Gestational Diabetes

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Gestational Diabetes

• Michael Varner MD
• Maternal-Fetal Medicine
• University of Utah Health Sciences Center

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Gestational DiabetesOutline

• Trends in Diabetes
• Physiology / Pathophysiology
• Definitions / Diagnosis
• Complications
• Management

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Common Types of Diabetes

• Type 1 diabetes
• 5 to 10 of diagnosed cases of diabetes
• Type 2 diabetes
• 90 to 95 diagnosed cases of diabetes

NIDDK, National Diabetes Statistics fact sheet.
HHS, NIH, 2005.
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Type 2 Diabetes
Risk Factors

• Family history
• Age
• Gestational diabetes
• Obesity

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Obesity Trends
2001
1990
Diabetes Trends
1990
2001
BRFSS, 1990- 2001
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Changing rates of GDM (1999-2005)

• Southern California Kaiser-Permanente data base
  (175,249 deliveries)
• Pre-existing Diabetes
• 0.81 ?1.82 (p lt 0.001)
• Increases noted in all age-groups and all
  racial/ethnic groups (but greatest increases in
  youngest women)
• Gestational Diabetes
• 7.5 ?7.4 (N.S.)

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Diabetes Epidemic

• The epidemic increase in diabetes in early 21st
  century Western societies is almost exclusively
  an increase in Type 2 diabetes.
• Type 2 diabetes is a disease of lifestyle (and
  therefore largely preventable).

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Gestational Diabetes

• ?? Any degree of glucose intolerance
• with onset or first recognition during
• pregnancy
• ?? 7 of all pregnancies
• ?? More than 200,000 cases annually
• ?? Range of prevalence 1-14 (higher in
  non-Caucasians)

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Teleology

• Humans evolved as hunter-gathers
• Thrifty Genotype / Phenotype
• Competition between fetus and mother for finite
  resources
• What would you do if you were the fetus?

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Endocrinology of Pregnancy

• The placenta produces larger quantities of more
  hormones than any other human organ
• Human placental lactogen
• Estrogen / progesterone
• The majority of its products are released into
  the maternal circulation to induce changes on the
  fetuses behalf.

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Glucose Metabolism in Pregnancy

• Fetal growth is dependent upon maternal glucose
• Carbohydrates from maternal diet
• Stored glycogen converted to glucose
• High levels of glucose transported by diffusion
  to the fetus
• Fetal production of insulin

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Glucose Metabolism in Pregnancy

• First Half of Pregnancy (Anabolic)
• Pancreatic beta-cell hyperplasia causes
  hyperinsulinemia
• Increased uptake and storage of glucose
• Second Half of Pregnancy (Catabolic)
• Placental hormones block glucose receptors and
  cause insulin resistance
• Increased lipolysis
• Increased gluconeogenesis
• Decreased glycogenesis
• Increased glucose and amino acids for the fetus

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Pedersen Hypothesis (1952)

• Maternal hyperglycemia ?
• Fetal hyperglycemia ?
• Fetal hyperinsulinemia ?
• Excess fetal fat

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(Brief) History of GDM

• Defined by Statistical Criteria
• 3-hour 100 gram oral glucose tolerance test
• Abnormal defined as 2 or more values at, or
  above, two standard deviations above the mean
• Originally described to identify a group of women
  at increased risk of type 2 diabetes
• Later identified as a group at increased risk of
  pregnancy complications (Pedersen Hypothesis)
• The debate about the break point between normal
  and abnormal continues to this day.
• O'Sullivan J B, Mahan C M. Criteria for the
  oral glucose tolerance test in pregnancy.
  Diabetes 196413278-85.

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Causes of GDM

• Inadequate insulin production
• Increased insulin resistance
• Or Both!!
• Strong genetic predisposition
• Progressive increased risk until term (but most
  clinically significant problems are evident by
  the early third trimester)

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GDM Risk Factors

• Family history
• Previous child gt 9 pounds
• Glycosuria
• Previous stillbirth fetal anomalies -
  polyhydramnios
• Maternal age (gt30)
• Non-Caucasian
• Obesity

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Screening for GDM (24 - 28 weeks)

• ACOG Recommendations (2001)
• Risk based approach
• States that ...since so few people have no risk
  factors, a universal screening program may be
  more practical...
• United States (50 gram glucola venous glucose
  at 1 hour thereafter)
• Threshold 130 140 mg

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• A POSITIVE SCREEN DOES NOT ESTABLISH THE
  DIAGNOSIS OF GESTATIONAL DIABETES!!!

