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Effect of Troglitazone on B Cell Function, Insulin Sensitivity, and Glycemic Control in Subjects with Type 2 Diabetes Mellitus¹

Division of Metabolism, Endocrinology, and Nutrition and Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington 98108

Address all correspondence and requests for reprints to: Ronald L. Prigeon, M.D., Veterans Administration Puget Sound Health Care System (151), 1660 South Columbian Way, Seattle, Washington 98108.

We studied the effects of troglitazone (200–800 mg daily) or placebo on carbohydrate metabolism in 18 subjects with type 2 diabetes (mean age, 66 yr; body mass index, 27.7 kg/m²) at baseline and after taking medication for 12 weeks. We measured fasting proinsulin (PI) and immunoreactive insulin (IRI) levels in all subjects. Thirteen subjects underwent additional metabolic studies, including injection of arginine to determine the acute insulin response, and an iv glucose tolerance test to measure the insulin sensitivity index (S_I) and glucose effectiveness at zero insulin using the minimal model, iv glucose tolerance, and acute insulin response to glucose. Troglitazone treatment resulted in a decrease in fasting plasma glucose from 11.2 ± 0.7 to 9.6 ± 0.9 mmol/L (P = 0.02). This was associated with a decrease in the fasting IRI concentration (111 ± 20 to 82 ± 13 pmol/L; P = 0.02) and a trend toward a decrease in the fasting PI concentration (43 ± 11 to 25 ± 4 pmol/L; P = 0.06). A significant decrease in PI/IRI was observed (38.3 ± 3.6% to 32.6 ± 3.2%; P = 0.04). Troglitazone therapy was also associated with a decrease in the acute insulin response to arginine (226 ± 34 to 167 ± 25 pmol/L; P = .01) and a near-significant percent increase in S_I (75 ± 35%; P = 0.06). Glucose effectiveness at zero insulin, iv glucose tolerance, and acute insulin response to glucose did not change. Thus, we found that the decrease in plasma glucose during troglitazone therapy is associated with a dose-related decrease in PI/IRI and an increase in S_I, suggesting that changes in both B cell function and insulin sensitivity contribute to the improvement in metabolic status.

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