Gestational Diabetes

Just the Facts

Diabetes is the most common metabolic disorder of pregnancy

• 3-5% of all pregnancies• Affects more than 150,000 pregnancies each year• More than 7,000 are of women with Type 1 diabetes• 0.2 %-0.3 % of all pregnancies are complicated by pre-existing diabetes• more than 2 % of women of childbearing age have unrecognized Type 2

diabetes

• Onset of first recognition during pregnancy• A1 - controlled by diet and exercise• A2 – controlled by insulin

• Up to 3-7 % will develop Type 1 within 1 year• Up to 40-60 % will develop overt diabetes at 7-10 years post partum

unless lean & fit – 25 % risk

• Gestational Diabetes affects 3-14 % of all pregnancies and is one of the most common complications of pregnancy

• Results in 200,000 cases annually

Just the Facts - continued

• Age < 25• Weight normal before pregnancy• Member of an ethnic group with a low prevalence of GDM• No known diabetes in first-degree relatives• No history of abnormal glucose tolerance• No history of poor obstetric outcome

Low Risk For GDM

• Previous history of GDM• Neonatal course complicated by hypoglycemia• Classic diabetes symptoms• Marked obesity (>120%IBW or > 27 BMI)• Glycosuria• Strong family history of diabetes

Glucose screening as soon as feasible, if negative, retest 24-28 wks of gestation*

High Risk For GDM

• Usually given between 24-28 weeks

• 50g glucose challenge test (GCT)

• If 1-hr > 135 mg/dL, but < 200, OGTT needed (>130-140 mg/dL will identify 80-90%)

• FPG > 126 or casual BG> 200-diagnostic of DM

First Step Screening For GDM

100-g oral GTT (mg/dL)

FPG > 95 1-hr > 180 2-hr > 155 3-hr > 140

***(2 or more for positive diagnosis)***

Second Step-Diagnosis of GDM

• Maternal blood glucose levels are sustained longer to CHO load in pregnant state than in non-pg state

• Rising levels of ‘contra-insulin’ hormones modify maternal utilization of glucose and amino acids

• Glucose homeostasis is maintained by an exaggerated rate and amount of maternal insulin release accompanied by decreased insulin sensitivity due to placental hormones

Diabetogenic

• Diabet- o – genic• Insulin resistance caused by placental hormones around 24 weeks

gestation - causing elevated maternal blood glucose levels - Estrogen: increases pituitary prolactin - Progesterone & Human Placental Lactogen (HPL) - Cortisol

All antagonize the effect of insulin on muscle & fat

Later Pregnancy

MATERNAL:• Early pregnancy loss• Hydramnio• Preterm Labor• Increased risk of PIH/ Preeclampsia • DKA• Operative Delivery• Infection/ prenatal and postnatal

Risks

FETAL- NEONATAL:

• Prematurity• Stillborn• Macrosomia• Birth Trauma• Poor tolerance of labor• Hypoglycemia• Hypocalcemia• Hyperbilirubinemia• RDS

Risks

• Dietary Interventions

• Physical Activity

• Psychological Interventions- Lifestyle changes

• Maternal and Fetal Assessments -BG control --tight control can induce SGA in low risk situations -Fetal Ultrasound for Abdominal Circumference

Treatment Guidelines

Therapy focuses on:• Maternal BG goals • Fetal Size • Debate over definitions of somatic fetopathy

- US dating issues - Macrosomia vs. LGA - 4,000 Gms vs 4,250 Gms vs 4,500 Gms - Disproportionate growth: HC/AC.

• Neonatal morbidity• Physiologic instability (you need to increase the insulin given, there is

no available glucose)

Treatment

• Are you willing to check your blood sugar after meals?

• Are you willing to eat in the morning?

• Are you willing to change your breakfast choices from cold cereal to whole grain toast & egg?

• Can you replace soda with water?

Goal Setting

After reviewing blood sugars and food log you notice that 2 hour post-prandial BG are out of goal range. You might discuss food choices, portions, glycemic index. Carbohydrate consistency or carbohydrate counting may be in order.

You might make recommendations on reducing meal size, changing content to help post prandial BG.

Intervention

• Target Cells: muscle, liver, adipose, other• Principle Functions:

-stimulates glucose uptake by muscle & adipose -inhibits glucose output by liver -inhibits hydrolysis of triglycerides in adipose -stimulates amino acid uptake & protein synthesis -inhibits protein degradation in muscle and other cells -regulates gene transcription in numerous cell types

Summary of Functions of Insulin

10-15% of GDM’s will require insulin --Glyburide?

GDM Dx in First Trimester

Elevated A1C

LGA fetus (> 90th percentile) --Increasing abdominal circumference

Starting Insulin in GDM

If meal plan fails-Table 7. Insulin Action- See Handout

When FBS > 95

When 1 hr PP BS > 135/ 2 hr > 120

If FBS > 95 on GTT

Starting Insulin for GDM - continued

Currently, oral hypoglycemic agents are not recommended by the ADA or ACOG. The older sulfonylureas chlorpropamide and tolbutamide could cross the placenta, stimulate the fetal pancreas, and cause fetal hyperinsulinemia. However, the transfer of glyburide, a second-generation sulfonylurea across the human placenta was insignificant in experimental models.

