DIABETES MELLITUS EPIDEMIOLOGY Diabetes is presents in 5% of pregnant women, more than 90% of whom have gestational diabetes mellitus.

GDM is defined as glucose intolerance detected during pregnancy, and it is the most common medical complication of pregnancy. PATHOBIOLOGY Pregnancy is characterized by insulin resistance, which begins in the second trimester and increases to term. Decrease maternal responsiveness to insulin may have a role in providing carbohydrates to the fetus because maternal metabolism is shifted toward greater use of lipids. Both greater resistance to insulin and inadequate beta cell function contribute to the development of GDM. DIAGNOSIS GDM is asymptomatic when diagnosed. The screening strategy for GDM remains controversial. Among ethnic/racial groups with a higher prevalence of GDM, universal screening may be most appropriate. In other settings, screening is reserved for those with GDM risk factors, including women older than 25 years and those who are overweight or obese, have a first degree relative with diabetes, or have delivered a large infant. The screening usually occurs at 24 to 28 weeks gestation with a glucose measurement obtained 1 hour after the ingestion of 50 gram of oral glucose. A serum glucose level greater than 140 mg/dl or whole blood glucose level greater than 170 mg/dl is considered positive. This cutoff values is 90% sensitive and 80% specific, and a 100 gram 3 hours glucose tolerance test is used to confirm the presence of GDM. With the rising prevalence of type 2 diabetes, its prevalence is equal to that of type 1 diabetes in pregnant women with preexisting diabetes. Whites classification stratified diabetic womens pregnancy risks according to the duration of diabetes and the presence of retinopathy, nephropathy, or heart disease. This classification has been simplified to uncomplicated type 1 and type 2 diabetes and those with hypertension or any diabetes associated complication.

RISK ASSESMENT Risk factors for maternal morbidity and relative contraindications to pregnancy include established renal disease (creatinine greater than 2.0 mg/dl or proteinuria or more than 2 gram/day), uncontrolled hypertension, severe gastroparesis, and atherosclerotic vascular disease. If creatinine clearance is less than 80 mL/min or proteinuria is greater than 2 gram/day, up to 50% of women will experience permanent further renal impairment during pregnancy. Because diabetic retinopathy progresses in 10 to 50% of pregnant women, an ophthalmologist should examine patients before pregnancy and each trimester. TREATMENT Tight blood glucose control begins before conception because organogenesis occurs early in the first trimester and tighter blood sugar control may decrease the incidence of congenital malformations and miscarriages. Hemoglobin A should be normal for at least 2 months before conception. Both angiotensin converting enzyme inhibitors and receptor blockers should be discontinued because of their potential teratogenic effects. Measurement of urinary protein and creatinine, along with an ophthalmologic examination, is appropriate. When pregnancy is diagnosed during a period of overt hyperglycemia associated with existing or newly diagnosed diabetes, hospitalization for rapid metabolic correction may be appropriate. Therapeutic goals are fasting blood glucose values of less than 90 mg/dL and 1 hour postprandial values of less than 120 to 140 mg/dL. Women must be able to participate in intensified monitoring, including measuring their blood glucose several times per day (fasting, after meals, evening, and a middle of the night when morning values are elevated). GENERAL MEASURES Dietary therapy is the initial management of those with GDM. The recommended diet during gestation is 30 to 35 kcal/kg/day based on ideal body weight, with a composition of 40 to 50% carbohydrate, 20% protein, and 30 to 40% fat. Calories are divided into three meals and three snacks a day, with calories partitioned as 10% at

breakfast, 30% at lunch, 30% at dinner, and 10% during each snack. Reducing breakfast calories, when insulin resistance is greatest, decreasing the percentage of calories from carbohydrates, and avoid foods with a high glycemic index can lower maternal glucose levels. With GDM, low intensity aerobic exercise may reduce maternal glucose levels and is advised, as long as it is not contraindicated for medical or obstetric reasons. Mild calorie restriction to an intake of 25kcal/kg actual weight per day is appropriate for obese women with GDM. Exercise caloric restriction should be avoided. Ketonemia adversely affets the fetus, and care must be taken to prevent starvation ketosis. MEDICALTHERAPY Approximately 15% of women with GDM will have fasting glucose level higher than 105 mg/dl on two occasions and require additional therapy. When nutritional therapy is inadequate, human insulin is the standard treatment, and the usual initial dose is 0.7 U/kg, administrated as a combination of short and intermediate acting insulin give in two to four injections per day to reach the fasting and postprandial target levels. Older sulfonylureas, such as chlopropamide and tolbutamide, cross the placenta and were contraindicated during pregnancy. However, second generation oral hypoglycemic agents, such as glyburide, do not cross the placenta and have been used in pregnancy. In general, the control achieved may be comparable to that with insulin therapy. However, before groups such as the American Diabetes Association and American College of Obstetrician and Gynecologists recommend such therapy, more experience is needed to exclude rare but clinically important adverse effects. For women already taking insulin, their requirements usually decrease slightly during the first trimester and then increase until term. During the ninth month, insulin needs are approximately 50% greater than at preconception, and the increase is greater in patients with type 2 diabetes, for whom the additional insulin resistance of pregnancy may increase requirements up to 2 U/kg/day. Insulin requirements decrease after delivery, and a week postprandial, insulin needs are reduced by approximately 50%. To avoid hypoglycemia, intravenous glucose should be constantly infused, with hourly glucose monitoring. Women with GDM usually normalize their blood glucose immediately postpartum, and follow up fasting glucose

values should be obtained after approximately 2 months to reassess glucose status. Breast feeding generally improves glycemic control and should be encouraged. PROGNOSIS Most women with uncomplicated type 2 diabetes do well during pregnancy. However, maternal risks, sudden fetal death, and perinatal mortality are slightly increased. Despite careful management, congenital malformations complicate 6 to 10% of pregnancies in diabetic women. Two thirds of women with GDM will have a recurrence in subsequent pregnancies, and diabetes will develop in up to 50% over the next 15 years. Maintaining optimal weight and regular physical activity should be encouraged to reduce the risk.