This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We plan to conduct a prospective randomized trial for the treatment of GDM with glyburide or insulin. The primary outcome is to determine if there is an improvement from baseline in insulin sensitivity and b cell response in women with gestational diabetes who have failed diet and exercise (GDMA2) treated with glyburide. A secondary outcome will be to determine if there is an improvement from baseline in insulin sensitivity and b cell response in women with GDMA2 treated with insulin. Gestational diabetes complicates 3-5% of all pregnancies. The goal of treatment is to prevent/minimize fetal morbidities including macrosomia, shoulder dystocia, hyperbilirubinemia and hypoglycemia. In order to attain this goal, strict glycemic control is necessary. When optimal glycemic control is not achieved with diet and exercise alone, standard treatment is insulin. Insulin therapy has several disadvantages: patient discomfort, inconvenience of injections, expense of supplies, patient compliance. An alternative to insulin, desirable for both patient and physician, is the use of an oral hypoglycemic agent. Glyburide has been used to treat gestational diabetes in several clinical studies, achieving good glycemic control. In the nonpregnant state, glyburide has been shown to increase insulin sensitivity. However, the mechanism of action in gestational diabetes is unknown. Furthermore, the effect on infant body composition and other metabolic markers associated with fetal adiposity is yet to be determined. All women meeting study criteria will be offered participation in the study to determine their insulin sensitivity prior to initiation and after 5 weeks of treatment. Maternal anthropometric measurements, nutrition and activity history will be collected at both intervals. At delivery, glyburide levels in maternal serum and umbilical cord blood will be measured in those receiving glyburide. All participants will have umbilical cord blood collected to evaluate other metabolic markers of fetal adiposity including leptin, C-peptide, free fatty acid. Infant body composition will be determined by anthropometric measurements within 48 hours of life. The randomization will include 108 women, 54 to each treatment group. The study has adequate power to detect a significant difference in the primary outcome evaluating a 30% increase in insulin sensitivity in the glyburide group, as well as 1st and 2nd phase beta cell response. Evaluation of neonatal body composition and metabolic markers affecting body composition will be descriptive in nature.
Showing the most recent 10 out of 426 publications
