pregnancy
Treatment of diabetes in pregnancy: nutrition, insulin
therapy, and newer technologies
Prevention of postpartum diabetes & recurrence (if
time allows)
Diabetes in Pregnancy
Approximately 200,000 pregnancies each
year are complicated by diabetes (up to 9.2%
of all pregnancies, CDC 2014)
Includes:
Type 1 (DM1)
Type 2 (DM2)
Gestational Diabetes Mellitus: any degree of
glucose intolerance, with onset or first
recognition during pregnancy (87% of cases)
13% DM at conception
2
Diabetes in Pregnancy: Pathophysiology
The hypoglycemic potency of insulin is diminished
[in pregnancy] as insulin resistance supervenes (N
Freinkel “Banting Lecture” 1980)
Possible candidates that increase across gestation –
hCG, E/P, human placental lactogen
Growth hormone-like activity is seen in the placenta
but unclear if contributor; other associations are
seen with leptin, IGFBP-1, and triglycerides
HD McIntyre et al, Diabetes Care 2018
Diabetes in Pregnancy: Pathophysiology
Diabetes in Pregnancy: Complications
There are two distinct groups of complications
Congenital malformations
These are related to 1st trimester hyperglycemia
Seen in pre-pregnancy diabetics only; not seen in
GDM, diabetic fathers, or pre-diabetics
Complications related to fetal macrosomia
Mostly related to fat deposition after 24-28 weeks
This 2nd-3rd trimester hyperglycemia causes birth
injury and possibly increased adult BMI, DM risk
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Infant Malformations Occur
Before the Seventh Gestational Week Anomaly
Ratio of incidence
Gestational age after ovulation in weeks
Caudal regression 252 3
Situs inversus 84 4
Spina bifida, hydrocephalus 2 4
Anencephalus 3 4
Renal anomalies 5
Agenesis 6 5
Cystic kidney 4 5
Ureter duplex 23 5
Heart anomalies
4 Transposition great vessels 5
Ventricular septal defect 6
Atrial septal defect 6
Anal/rectal atresia 3 6
JL Mills et al. Diabetes 1979
Diabetes in Early Pregnancy Trial Prevalence of Major Fetal Complications
Mills JL et al. NEJM. 1988
0
1
2
3
4
5
6
7
8
9
10
No Diabetes Early-entry diabetes Late-entry diabetes
9.0%
4.9%
2.1%
Prevalence
rate (%)
No Diabetes
Diabetes <21 days postconception
Diabetes >21 days postconception
Diabetes in Early Pregnancy (DIEP) Pregnancy Loss by A1C Status
JL Mills et al, NEJM 1988
0
5
10
15
20
25
30
35
40
45
–3 –2 –1 0 1 2 3 4 5 6 7 8 9
A1C: Standard deviation from control mean
Diabetes
No diabetes
Pregnancy
loss %
4
Fetal Macrosomia
Fetal macrosomia is closely related to glucose
levels in the 2nd, and especially the 3rd, trimester
Fetal macrosomia associated with adverse effects:
Shoulder dystocia and brachial plexus injury
Hepatomegaly and cardiomegaly
Neonatal hypoglycemia, other organ failure, NICU stay
Increased rate of C-sections
Best theorized with the Pedersen hypothesis
Fetal hyperinsulinemia
Maternal Glucose and Macrosomia Modified Pedersen Hypothesis
Fetus
Fetal pancreas stimulated
Mother
Pla
cen
ta
Insulin
Maternal hyperglycemia
Extra Glucose Stored as Fat:
Macrosomia and Insulin Resistance
Fetal Macrosomia
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Fetal Macrosomia
Macrosomia and Child Obesity
The neonatal environment and macrosomia may also
give “imprinting” on future obesity risk
A study of multi-ethnic women from 1990s and
measured offspring weight assessed 5-7 yrs later
Increasing maternal blood sugars was associated
with greater macrosomia and later childhood obesity
Even without macrosomia, however, maternal high
blood sugars nearly doubled the risk of childhood
obesity at age 5-7
TA Hillier et al, Diabetes Care 2007
At age 17, children of mothers with DM in pregnancy are
more likely to be overweight (whether GDM or pre-preg)
Zvi Laron et al, ADA 2013
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Obesity and Macrosomia: Cycle of
Maternal and Infant Consequences
Fetal/Neonatal
Macrosomia
Childhood
Obesity
Adult Obesity
and Diabetes
Obesitogenic and Diabetogenic Environment
Pregnancy with
GDM or DM2
Can glycemic control in pregnancy break obesity cycle?
