Rosiglitazone improves insulin sensitivity and glucose tolerance in subjects with impaired glucose tolerance.
OBJECTIVE
This study was designed to evaluate the effects of rosiglitazone (ROS) on insulin sensitivity, beta-cell function, and glycaemic response to glucose challenge and meal in subjects with impaired glucose tolerance (IGT).


METHODS
Thirty patients with IGT (ages between 30 and 75 years and BMI (body mass index) < or = 27 kg/m2) were randomly assigned to receive either placebo (n = 15) or ROS (4 mg/day) (n = 15). All participants underwent a 75-g oral glucose tolerance test (OGTT), meal test, and frequently sampled intravenous glucose tolerance test (FSIGT) before and after the 12-week treatment.


RESULTS
After 12 weeks of ROS treatment, there were significant increases in total cholesterol (TC) (4.25 +/- 0.22 vs 4.80 +/- 0.17 mmol/l, P < 0.001), high-density lipoprotein cholesterol (HDL-C) (1.25 +/- 0.07 vs 1.43 +/- 0.06 mmol/l, P < 0.05), and low-density lipoprotein cholesterol (LDL-C) (2.70 +/- 0.15 vs 3.37 +/- 0.17 mmol/l, P < 0.05) without changes in triglyceride concentration, TC/HDL-C and LDL-C/HDL-C ratio. Although the acute insulin response (AIR) to intravenous glucose and disposition index (measured as the ability of pancreatic beta-cell compensation in the presence of insulin resistance) remained unchanged, the insulin sensitivity (SI) and glucose effectiveness (SG) were remarkably elevated (0.38 +/- 0.06 vs 0.54 +/- 0.09 x 10(-5) min(-1)/pmol, P < 0.05; 0.017 +/- 0.002 vs 0.021 +/- 0.001 min(-1), P < 0.05, respectively) in the ROS group. The glucose, insulin, and c-peptide areas under curve (AUC) in response to OGTT and the glucose and insulin AUC during meal were significantly ameliorated in the ROS group. Five out of 15 (33%) and two out of 15 (13%) subjects treated with ROS and placebo, respectively, reversed to normal response during OGTT (P < 0.05).


CONCLUSIONS
Rosiglitazone treatment significantly improved insulin resistance and reduced postchallenge glucose and insulin concentrations in patients with impaired glucose tolerance without remarkable effects on beta-cell secretory function.
Hung
Yi-Jen
YJ
Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. metahung@yhaoo.com
Hsieh
Chang-Hsun
CH
Pei
Dee
D
Kuo
Shi-Wen
SW
Lee
Jiunn-Tay
JT
Wu
Ling-Yi
LY
He
Chih-Tsueng
CT
Lee
Chien Hsing
CH
Fan
Sandra Chyi
SC
Sheu
Wayne Huey-Herng
WH
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D016009:Chi-Square Distribution; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D012737:Sex Factors; D016037:Single-Blind Method; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone