PMID- 17106061
OWN - NLM
STAT- MEDLINE
DCOM- 20070413
LR  - 20220408
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 292
IP  - 3
DP  - 2007 Mar
TI  - Thiazolidinediones improve beta-cell function in type 2 diabetic patients.
PG  - E871-83
AB  - 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/m2; 
      fasting plasma glucose (FPG) 10.3+/-0.4 mM; Hb A1c 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-(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 
      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 [DeltaISR(AUC)/Deltaglucose(AUC)/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      (ROSI+sulfonylurea-withdrawn diabetics) vs. -0.2+/-0.3 in the two placebo groups 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 Rd 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.
FAU - Gastaldelli, Amalia
AU  - Gastaldelli A
AD  - Diabetes Division, Department of Medicine, University of Texas Health Science 
      Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
FAU - Ferrannini, Ele
AU  - Ferrannini E
FAU - Miyazaki, Yoshinori
AU  - Miyazaki Y
FAU - Matsuda, Masafumi
AU  - Matsuda M
FAU - Mari, Andrea
AU  - Mari A
FAU - DeFronzo, Ralph A
AU  - DeFronzo RA
LA  - eng
GR  - DK-24092/DK/NIDDK NIH HHS/United States
GR  - M01-RR-01346/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20061114
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Insulin)
RN  - 0 (Placebos)
RN  - 0 (Thiazolidinediones)
SB  - IM
MH  - Body Composition
MH  - Body Weight
MH  - Diabetes Mellitus, Type 2/drug therapy/*metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Glucose Clamp Technique
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/*drug effects/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Placebos
MH  - Thiazolidinediones/*pharmacology
EDAT- 2006/11/16 09:00
MHDA- 2007/04/17 09:00
CRDT- 2006/11/16 09:00
PHST- 2006/11/16 09:00 [pubmed]
PHST- 2007/04/17 09:00 [medline]
PHST- 2006/11/16 09:00 [entrez]
AID - 00551.2006 [pii]
AID - 10.1152/ajpendo.00551.2006 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E871-83. doi: 
      10.1152/ajpendo.00551.2006. Epub 2006 Nov 14.