Macrosomia and Child Obesity
The neonatal environment and macrosomia may also
give “imprinting” on future obesity risk
A study of multi-ethnic women from 1990s and
measured offspring weight assessed 5-7 yrs later
Increasing maternal blood sugars was associated
with greater macrosomia and later childhood obesity
Even without macrosomia, however, maternal high
blood sugars nearly doubled the risk of childhood
obesity at age 5-7
Successfully treated sugars greatly reduced
childhood obesity
TA Hillier et al, Diabetes Care 2007
Diabetes in Pregnancy
Approximately 200,000 pregnancies each
year are complicated by diabetes in
pregnancy (about 7-8% of all pregnancies)
Includes:
Type 1 (DM1)
Type 2 (DM2)
Gestational Diabetes Mellitus: any degree of
glucose intolerance, with onset or first
recognition during pregnancy (87% of cases)
13% DM at conception
7
Diabetic Pregnancies in the Past
Infant
mortality (%)
Mean maternal blood glucose (mg/dL)
Adapted from Jovanovic L, Peterson CM. Diabetes Care. 1980
Joslin <1922
Joslin 1924–38
Essex 1951–55
Pedersen 1969
Karlsson 1972
Joslin 1956–75
Tyson 1976
Martin 1979
Essex 1973 Karlsson 1972
Tyson 1979
100
50
0
0 100 200 DKA
Jovanovic 1980
What’s a Woman with Diabetes to Do?
Do women plan their pregnancies?
85 women with preconception DM; most women (79%) knew
should optimize their glucose before conception but fewer than
half (41%) of their pregnancies were planned
More planned pregnancies with higher income, private
insurance, education, happily married, and seeing an
endocrinologist
Most unplanned pregnancies were not contraceptive failures,
but may have been consciously or subconsciously intended.
Women who felt that their doctors discouraged pregnancy were
more likely to have an unplanned pregnancy than were women
who had been reassured they could have a healthy baby.
EV Holing et al, Diabetes Care 1998
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Preconception DM Care Possible Contraindications to Pregnancy
Coronary artery disease (heart attacks/stents)
Active, untreated severe diabetic retinopathy
Kidney insufficiency
Kidney function < 1/3 normal
Very large amounts of protein in urine
Very high blood pressure despite
treatment
Severe gastroparesis
American Diabetes Association, Diabetes Care
Who To Screen for GDM?
Increasing Rates of GDM
Source: CDC
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Increasing Rates of GDM
Source: DS Feig et al, Diabetes Care 2014
Increasing Rates of DM2 in Youth
Gestational Diabetes: Risk Factors
Overweight / obesity
Age
High risk ethnic group
Others: previous child > 9 pounds,
polycystic ovary syndrome, hypertension,
family history of gestational diabetes
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GDM: Age
Source: CDC
GDM: Body Mass and Ethnicity
Source: CDC
Who and How To Screen for GDM?
Screen almost all patients at 24-28 weeks
Screen high risk individuals at first prenatal visit and then retest at 24-28 weeks if negative on first screen
Patients for Early GDM
Testing Considerations
Maternal age >35 years
Previous infant >4kg
Previous GDM
Strong FH of Type II or
GDM
Obesity or PCOS
ADA Position Statement, Diabetes Care 2007
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ACOG: Screening and Diagnosis of GDM
Initial Screen: 50 g OGTT, test 1 hr glucose
If >140 or > 130 mg/dl requires further test
My option = consider > 180 mg/dl diagnostic
Diagnostic: fasting 100 g OGTT, at least 2+
Fasting glucose: 95 mg/dl
1 hour glucose: 180 mg/dl
2 hour glucose: 155 mg/dl
3 hour glucose: 140 mg/dl
Why not ADA/IADPSG Criteria?
