1. Gestational Diabetes: A Big Problem Now and A Bigger Problem Later
Steven G. Gabbe, M.D.
Dean, School of Medicine
Professor, Obstetrics and Gynecology
Vanderbilt University Medical Center

2. Gestational Diabetes: A Big Problem Now and a Bigger Problem Later
Learning Objectives:
1. Identify the increased risk of gestational diabetes mellitus and type 2 diabetes mellitus in African American, Hispanic, Asian, and Native American women
2. Describe the short-term and long-term morbidities for these women and their infants
3. Discuss the need to detect gestational diabetes in pregnancy, and methods presently in use for screening and diagnosis

3. Gestational Diabetes: A Big Problem Now and a Bigger Problem Later
Learning Objectives:
Explain the use of dietary therapy, the indications for insulin and glyburide, and strategies for monitoring maternal glucose control
Describe strategies to prevent or delay the development of type 2 diabetes mellitus in women who have had gestational diabetes mellitus

4. Epidemiology 4-7% of pregnancies in the United States
complicated by diabetes mellitus:
GDM: 90%
Types 1 and 2: 10%

5. Maternal Metabolism in Late Pregnancy
Reduced insulin sensitivity
Insulin resistance due to:
Hormonal changes
Human placental lactogen (hPL), leptin, TNF α
Progesterone, prolactin, cortisol
Increased placental insulin clearance

6. Carbohydrate Metabolism in Pregnancy
Beta-cell function in normal pregnancy
Beta-cell hypertrophy and hyperplasia
Increased beta-cell responsiveness
Insulin action
Reduced hepatic insulin sensitivity
Increased hepatic glucose production

7. Carbohydrate Metabolism in Pregnancy
Postprandial hyperglycemia
Accelerated starvation

8. Effect of Maternal Diabetes Mellitus On the Fetus

9. Definition From the 4th International Workshop, 1997
Gestational diabetes is defined as carbohydrate
intolerance of variable severity with onset or first
recognition during pregnancy. The definition
applies regardless of whether insulin is used for
treatment or the condition persists after
pregnancy. It does not exclude the possibility
that unrecognized glucose intolerance may
have antedated the pregnancy.
Incidence: 7%

10. Consequences of Gestational Diabetes: Why Bother to Screen?
Maternal
Subsequent diabetes mellitus, >50% with type 2
diabetes mellitus 15 years postpartum; shortened
life expectancy

11. Incidence of Type 2 Diabetes Mellitus After Pregnancy Complicated by GDM
Cumulative incidence of diabetes in high-risk and control participants. Yellow squares indicate overweight control subjects; orange triangles, normal-weight control subjects; green squares, overweight high-risk subjects; blue triangles, normal-weight high-risk subjects.
J.B. O’Sullivan, Body Weight and Subsequent Diabetes Mellitus, JAMA 1982;248(8):949-52

13. Consequences of Gestational Diabetes: Why Bother to Screen?
Fetal and Neonatal
Maternal hyperglycemia leads to fetal hyperglycemia and hyperinsulinemia
Macrosomia and trauma including shoulder dystocia; Hypoglycemia, Hypocalcemia, Hyperbilirubinemia
Increased perinatal mortality associated with fasting hyperglycemia
Long term morbidity: obesity, carbohydrate intolerance

14. Follow-Up Studies of Infants of Gestational Diabetic Mothers (IGDM) at Age 12
Metzger B., et al. ADA Annual Meeting, 1995

15. Gestational Diabetes Mellitus Approaches to Screening and Diagnosis
Detection:
All pregnant women should be screened for glucose intolerance since selective screening based on clinical attributes or past obstetric history has been shown to be inadequate.

16. Gestational Diabetes Mellitus Approaches to Screening and Diagnosis
High Risk:
Clinical characteristics consistent with a high risk of GDM (marked obesity, PCOS, personal history of GDM, glycosuria, strong family history), test as soon as possible. If negative, retest at weeks gestation.

17. Gestational Diabetes Mellitus Approaches to Screening and Diagnosis
Average Risk:
Testing at weeks gestation

18. Gestational Diabetes Mellitus Approaches to Screening and Diagnosis
Low Risk:
Includes women with all of the following characteristics:
<25 years of age
Normal body weight
No first degree relative with diabetes mellitus
Not a member of an ethnic group at increased
risk for type 2 diabetes
No history of abnormal glucose metabolism
No history of poor obstetric outcome
No glucose testing required, BUT not practical

19. Relative Risk of GDM by Race Adjusted for Maternal Age and Prepregnant PIBW
*** *
* P< *** P<0.001
Dooley, SL. Et al., Int. J. Gynecol Obstet 1991;35:13-18.

20. Detection
Screening with a 50g glucose load or in high risk women, a diagnostic OGTT
50g oral glucose load, administered between the 24th and 28th week, without regard to time of day or time of last meal, to all pregnant women who have not been identified as having glucose intolerance before the 24th week
Venous plasma glucose measured one hour later. Value of mg/dL or above in venous plasma indicates the need for a full diagnostic glucose tolerance test

21. Gestational Diabetes Mellitus 100g OGTT Diagnostic Criteria
Two or more of the following venous plasma concentrations must be met or exceeded:
O-Sullivan
NDDG
Carpenter/
Coustan
Fasting
90 mg/dL
105 mg/dL
95 mg/dL
1-hour
165 mg/dL
190 mg/dL
180 mg/dL
2-hour
145 mg/dL
155 mg/dL
3-hour
125 mg/dL
140 mg/dL

22. Gestational Diabetes Mellitus Treatment
Visits every 1-2 weeks until 36 weeks; then weekly
Dietary management:
calorie, no-concentrated-sweets diet
Capillary blood glucose monitoring

23. Exercise and GDM
A program of moderate physical exercise is recommended
20 minutes, 3 times/week

24. Surveillance of Maternal Diabetes
Check fasting and 1-hour or 2-hour postprandial glucose levels daily to assess efficacy of diet with self monitoring of capillary blood glucose.
Check fasting urine ketones in patients on caloric restriction.
If fasting capillary value > 95mg/dL and/or 1-hour value > 140 mg/dL or 2-hour value > 120mg/dL, insulin or glyburide therapy is required.

