Thiazolidinediones improve [beta]-cell function in type 2 diabetic patients

Thiazolidinediones (TZDs) improve glycemic control and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). There is growing evidence from in vivo and in vitro studies that TZDs improve pancreatic [beta]-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved [beta]-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53 [+ or -] 2 yr; BMI 29.4 [+ or -] 0.8 kg/[m.sup.2]; fasting plasma glucose (FPG) 10.3 [+ or -] 0.4 raM; Hb [A.sub.1c] 8.2 [+ or -] 0.3%]. Diabetic patients were randomized to receive placebo or TZD for 4 mo. Subjects received 1) 2-h OGTT with determination of plasma glucose, insulin, and C-peptide concentrations and 2) two-step euglycemic insulin (40 and 160 mU*[m.sup.-2]*[min.sup.-1]) clamp with [3-[sup.3]H]glucose. T2DM patients were then randomized to receive 4 mo of treatment with pioglitazone (45 mg/day), rosiglitazone (8 mg/day), or placebo. Pioglitazone and rosiglitazone similarly improved FPG, mean plasma glucose during OGTT, Hb [A.sub.1c], and insulin-mediated total body glucose disposal ([R.sub.d]) and decreased mean plasma FFA during OGTT (all P < 0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [[DELTA]ISR([DELTA]UC)/Aglucose(AUC)/IR] was significantly improved in all TZD-treated groups: +1.8 [+ or -] 0.7 (PIO + drug-naive diabetics), +0.7 [+ or -] 0.3 (PIO + sulfonylurea-treated diabetics), and 0.7 [+ or -] 0.2 (ROSI + sulfonylurea-withdrawn diabetics) vs. -0.2 [+ or -] 0.3 in the two placebo groups (P < 0.01, all TZDs vs. placebo, ANOVA). Improved insulin secretion correlated positively with increased body weight, fat mass, and [R.sub.d] and inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved [beta]-cell function, which correlates strongly with improved glycemic control. type 2 diabetes; insulin secretion; insulin secretion/insulin resistance index