Thiazolidinediones improve β-cell function in type 2 diabetic patients

American Journal of Physiology - Endocrinology and Metabolism - Tập 292 Số 3 - Trang E871-E883 - 2007
Amalia Gastaldelli1, Ele Ferrannini, Yoshinori Miyazaki, Masafumi Matsuda, Andrea Mari, Ralph A. DeFronzo
1Diabetes Division, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.

Tóm tắt

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 β-cell function. The aim of this study was to determine whether TZD-induced improvement in glycemic control is associated with improved β-cell function. We studied 11 normal glucose-tolerant and 53 T2DM subjects [age 53 ± 2 yr; BMI 29.4 ± 0.8 kg/m2; fasting plasma glucose (FPG) 10.3 ± 0.4 mM; Hb A1c8.2 ± 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 mUm−2min−1) clamp with [3-3H]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 A1c, and insulin-mediated total body glucose disposal (Rd) and decreased mean plasma FFA during OGTT (all P < 0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [ΔISR(AUC)/Δglucose(AUC) ÷ IR] was significantly improved in all TZD-treated groups: +1.8 ± 0.7 (PIO + drug-naïve diabetics), +0.7 ± 0.3 (PIO + sulfonylurea-treated diabetics), and 0.7 ± 0.2 (ROSI + sulfonylurea-withdrawn diabetics) vs. −0.2 ± 0.3 in the two placebo groups ( P 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 Rdand inversely with decreased plasma glucose and FFA during the OGTT. In T2DM patients, TZD treatment leads to improved β-cell function, which correlates strongly with improved glycemic control.

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American Journal of Physiology - Endocrinology and Metabolism

Tập 292 Số 3

E871-E883

Thông tin tác giả