25. Glyburide vs. Insulin
404 women with GDM randomized to insulin or glyburide (Micronase, DiaBeta)
Both therapies showed comparable improvement in glucose control
8% of glyburide patients required insulin
Hypoglycemia (<40 mg/dL) more frequent with insulin (20% vs. 2%, p=0.03)
No differences in maternal complications, Cesarean delivery rate, neonatal outcomes
Conclusion: In women with GDM, glyburide is a clinically effective alternative to insulin therapy
Langer O, et al. N Engl J Med 2000;343:1134-8

26. Effect of Treatment of GDM on Pregnancy Outcomes
Control
N = 510
Intervention
N = 490
Serious Complication
23 (4%)
7 (1%)*
NICU Adm.
321 (61%)
357 (71%)*
Induction of Labor
150 (29%)
189 (39%)**
Cesarean Delivery
164 (32%)
152 (31%)
*P = 0.01
**P = < 0.001
Crowther, C.A., et al. N Engl J Med 2005;352:

27. Effect of Treatment of GDM on Pregnancy Outcomes
Control
N = 510
Intervention
N = 490
Gestational Age
39.3 wks
39.0 wks
LGA
115 (22%)
68 (13%)**
Macrosomia (≥ 4kg)
110 (21%)
49 (10%)**
**P = < 0.001
Crowther, C.A., et al. N Engl J Med 2005;352:

28. Effect of Treatment of GDM on Pregnancy Outcomes
Conclusions:
Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman’s health-related quality of life.
Crowther, C.A., et al. N Engl J Med 2005;352:

29. Evaluation for Carbohydrate Intolerance Postpartum Care
At 6-12 weeks postpartum, all patients who had carbohydrate intolerance during pregnancy (GDM) should be evaluated and reclassified as follows:

30. Evaluation for Postpartum Carbohydrate Intolerance
Normal
Impaired
Diabetes Mellitus
Fasting <100mg/dL
mg/dL
≥ 126 mg/dL
and
2hr <140mg/dL
2 hr ≥ mg/dL
2hr ≥ 200mg/dL

31. Gestational Diabetes and the Incidence of Type 2 Diabetes – A systematic literature review
Women of different ethnic groups progress to
type 2 diabetes at similar rates after a diagnosis of
GDM, 5-10%/year.
2. Incidence of type 2 diabetes increases markedly in first 5 years after delivery; plateaus at 10 years.
3. Elevated fasting glucose during pregnancy most important risk factor for type 2 diabetes.
Kim C, et al. Diabetes Care 2002;25:
Reed S, et al. Clinical Journal of Women’s Health 2002;2:29-33
Kjos S, et al. Diabetes 1995;44:586-91

32. Factors Associated with Accelerated Onset of Type 2 Diabetes Mellitus
Another pregnancy, especially complicated by GDM
Weight Gain; non-pregnant BMI ≥ 30
Use of progestin-only oral contraceptives in lactating Latina women with prior GDM
Hypertension
Family History of Diabetes Mellitus

33. Prevalence of Type 2 Diabetes in Various US Ethnic Groups
Abate N., Chandalia M. The impact of ethnicity on type 2 diabetes. Journal of Diabetes and Its Complications 2003;17:39-58.

34. Strategies for Prevention/Delaying Onset of Type 2 Diabetes Mellitus
Weight Loss
Healthy Diet
Exercise
Drugs: Metformin
Troglitazone (TRIPOD Study)

35. Cumulative Incidence Rates
Cumulative incidence of diabetes (%)
Buchanan T.A., et al. Preservation of Pancreatic β-Cell Function…Women, Diabetes, 2002;51:

36. Gestational Diabetes Mellitus Key Points
1. Pregnancy has been characterized as a diabetogenic state
because of increased postprandial glucose levels in late
gestation.
2. GDM is an important health care problem affecting
approximately 200,000 women annually.
3. Perinatal mortality is not increased in most cases of
GDM, although increased morbidity, primarily
macrosomia, is found in the offspring of women with
GDM.

37. Gestational Diabetes Mellitus Key Points
4. Universal screening for GDM using measurements
of blood glucose should be performed at weeks
gestation except for women identified as low risk based on
clinical attributes.
5. To better guide therapy, we must define the level of
glycemic control which poses a risk for fetal and neonatal
complications such as macrosomia.
6. The key element in treating gestational diabetes
mellitus is dietary therapy. Moderate exercise may
also be valuable.

38. Gestational Diabetes Mellitus Key Points
7. Insulin or glyburide are utilized when significant fasting
or postprandial hyperglycemia occurs despite dietary
treatment.
8. A program of fetal surveillance is appropriate for patients
with GDM requiring insulin or glyburide, or those with
hypertension or a previous stillbirth.
9. Women with GDM are at high risk for developing type 2
diabetes. Regular medical evaluations are therefore
recommended.