The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes.

OBJECTIVES: The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation. Although the factors that contribute to the development of type 2 diabetes are complex and not wholly elucidated, the triad of severe obesity, hyperinsulinemia, and a family history of type 2 diabetes places a child at an increased risk for development of the disease. Current approaches to the prevention of type 2 diabetes, including dietary counseling and exercise, have had limited success. We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients. To that end, we conducted a double-blind, placebo-controlled study of the effects of metformin on body mass index (BMI), serum leptin, glucose tolerance, and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. METHODS: The study population consisted of 29 white and black adolescents aged 12 to 19 years. All had BMIs exceeding 30 kg/m(2). Criteria for enrollment included: 1) a fasting insulin concentration exceeding 15 microU/mL; and 2) at least 1 first- or second-degree relative with type 2 diabetes. All patients had fasting plasma glucose concentrations <110 mg% and hemoglobin A1c concentrations

Combination insulin and sulfonylurea therapy in insulin-requiring type 2 diabetes mellitus.

PURPOSE: To determine the effect(s) on glucose control, insulin dose, and circulating insulin levels of the addition of a sulfonylurea (glipizide) to the treatment regimen of patients with insulin-requiring type 2 diabetes mellitus. PATIENTS AND METHODS: Thirty seven patients with type 2 diabetes mellitus taking insulin for at least 1 year prior to study and treated with > or = 40 U of insulin per day were recruited for a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with 3 months of insulin + placebo (I + P) and 3 months of insulin + glipizide (I + G), with an intermediate 1 month washout period using insulin therapy alone. Adjustments were made initially to the maximum dose of glipizide (40 mg/day), followed by insulin dose adjustments. Twenty-nine of the 37 patients demonstrated a significant C-peptide response to Ensure and were selected for analysis. RESULTS: The fasting plasma glucose in the I + G arm was 6.8 (121.8 mg/dl) vs. 8.7 mmol/L (156.0 mg/dl) in the I + P arm, P < 0.001. Mean plasma glucose over 24 hours was 9.8 (176.9 mg/dl) for I + G vs. 11.3 mmol/L (203.8 mg/dl) for I + P, P < 0.001. Glycated hemoglobin was significantly different (9.8 I + G vs. 11.4% I + P, P < 0.008). The total daily insulin dose required was significantly lower with I + G (69.1 vs. 87.3 U, P < 0.0005). However, there were no significant differences in free insulin levels. CONCLUSION: The addition of a sulfonylurea (glipizide) to insulin therapy in patients with insulin-requiring type 2 diabetes mellitus taking large doses of insulin results in a rapid and substantial improvement in glucose control despite a significant reduction in insulin dose. Therefore, this form of combination therapy should be considered for patients with the above characteristics whose diet and exercise programs are correct but whose response to insulin therapy is inadequate.