This finding led to a clinical trial of 404 women with GDM randomized to either glyburide or insulin therapy at 11-33 weeks of gestation. There were no significant differences in glycemic control or adverse fetal outcomes. In addition, glyburide was not detected in the cord serum of any infants in the glyburide group.

Oral Agents

Smaller studies have also supported the safety of glyburide use in pregnancy. In one of these trials, women with GDM who were treated with glyburide had fewer asymptomatic hypoglycemic episodes compared to women with GDM treated with insulin, although the clinical significance of these hypoglycemic episodes is unknown.

Thus, although glyburide appears to be safe in pregnancy based on the above studies, it is important to recognize that these studies in aggregate are small and not adequately powered to detect clinically important, relatively rare outcomes in pregnancy. Furthermore, glyburide is considered to be in Pregnancy Category C by the FDA, and therefore is not currently recommended by the ADA or ADOG until larger studies confirm its safety. Another potential concern with the use of glyburide in GDM is possible impairment of myocardial ischemic pre-conditioning.

Oral Agents- Continued

Currently, oral hypoglycemic agents are not recommended by the ADA or ACOG. The older sulfonylureas chlorpropamide and tolbutamide could cross the placenta, stimulate the fetal pancreas, and cause fetal hyperinsulinemia. However, the transfer of glyburide, a second-generation sulfonylurea across the human placenta was insignificant in experimental models.

This finding led to a clinical trial of 404 women with GDM randomized to either glyburide or insulin therapy at 11-33 weeks of gestation. There were no significant differences in glycemic control or adverse fetal outcomes. In addition, glyburide was not detected in the cord serum of any infants in the glyburide group.

Oral Agents-continued

• A diagnosis of GDMA alone is not an indication for delivery before 38 weeks.

• Controversy exists regarding scheduling delivery between 38-40 weeks.• Incorporate EFW in deciding route of delivery• Fetal lung maternity test prior to induction or Cesarean section.• Intervene when:

-poor metabolic control, vascular disease, previous stillborn, IUFD, worsening retinopathy or poor program participation

• In the absence of any perinatal complications, allowing for spontaneous labor is recommended

Timing of Delivery

Maternal glycemic status should be reclassified 6 weeks or more after pregnancy ends and every 3 years thereafter as either diabetes mellitus, impaired fasting glucose tolerance, or normolglycemia. Normal values for a 2-hour OGTT are fasting < 100 mg/dl. All patients with a history of GDM should be educated about MNT, exercise, maintenance of normal body weight, the need for family planning, and symptoms suggestive of hypoglycemia.

Postpartum Considerations

• Adequate Nutrient intake

• Appropriate Weight Gain

• Blood Glucose in target range

• Limited episodes of hypoglycemia

• Patient satisfaction

• Healthy Newborn

Outcome Goals

GDM is a common medical problem that results from an increased severity of insulin resistance as well as an impairment of the compensatory increase in insulin secretion. Pregnancy, in essence, serves as a metabolic stress test and uncovers underlying insulin resistance and B-cell dysfunction. GDM is associated with a variety of maternal and fetal complications, most notably macrosomia.

Controversy surrounds the ideal approach for detecting GDM, and the approaches recommended for screening and diagnosis are largely based on expert opinion. Controlling maternal glycemia with MNT, close monitoring of blood glucose levels, and treatment with insulin if blood glucose levels are not at goal has been shown to decrease fetal and maternal morbidities. In addition, certain types of exercise appear to have potential benefits in women without any contraindications.

Conclusion

Other treatment modalities, such as oral agents, need further study to validate their safety and efficacy. Additionally, more research on the use of antepartum fetal assessment to help guide treatment in women with GDM is needed.

Finally, postpartum management of women with GDM is critical because of their markedly increased risk of type 2 diabetes in the future.

Conclusion - Continued

1. ACOG Educational Bulletin “Maternal Serum Screening” Number 228, September 1996.

2. ACOG Practice Bulletin “Prenatal Diagnosis of Fetal Chromosomal Abnormalities” Number 27, May 2001.

3. ACOG Technical Bulletin “Antepartum Fetal Surveillance” Number 188, January 1994.

4. ACOG Practice Bulletin “Gestational Diabetes” Number 30, September 2001.

5. American Diabetes Association. Medical Management of Pregnancy Complicated by Diabetes, 2nd Edition (every aspect of pregnancy and diabetes) 134 pages.

6. Casey BM, Lucas MJ, McIntire DD, Leveno KJ: Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population. Obslet Gynecol 90:869-873, 1997.

7. Creasy, RK, Resnick, R. Maternal Fetal Medicine, WB Saunders Company, 1999 4th Edition.

8. Dang K, Hombo C, Reece AE: Factors associated with fetal macrosomia in offspring of gestational diabetic women. J Matern Fetal Med 9:114-117, 2000.

9. Hellmuth E, Damm P, Molsted-Pederson: Oral Hypolglycaemic agents in 118 diabetic pregnancies. DIabet Med 17:507-511, 2000.

References