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At a glance
|Would you consider glyburide as an alternative therapy to insulin for women with gestational diabetes?|
Gestational diabetes mellitus (GDM) is a common medical complication of pregnancy and a growing problem worldwide. The condition is defined as glucose intolerance (of variable degree) with onset or first recognition in pregnancy.1
It is estimated that GDM affects about 200,000 (7%) of the more than 4 million births annually1 and is associated with higher rates of such adverse neonatal outcomes as macrosomnia, neonatal hypoglycemia, shoulder dystocia, and brachial plexus injuries.2 In addition, infants who are born with extreme macrosomia may be predisposed to developing glucose intolerance or GDM as adults.2
Glyburide (Diabeta, Glycron, Glynase, Micronase) is a second-generation sulfonylurea used in the treatment of diabetes. It lowers blood glucose levels by stimulating the excretion of endogenous insulin from beta cells in the pancreas.3
At this time, oral hypoglycemic agents have not been approved for the treatment of GDM, and insulin continues to be the only recommended agent to lower glucose levels in pregnant women.4 However, acceptance of the use of glyburide in management of GDM has been growing. The question that must be answered is, is glyburide a clinically effective alternative to insulin therapy in GDM?
GDM most commonly occurs early in the third trimester of pregnancy as a result of metabolic changes.5 Critical anabolic hormones responsible for fetal growth and development increase dramatically in the final 20 weeks of gestation.
These hormones mobilize the woman’s nutritional resources — primarily glucose — making them available to the fetus. This increase in glucose mobilization occurs along with a decrease in insulin sensitivity from human placental lactogen, a placental hormone with strong anti-insulin and lipolytic effects.6 Peripheral insulin sensitivity during the third trimester decreases to 50% of that seen in the first trimester, and despite higher insulin levels, basal hepatic glucose output is 30% higher.6
Glucose intolerance is the result of the combination of late-pregnancy hormones and a chronic form of insulin resistance that was present before but exacerbated by pregnancy. It is thought that pregnancy unmasks the onset of beta-cell dysfunction that was present before conception.7
Fasting and preprandial glucose values are lower during pregnancy in both diabetic and nondiabetic women. Euglycemia is considered to be 60-70 mg/dL while fasting and <120 mg/dL two hours after meals.5
Keep in mind that 50% of women present with glucosuria at some point during pregnancy as a result of increased glomerular filtration rate and glucose load presented to the kidneys.8 Because such other symptoms as increased urination and thirst may also be normal findings in pregnancy, the diagnosis of GDM may be overlooked without careful screening.4
The diabetes risk assessment should be performed at the first prenatal visit. Women that are considered at high risk have one or more of the following: severe obesity, a strong family history of type 2 diabetes, impaired glucose metabolism, polycystic ovarian syndrome, or a history of GDM or delivery of large-for-gestational-age (LGA) infant.7
Patients are diagnosed via the glucose challenge test, a two-step approach using an initial screening measuring plasma or serum glucose one hour after a 50-g oral glucose load. If the plasma glucose is >140 mg/dL (7.8 mmol/L), an oral glucose tolerance test (OGTT) should be performed.
The OGTT is administered over the course of three hours with either a 100- or 75-g load of glucose.5 GDM is confirmed if two or more of the findings listed in Table 1 are present in venous plasma after an overnight fast (8-14 hours).5