Glyburide, exercise moderate gestational diabetes

OB/GYN News, Nov 1, 2001 by Bruce Jancin

STANFORD, CALIF. -- Diet and insulin are no longer the only tools available for the management of gestational diabetes mellitus, Dr. Judy E. Kalinyak said at a conference on perinatal and pediatric nutrition.

They've been joined by exercise and the second-generation oral sulfonylurea agent glyburide. And further down the line is the prospect of treating gestational diabetes with nateglinide (Starlix), an oral agent released last December that addresses the postprandial hypoglycemia lying at the heart of the problem, but for which no safety studies in pregnancy exist, explained Dr. Kalinyak, an endocrinologist at Stanford (Calif.) University.

Exercise is remarkably effective therapy in couch potatoes with gestational diabetes. When contracting, skeletal muscle increases its glucose uptake 35 times. Exercise also increases insulin sensitivity and reduces intracellular triglyceride levels, she said at the meeting, which was also jointly sponsored by Symposia Medicus and Stanford University

A few caveats regarding exercise: "We want minimal exertion because you end up with increased risk of genetic defects when basal body temperature climbs above 38[degrees]C--you get your heat shock proteins turned on at that point. But that takes at least 15-20 minutes or more of strenuous exercise.

There is also an increased injury risk inherent in encouraging exercise at a time of pregnancy-induced connective tissue laxity and joint instability in women with little exercise experience and a center of balance that shifts almost daily.

Glyburide was recently shown to achieve the same degree of glycemic control as insulin in a major randomized study involving 404 women with gestational diabetes. This comparison of glyburide and insulin therapy was conducted by Dr. Oded Langer and associates at St. Luke's-Roosevelt Hospital Center, New York.

Perinatal outcomes were the same between groups, too. These included similar rates of macrosomia, neonatal hypoglycemia, neonatal ICU admission, lung problems and need for ventilatory support, fetal anomalies, and mortality (N. Engl. J. Med. 343[16]:1134-8, 2000). In an earlier study, Dr. Langer established that glyburide doesn't cross the placenta, unlike first-generation oral sulfonylureas.

The availability of an oral alternative to insulin for women with gestational diabetes is an extremely important development because it's likely to dramatically improve compliance with therapy. But Dr. Kalinyak isn't yet ready to make wholesale changes in her clinical practice.

"Most practicing endocrinologists are going to want to see a little bit more data on glyburide from comprehensive studies, which are currently underway before making a dramatic change," she said.

With regard to insulin, the focus in gestational diabetes is on short-acting coverage of postprandial glucose excursions. These women typically have enough pancreatic function that long-acting insulin need be added only in the third trimester.

Today Dr. Kalinyak typically uses regular insulin for short action and NPH as her longer-acting product in pregnancy "A year from now, when more safety data in pregnancy are available, we might be talking about Humalog-glargine regimens," she continued.

Nateglinide is quite similar to Humalog insulin in its rapid onset of action and short half-life. "We're using it a lot in early-onset type 2 diabetic patients, where we're really treating postprandial hyperglycemia, which has been linked to increased risk of cardiovascular disease," Dr. Kalinyak said. If it can be established that nateglinide doesn't cross the placenta, this will become a popular therapy in gestational diabetes, she predicted.