Thiazolidinediones improve β-cell function in type 2 diabetic patients

被引:157
作者
Gastaldelli, Amalia
Ferrannini, Ele
Miyazaki, Yoshinori
Matsuda, Masafumi
Mari, Andrea
DeFronzo, Ralph A.
机构
[1] Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, San Antonio, TX 78229 USA
[2] Univ Pisa, Sch Med, Dept Internal Med, Metab Unit, I-56100 Pisa, Italy
[3] CNR, Inst Clin Physiol, Pisa, Italy
[4] CNR, Inst Biomed Engn, Padua, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2007年 / 292卷 / 03期
关键词
type; 2; diabetes; insulin secretion; insulin secretion/insulin resistance index;
D O I
10.1152/ajpendo.00551.2006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 +/- 2 yr; BMI 29.4 +/- 0.8 kg/m(2); fasting plasma glucose (FPG) 10.3 +/- 0.4 mM; Hb A(1c) 8.2 +/- 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 mU (.) m(-2) (.) min(-1)) clamp with [3-H-3] 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(1c), and insulin-mediated total body glucose disposal (R-d) and decreased mean plasma FFA during OGTT (all P < 0.01, ANOVA). The insulin secretion/insulin resistance (disposition) index [Delta ISR(AUC)/Delta glucose(AUC) divided by IR] was significantly improved in all TZD-treated groups: +1.8 +/- 0.7 (PIO + drug-naive diabetics), +0.7 +/- 0.3 (PIO + sulfonylurea-treated diabetics), and 0.7 +/- 0.2 (ROSI +/- sulfonylurea-withdrawn diabetics) vs. -0.2 +/- 0.3 in the two placebo groups (P 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 R-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.
引用
收藏
页码:E871 / E883
页数:13
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