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Whole Blood versus Plasma
Whole Blood (incl. capillary) Plasma
Fasting 90 105
1-hour 170 190
2-hour 145 165
3-hour 125 145
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100 gm Oral GTT Criteria
NDDG Carpenter Coustan
Fasting 105 95
1-hour 190 180
2-hour 165 155
3-hour 145 140
All values in mg of venous blood
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3-hr OGTT Testing

• Should be done after an 8-14 hour fast
• Should be done with patient sitting
• A single abnormal value identifies a group at
  some increased risk, but does not establish the
  diagnosis of GDM
• Time of day does affect likelihood of diagnosis

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

• Time Morning Afternoon
• (09301200) (12051710)
• Number screened 176 470
• Age in years (mean SD) 31.2 4.7 31.7
  5.0
• Weight (mean SD) 59.4 10.5 kg 60.8 kg
  12.9 kg
• Family history of diabetes 27
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• Positive result, 50 gm GTT 30 (17.0) 146
  (31.1)
• p lt 0.001
• Med J Aust 199816993-7

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75 gm 2-Hour OGTT
Fasting 95 mg
1-hour 180 mg
2-hour 155 mg
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Adverse Pregnancy Outcomes

• Maternal hyperglycemia results in fetal
  hyperinsulinemia
• Infants
• Macrosomia
• Shoulder dystocia
• Operative delivery
• RDS
• Neonatal hypoglycemia / jaundice

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Adverse Pregnancy Outcomes

• Mothers
• Polyhydramnios
• Birth trauma / operative delivery
• 50-60 lifetime risk of developing type 2 diabetes

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Treatment Options

• Diet
• Exercise
• Education
• Medication

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Diet Therapy

• Many women with GDM can control it with diet
  alone
• May need medication (oral hypoglycemics or
  insulin) for control

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Exercise

• Same guidelines as for women with pre-gestational
  diabetes
• Walking and swimming are both good options.

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Education - 1

• Symptoms
• Role of diet and exercise
• Blood sugar goals
• Technique and frequency for self-monitoring of
  blood sugars
• How to complete blood sugar logs
• Potential adverse outcomes of uncontrolled blood
  sugars

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Education - 2

• Frequency of visits and antepartum testing
• Potential for medication (including increasing
  dosages)
• Effects of stress and infection on blood glucose
  levels
• Risks for future diabetes
• Risk reduction strategies
• Need for lifelong follow up

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Blood Sugar Monitoring

• Initially appropriate for those with elevated
  fasting glucose
• Demonstrate and return-demonstrate equipment
• Calibration and quality control
• Use of lancet and proper techniques
• Women with normal fasting glucose could be
  monitored at office visits

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Medications

• Oral hypoglycemics
• Insulin

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Oral Hypoglycemics

• Adequate data suggest glyburide does not cross
  the placenta
• The are no data for other sulfonylureas
• A 10-25 primary failure rate is noted with
  glyburide
• More likely to occur in women with a BMI gt 41
  kg/m2 or higher initial fasting plasma glucose (gt
  110 mg/dL)

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Insulin

• Initiate if
• FBS gt 105 mg
• Postprandials gt 120 mg
• Usually 2 injections daily
• Emphasize importance of glucose monitoring and
  record keeping.
• Injection site selection
• Signs, symptoms and treatment of hypoglycemia
  (including family education)

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Fetal Surveillance / Delivery

• If on medications, same as women with
  pregestational diabetes
• Not necessary if
• Diet-controlled
• No evidence of macrosomia or fetal compromise

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Postpartum Glucose Testing after GDM

• Retrospective cohort study of 344 women with GDM,
  2001-2004
• Only 45 had postpartum glucose testing
• Of those, 36 had persistent abnormal glucose
  tolerance.
• Recommendations
• Improve attendance at postpartum visits
• Improve continuity between antepartum and
  postpartum care
• Obstetrics Gynecology 20061081456-1462

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So where is the break point between normal and
abnormal carbohydrate metabolism in pregnancy?

• HAPO
• ACHOIS
• (MFMU GDM)

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HAPO(Hyperglycemia And Pregnancy Outcomes)

• Followed gt 23,000 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
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HAPO Conclusion

• Strong, continuous associations of maternal
  glucose levels below those diagnostic of GDM were
  seen with birthweight and increased cord-blood
  C-peptide levels.
• The current criteria for diagnosing and treating
  hyperglycemia during pregnancy needs to be
  re-evaluated.

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ACHOIS(Australian Carbohydrate Intolerance Study)

• Randomized 1000 women with 2-hr 75 gram glucose
  values 140-200 to treatment no treatment
  (normal lt 155).
• Treatment group Fewer serious perinatal
  complications and lower birth weights but more
  NICU admissions.
• Number needed to treat to prevent a serious
  complication (death, shoulder dystocia, bone
  fracture, nerve palsy) was 34.
• No change in cesarean rate.

NEJM 20053522477-86
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HAPO vs ACHOIS

• If it takes 43 ACHOIS interventions (in women
  with GDM) to prevent one serious complication,
  how many women with borderline abnormal
  carbohydrate tolerance will we have to diagnose
  and treat in order to prevent one such problem?
• (I dont know for sure, but it will be a lot)

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MFMU GDM Trial

• Mild GDM (Normal FBS, elevation of 2 or 3
  post-prandial values) randomized to unblinded
  treatment or blinded observation.
• Composite outcome of death, birth trauma,
  neonatal hypoglycemia or jaundice, or elevated
  cord C-peptide.
• Recruitment ended October 2007 (enrollment
  1889) last deliveries occurred in March 2008.
  (Utah was 2 in recruiting)
• Results anticipated for January 2009 SMFM
  meeting.

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Summary

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