Fetal outcomes: Comparison of oral agents with diet controlled and insulin controlled gestational diabetes

1. Fetal outcomes: Comparison of oral agents with diet controlled and insulin controlled gestational diabetes Amanda Hatton, MD

2. Investigators • Amanda Hatton, MD • Selman Welt, MD • Samuel Prien, PhD

3. Background • Gestational diabetes affects from 1-14% of pregnant mothers1 • Levels of diabetogenic placental steroids and peptide hormones (estrogen, progesterone, chorionic sommatomammotrophin) rise linearly throughout the second and third trimester resulting in progressively increasing tissue resistance to insulin2 • Maternal insulin resistance requires a significant increase in pancreatic insulin production to more than twice non-pregnant levels • Failure to adequately compensate for increased demand of insulin production leads to maternal hyperglycemia followed by fetal hyperglycemia

4. Fetal health implications • Fetal hyperglycemia leads to fetal hyperinsulinemia which has detrimental consequences to fetal growth and well-being2 • Promotes storage of excess nutrients leading to macrosomia • Drives catabolism of oversupply of fuel, using energy and depleting fetal oxygen stores • Episodic fetal hypoxia leads to increased adrenal catecholamines causing hypertension, cardiac remodeling, and hypertrophy • Hypoxia also causes stimulation of erythropoietin which in turn increases hematocrit level and causes poor circulation and postnatal hyperbilirubinemia • At birth fetal hyperinsulinemia in absence of maternal glucose supply leads to hypoglycemia

5. Treatment of GDM • Glycemic monitoring, dietary regulation and medical therapy are used to control diabetes and prevent postnatal sequelae • Insulin discovered in 1922, successful management of diabetic pregnancies became possible and the frequency of antepartum fetal death decreased by one half2 • Glycemic control must be instituted early and aggressively if excellent newborn outcome is to be achieved • Oral agents such as acarbose and glyburide are aimed at augmenting insulin supply, decreasing insulin resistance, and limiting postprandial hypoglycemia • These agents have been shown to be an effective and safe alternative, since they do not significantly cross the placenta in vitro3

6. Objectives • To compare fetal outcomes in mothers with gestational diabetes treated with: • Diet - ADA diet, weight dependent, 3 meals and 3 snacks • Oral agents • Acarbose - alpha-glucosidase inhibitor, reversibly inhibits enzymes in the small intestine, delaying cleavage of oligosaccharides and disaccharides to monosaccharides • Glyburide - sulfonylurea compound, stimulates insulin release from the pancreatic beta cells, reduces glucose output from the liver and also increases insulin sensitivity at peripheral target sites • Insulin – weight based split mix dose of NPH and Novolog, insulin pump therapy, or long acting insulin with supplementation • This study was submitted to the IRB and was found to be exempt from formal IRB review

7. Experimental Design • Retrospective chart review • Identify mothers seen at Texas Tech Health Science Center (Lubbock) with gestational diabetes who were treated and delivered between January, 2005 and January, 2008 • Includes pregestational diabetics and those diagnosed by random blood sugar >200mg/dL or at least two abnormal values on a 3 hour 100g glucose challenge • All patients were provided with diabetic education, including nutrition guidance at the onset of their prenatal care in the case of preexisting diabetes or soon after diagnosis

8. General Treatment Guidelines Diet Fasting or preprandial >100 mg/dL, 20%  Glyburide 5-10mg daily Postprandials >120 mg/dL, 20%  Acarbose 25-100mg TID with meals Still uncontrolled  Insulin *control = fasting/preprandials <90 mg/dL, 80%, postprandial <120 mg/dL, 80%

9. Materials and Methods • Review mother’s and infant’s charts to compare outcomes of different treatment modalities • Class of gestational diabetes • Treatment and changes in treatment • Level of control • Complications of pregnancy • Mode of delivery • Fetal weight • Delivery complications • Fetal complications (hypoglycemia, hyperbilirubinemia, respiratory distress) • Patients diagnosed ≥ 36 weeks gestation will be excluded

10. Statistical Analysis • Continuous data will be evaluated with an analysis of variance (ANOVA) • Discrete data will be evaluated with a Chi-Square or Mann-Whitney U test

11. Results • We expect to find similar fetal outcomes in diabetic mothers with blood glucose levels that are well controlled by diet, oral agents or insulin • Thus far we have noted that there are no noticeable differences in outcomes pending a greater number of chart reviews and statistical analysis

12. References • 1. American College of Obstetrics and Gynecologists—Practice Bulletin Number 30 Gestational Diabetes, Washington, September 2001. • 2. Moore TR, Creasy RK, Resnik R: Diabetes in Pregnancy. Maternal-Fetal Medicine 53, pp. 964-985. W.B. Saunders Company, 1999. • 3. Klieger C, Pollex E, Koren G. (2008) Treating the mother—protecting the unborn: The safety of hypoglycemic drugs of pregnancy. J Mat Fetal Neonatal Med 21(3), pp. 191-196.