One Step Approach recommended by IADPSG and one of two choices per ADA
Diagnostic: one or more elevated with 75 g
Fasting glucose: 92 mg/dl
1 hour glucose: 180 mg/dl
2 hour glucose: 155 mg/dl
Treatment of Diabetes in Pregnancy
Testing – well-timed, recorded, and lots of it
Treatment foundation is medical nutrition therapy
In patients who are not controlled by diet or pre-
existing diabetes, insulin is preferable (ADA)
ADA recommends insulin for optimal control
in Type 1 and Type 2 diabetics
ACOG has endorsed the use of oral agents
(metformin, glyburide, acarbose) and insulin
No oral DM agent is “approved” in pregnancy
All of this is better with diabetes educators!
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Self-Monitored Blood Glucose: SMBG Goals and Testing Frequency
Goals Timing
Fasting 60–95 mg/dL Test on waking
Premeal 60–95 mg/dL Test before each meal
1-hour postprandial 100–120 mg/dL Test 1 hour after each meal
Frequency
Preexisting
diabetes
7X/day =1 fasting + 2 premeal + 3 postprandial +
1 nighttime (2-4 AM) if hypoglycemia
The perfect is the enemy of the good (Voltaire)
Medical Nutrition Therapy
Treatment foundation is medical nutrition therapy
and intensive insulin therapy
Carbohydrate control at meals: 30 grams for
breakfast, 45-60 with lunch and dinner
15 gram snacks between meals
Post meal walking/exercise may reduce sugars
All of this requires diabetes educators!
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Oral Medications
Insulin is recommended as the standard treatment by
the ADA (ADA recommends discontinuing non-
insulins and starting insulin)
ACOG in Aug 2013 endorsed use of some orals
Glyburide is pill that stimulates insulin production in
pancreas; one good trial of this in 2000; can have lows’
Fifth International Workshop states caution in its use
Metformin has had some successful trials; many stay
on it (especially fertility docs); it does cross placenta
Limited trials on other diabetes drugs in pregnancy
Insulins “Approved” in Pregnancy
These are Category B by FDA in old system
Short acting insulins:
Regular insulin
Lispro (Humalog) insulin
Aspart (Novolog) insulin
Long acting insulins:
NPH insulin
Detemir (Levemir) insulin
Initiating Insulin Therapy in Pregnancy
If not controlled by diet, initiate stepwise insulin -> do
not let patients starve themselves away from insulin!
Give insulin for abnormal sugars
May only need at certain times (not all meals)
Need to analyze blood sugar readings to make
more specific interventions
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Initiating Insulin Therapy in Pregnancy
If not controlled by diet, initiate stepwise insulin -> do
not let patients starve themselves away from insulin!
Give insulin for abnormal sugars
High fasting sugars = bedtime long acting (NPH or
detemir)
Abnormal postprandial glucose with regular insulin
or rapid-acting insulin (lispro or aspart) imme-
diately before the meal with elevations
May only need at certain times (not all meals)
NPH
Insulin Algorithm Human Insulins (NPH/Regular)
4:00 16:00 20:00 24:00 12:00 8:00
NPH
Plasma
insulin
NPH
Breakfast
Regular
Lunch
Regular
Dinner
Regular
24:00
NPH
15
0600 0800 1800 1200 2400 0600
Time of day
20
40
60
80
100 B L D
Insulin Algorithm
With Category B Analog Insulin
Detemir (Levemir)
Lispro (Humalog) or Aspart (Novolog)
Normal pattern
U/mL
Carbohydrate Counting in Pregnancy
Carbohydrate counting
during pregnancy is essential
Detailed counting and carbo-
hydrate ratios with insulin
(i.e. 2 units per 15 grams)
Often different ratios as
different meals (more with
breakfast carbohydrates)
Harm reduction…
Optimizing Insulin in Pregnancy
Patients may do well with adjusting their own with
guidance: i.e. go up 2 units of bedtime insulin for
every two days your fasting sugars are > 90
Patients can use carbohydrate ratio dosing: i.e. take 3
units for every 15 grams (exchange) of carbohydrates
Patients can take VERY large doses of insulin… my
highest was 900 units per day
Where possible, insulin pens are a lot easier to teach
(for providers) and learn (for patients)
Patients will have (mostly) increasing insulin needs in
pregnancy -> the moving dartboard
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Newer Technology for
Diabetes in Pregnancy
Insulin Pumps
Insulin pumps can benefit many
pregnant diabetics; about 28% of
all DM1 patients have pumps, and
pregnancy may be a good time to
initiate pump usage
Patients should already be able to
manage frequent blood sugar
checks, count carbohydrates, and
give multiple daily insulin
injections (may need to show
insurance plans)
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Insulin Pump in Pregnancy - Data
2007 study of CSII showed no benefit
2016 Cochrane Review compared CSII vs MDI in
pregnancy – key findings
No evidence to support the use of one particular form
of insulin administration over another
Only a few trials appropriate for meta-analysis, a
small number of women included and questionable
generalisability of the trial population.
