Criteria: Diabetes Mellitus in pregnancy can be broadly divided into pre-gestational and gestational DM. Pre-gestational diabetes may already be diagnosed by the primary care physician or at the first prenatal visit. Patients with one or more risk factors (BMI>30, prior GDM, PCOS, history of impaired glucose resistance) should probably be screened early.
Epidemiology: Gestational Diabetes Mellitus (GDM) is present in 6-7% of all pregnancies in the United States. Prevalence varies widely between ethnic groups with African Americans and Hispanics among the highest, and Caucasians having the lowest rates. Overall, the epidemiological pattern follows that of Diabetes Mellitus, type-2. Prevalence is increasing, possibly tied to increasing maternal age and mean weight.
Pathophysiology: GDM is similar to DM-2 in that there is increased insulin resistance, rather than decreased secretion by pancreatic beta cells. The exact mechanism of GDM is not fully known, however there are proposed mechanisms consistent with current understanding of pregnancy physiology.
By the second trimester, increased insulin resistance is normal. This is thought to increase glucose supplied to the developing fetus. This resistance is likely mediated by increased adiposity during pregnancy and hormonal products from the placenta like progesterone, cortisol, and human placental lactogen seem to be likely culprits. Unlike normal pregnancy, in GDM the beta cell plasticity is inadequate to keep pace with increasing resistance. It is not known why some women are able to overcome this resistance while others are not, but the mechanisms mirror that of Pre-gestational DM; autoimmunity against beta cells, single gene mutations, underlying obesity, etc.
Consequences: GDM is associated with multiple maternal and fetal complications including preeclampsia, hydramnios, macrosomnia/LGA, fetal cardio- and hepatomegaly, maternal and fetal birth trauma including shoulder dystocia, perinatal mortality, neonatal respiratory distress. Complications correlate to increasing blood glucose levels.
Preconception counseling should be considered for women with known preexistent diabetes mellitus attempting to become pregnant. Congenital malformations are two to four times more common in the setting of hyperglycemia at organogenesis, including caudal regression/dysplasia. Prematurity and miscarriage are also significantly increased in both pre-GDM and GDM.
Diagnosis: Currently, universal screening is commonly recommended in the United States. Glycohemoglobin (HbA) is not clinically useful for the surveillance of GDM, but a baseline at the first prenatal visit may be useful in establishing overt glucose intolerance/DM. The American College of Obstetrics and Gynecology recommend a two step screen and diagnosis approach:
Step One: Patient to take a 50g oral glucose dose (typically hyperosmolar solution), regardless of time of day (random, non-fasting). After one hour, venous blood is drawn and tested for glucose concentration. A positive result, indicating further diagnosis is concentration of 135 or greater in higher risk patients or 140 or greater in lower risk patients.
Step Two: On a positive result for step one, proceed to measure fasting glucose; then give 100g oral glucose load. Serum glucose is then measured at one, two, and three hours. A positive test is elevated values at two or more time points. (Carpenter/Coustan: fasting >95mg/dL, 1hr >180mg/dL, 2hr >155, 3hr >140; NDDG: fasting >105mg/dL, 1hr >190mg/dL, 2hr >165, 3hr >145).
Management: As with diabetes in the wider population, management of GDM may be broadly divided into three categories: diet, surveillance, pharmacology
Diet: If possible, patients should be referred to a registered dietician for nutritional consultation. Dietary management has the goals of achieving normoglycemia, preventing ketosis, providing for adequate weight gain during pregnancy, and contributing to fetal and maternal well-being. Typical meal plans would have 3 small-moderate sized meals and four snacks throughout the day. A low glycemic index is favored, with carbohydrates coming from fruits, vegetables and whole grains favored over flour based foods (white bread, pasta etc), 20% of daily calories coming from proteins, and 40% from fats.
Surveillance: Upon diagnosis of GDM or in pregnancy with overt DM, regular blood glucose monitoring is indicated. Current recommendations are for four times daily glucose measurements, logged and recorded. Recordings should be as consistent as possible, one fasting and the recordings with one or two hours after the first bite of each meal. There is currently no evidence to suggest benefit to reducing monitoring with demonstration of good glycemic control. Current ADA and ACOG glucose targets are <95 fasting, <141 1hr post-prandial, <121 2hrs post-prandial.
Pharmacoloy: Diet alone is sometimes not adequate for maintaining glycemic target levels. Additionally, there is controversy regarding the efficacy of diet alone in minimizing macrosomia. Insulin therapy, even in patients with normoglycemia, may be appropriate to limit LGA/macrosomia and can be started if there is ultrasound evidence of large abdominal girth. The favored approach is to titrate a simpler regimen of intermediate and rapid acting insulin. Lispro and Aspart are rapid acting preparations with demonstrated safety, and have lower risk of postprandial hypoglycemia. Available data also demonstrate the safety of NPH for intermediate action. Long-acting analogs are believed likely safe and effective, but are not as well studied.
Oral anti-hyperglycemics are an option for patients who can not tolerate injection or who fail insulin therapy. Glyburide has been shown to be effective and has not shown an increase in neonatal hypoglycemia or congenital anomalies. Like insulin, glyburide must be balanced carefully with meals and snacks. Additionally, while evidence suggest safety, there are limited long-term studies of the effects on the child. Metformin appears to be safe for use in the second and third trimester. However, it does cross the placenta and it is not known if exposure is dangerous or not. Older sulfonylureas such as tolbutamide are not recommended due to risk of fetal hyper insulinemia.