EFFECT OF TROGLITAZONE ON B-CELL FUNCTION, INSULIN SENSITIVITY, AND GLYCEMIC CONTROL IN SUBJECTS WITH TYPE-2 DIABETES-MELLITUS

We studied the effects of troglitazone (200-800 mg daily) or placebo o n carbohydrate metabolism in 18 subjects with type 2 diabetes (mean ag e, 66 yr; body mass index, 27.7 kg/m(2)) at baseline and after taking medication for 12 weeks. We measured fasting proinsulin (PI) and immun oreactive insulin (IRI) levels in all subjects. Thirteen subjects unde rwent additional metabolic studies, including injection of arginine to determine the acute insulin response, and an iv glucose tolerance tes t to measure the insulin sensitivity index (S-I) and glucose effective ness at zero insulin using the minimal model, iv glucose tolerance, an d acute insulin response to glucose. Troglitazone treatment resulted i n 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 fastin g IRI concentration (111 +/- 20 to 82 +/- 13 pmol/L; P = 0.02) and a t rend toward a decrease in the fasting PI concentration (43 +/- 11 to 2 5 +/- 4 pmol/L; P = 0.06). A significant decrease in PI/IRI was observ ed (38.3 +/- 3.6% to 32.6 +/- 3.2%; P = 0.04). Troglitazone therapy wa s also associated with a decrease in the acute insulin response to arg inine (226 +/- 34 to 167 +/- 25 pmol/L; P = .01) and a near-significan t percent increase in S-I (75 +/- 35%; P = 0.06). Glucose effectivenes s at zero insulin, iv glucose tolerance, and acute insulin response to glucose did not change. Thus, we found that the decrease in plasma gl ucose during troglitazone therapy is associated with a dose-related de crease in PI/IRI and an increase in S-I, suggesting that changes in bo th B cell function and insulin sensitivity contribute to the improveme nt in metabolic status.