D Farrar et al, Cochrane Database of Systematic Reviews, 2016
Patient-Driven CGM
Patients can often utilize personal continuous
glucose monitoring for their sugars, especially
those with type 1 diabetes
Can pick up patterns in mealtime dosing and
basal rates -> also can separate out basal and
bolus problems with their interpretation
Sensors are not perfect and require calibration
and interpretation but newer technology is
(obviously, CDEs) an improvement
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Questions and Thanks to WADE
A hospital is no place to be sick.
Samuel Goldwyn (1882-1974)
What to expect at the hospital for delivery
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At the time of delivery…
Very little insulin is needed during active labor, and
some people need an IV with glucose to avoid ketones
RIGHT after pregnancy, insulin needs will drop
dramatically -> often reset almost all the way to pre-
pregnancy levels (plus some weight)
Go over postpartum insulin dosing with your doctor
After Delivery:
Patients with GDM can stop medications, and if
preexisting DM, usually can reduce or stop insulin
If GDM, need a 75 gram 2-hour glucose tolerance test
6-12 weeks after (this catches “unmasked” DM)
In 5-15 years, about half of women with GDM will
develop DM2 (about 7x normal population)
66% will have GDM in any subsequent pregnancy
(risks: can modify body weight, can’t change aging!)
Prevention: Future GDM
Weight loss: obese women who lost at least 10 pounds
between pregnancies reduced GDM risk by one third
Bariatric surgery in one study (of 700 women) reduced
the risk of gestational diabetes by three-quarters
Exercise may reduce gestational diabetes (mixed data)
Few studies on roles of specific dietary factors
How can I prevent or delay getting type 2 diabetes later in life?
You can do a lot to prevent or delay type 2 diabetes.
Reach and maintain a reasonable weight. Even if you stay above your ideal
weight, losing 5 to 7 percent of your body weight is enough to make a big
difference. For example, if you weigh 200 pounds, losing 10 to 14 pounds can
greatly reduce your chance of getting diabetes.
Be physically active for 30 minutes most days. Walk, swim, exercise, or go
dancing.
Follow a healthy eating plan. Eat more grains, fruits, and vegetables. Cut
down on fat and calories. A dietitian can help you design a meal plan.
Remind your health care team to check your blood glucose levels regularly.
Women who have had gestational diabetes should continue to be tested for
diabetes or pre-diabetes every 1 to 2 years. Diagnosing diabetes or pre-
diabetes early can help prevent complications such as heart disease later.
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Prevention: Future Type 2 Diabetes
Reach and maintain a reasonable weight. Even if you stay above
your ideal weight, losing 5 to 7 percent of your body weight is
enough to make a big difference.
Physically active for 30 minutes most days. Walk, swim,
exercise. (Accountability partner…)
Healthy eating plan. Eat more grains, fruits, and vegetables. Cut
down on fat and calories.
Check your blood glucose levels regularly. Women who have
had gestational diabetes be tested for diabetes or pre-diabetes
every 1 to 2 years; also recommend before next conception
How can I prevent or delay getting type 2 diabetes later in life?
You can do a lot to prevent or delay type 2 diabetes.
Reach and maintain a reasonable weight. Even if you stay above your ideal
weight, losing 5 to 7 percent of your body weight is enough to make a big
difference. For example, if you weigh 200 pounds, losing 10 to 14 pounds can
greatly reduce your chance of getting diabetes.
Be physically active for 30 minutes most days. Walk, swim, exercise, or go
dancing.
Follow a healthy eating plan. Eat more grains, fruits, and vegetables. Cut
down on fat and calories. A dietitian can help you design a meal plan.
Remind your health care team to check your blood glucose levels regularly.
Women who have had gestational diabetes should continue to be tested for
diabetes or pre-diabetes every 1 to 2 years. Diagnosing diabetes or pre-
diabetes early can help prevent complications such as heart disease later.