Effect of peroxisome proliferator-activated receptor gamma agonist treatment on subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes.
OBJECTIVE
To determine the effect of thiazolidinedione treatment on subclinical atherosclerosis progression in insulin-requiring patients with clinical characteristics suggesting type 2 diabetes.


METHODS
Eligible participants (n = 299) were randomized within strata of baseline common carotid artery (CCA) intima-media thickness (IMT) (<0.8 mm, >or=0.8 mm) to 400 mg troglitazone daily or placebo for 2 years. A general linear mixed-effects model was used to compare the rate of change in CCA-IMT between treatment groups.


RESULTS
Overall, average rates of CCA-IMT change were not significantly different between troglitazone- and placebo-treated subjects (0.0030 +/- 0.021 vs. 0.0066 +/- 0.021 mm/year; P = 0.17). In the stratum of subjects with CCA-IMT >or=0.8 mm, troglitazone significantly reduced the progression of CCA-IMT relative to placebo (0.0013 +/- 0.022 vs. 0.0084 +/- 0.023 mm/year; P = 0.03). Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01). Whereas blood pressure significantly differed between treatment groups in the >or=0.8-mm stratum, there was no difference between treatment groups in the <0.8-mm stratum.


CONCLUSIONS
Insulin sensitization and reduction in blood pressure may be contributory mechanisms by which troglitazone reduced subclinical atherosclerosis progression in this cohort of well-controlled insulin-dependent patients with clinical characteristics suggesting type 2 diabetes.
Hodis
Howard N
HN
Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, 90033, USA. athero@usc.edu
Mack
Wendy J
WJ
Zheng
Ling
L
Li
Yanjie
Y
Torres
Mina
M
Sevilla
Diego
D
Stewart
Yolanda
Y
Hollen
Barbara
B
Garcia
Karla
K
Alaupovic
Petar
P
Buchanan
Thomas A
TA
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D002839:Chromans / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000077288:Troglitazone
D002839:Chromans; D007328:Insulin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077288:Troglitazone