2Just the FactsDiabetes is the most common metabolic disorder of pregnancy3-5% of all pregnanciesAffects more than 150,000 pregnancies each yearMore than 7,000 are of women with Type 1 diabetes0.2 %-0.3 % of all pregnancies are complicated by pre-existing diabetesmore than 2 % of women of childbearing age have unrecognized Type 2 diabetes
3Just the Facts - continued Onset of first recognition during pregnancyA1 - controlled by diet and exerciseA2 – controlled by insulinUp to 3-7 % will develop Type 1 within 1 yearUp to % will develop overt diabetes at 7-10 years post partum unless lean & fit – 25 % riskGestational Diabetes affects 3-14 % of all pregnancies and is one of the most common complications of pregnancyResults in 200,000 cases annually
4Low Risk For GDM Age < 25 Weight normal before pregnancy Member of an ethnic group with a low prevalence of GDMNo known diabetes in first-degree relativesNo history of abnormal glucose toleranceNo history of poor obstetric outcome
5High Risk For GDM Previous history of GDM Neonatal course complicated by hypoglycemiaClassic diabetes symptomsMarked obesity (>120%IBW or > 27 BMI)GlycosuriaStrong family history of diabetesGlucose screening as soon as feasible, if negative,retest wks of gestation*
6First Step Screening For GDM Usually given between weeks50g glucose challenge test (GCT)If 1-hr > 135 mg/dL, but < 200, OGTT needed (> mg/dL will identify 80-90%)FPG > 126 or casual BG> 200-diagnostic of DM
7Second Step-Diagnosis of GDM 100-g oral GTT (mg/dL)FPG > 951-hr > 1802-hr > 1553-hr > 140***(2 or more for positive diagnosis)***
8DiabetogenicMaternal blood glucose levels are sustained longer to CHO load in pregnant state than in non-pg stateRising levels of ‘contra-insulin’ hormones modify maternal utilization of glucose and amino acidsGlucose homeostasis is maintained by an exaggerated rate and amount of maternal insulin release accompanied by decreased insulin sensitivity due to placental hormones
9Later Pregnancy 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)- CortisolAll antagonize the effect of insulin on muscle & fat
10Risks MATERNAL: Early pregnancy loss Hydramnio Preterm Labor Increased risk of PIH/ PreeclampsiaDKAOperative DeliveryInfection/ prenatal and postnatal
12Treatment Guidelines Dietary Interventions Physical Activity Psychological Interventions- Lifestyle changesMaternal and Fetal Assessments-BG control--tight control can induce SGA in low risk situations-Fetal Ultrasound for Abdominal Circumference
13Treatment 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 morbidityPhysiologic instability (you need to increase the insulin given, there is no available glucose)
14Goal Setting 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?
15InterventionAfter 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.
16Summary of Functions of Insulin Target Cells: muscle, liver, adipose, otherPrinciple 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
17Starting Insulin in GDM 10-15% of GDM’s will require insulin--Glyburide?GDM Dx in First TrimesterElevated A1CLGA fetus (> 90th percentile)--Increasing abdominal circumference
18Starting Insulin for GDM - continued If meal plan fails-Table 7. Insulin Action- See HandoutWhen FBS > 95When 1 hr PP BS > 135/ 2 hr > 120If FBS > 95 on GTT
19Oral AgentsCurrently, 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 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.
20Oral Agents- Continued 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.
21Oral 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 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.
22Timing of DeliveryA diagnosis of GDMA alone is not an indication for delivery before 38 weeks.Controversy exists regarding scheduling delivery between weeks.Incorporate EFW in deciding route of deliveryFetal lung maternity test prior to induction or Cesarean section.Intervene when:-poor metabolic control, vascular disease, previous stillborn, IUFD,worsening retinopathy or poor program participationIn the absence of any perinatal complications, allowing for spontaneous labor is recommended
23Postpartum Considerations 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.
24Outcome Goals Adequate Nutrient intake Appropriate Weight Gain Blood Glucose in target rangeLimited episodes of hypoglycemiaPatient satisfactionHealthy Newborn
25ConclusionGDM 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.
26Conclusion - Continued 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.
27ReferencesACOG Educational Bulletin “Maternal Serum Screening” Number 228, September 1996.ACOG Practice Bulletin “Prenatal Diagnosis of Fetal Chromosomal Abnormalities” Number 27, May 2001.ACOG Technical Bulletin “Antepartum Fetal Surveillance” Number 188, January 1994.ACOG Practice Bulletin “Gestational Diabetes” Number 30, September 2001.American Diabetes Association. Medical Management of Pregnancy Complicated by Diabetes, 2nd Edition (every aspect of pregnancy and diabetes) 134 pages.Casey BM, Lucas MJ, McIntire DD, Leveno KJ: Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population. Obslet Gynecol 90: , 1997.Creasy, RK, Resnick, R. Maternal Fetal Medicine, WB Saunders Company, th Edition.Dang K, Hombo C, Reece AE: Factors associated with fetal macrosomia in offspring of gestational diabetic women. J Matern Fetal Med 9: , 2000.Hellmuth E, Damm P, Molsted-Pederson: Oral Hypolglycaemic agents in 118 diabetic pregnancies. DIabet Med 17: , 2000.