Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study.
OBJECTIVE
Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima-media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS).


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Malmö University Hospital, Malmö, Sweden.


METHODS
555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35-80 years. 447 subjects (165 T2DM and 282 IRS) completed the study.


METHODS
Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily.


METHODS
Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables.


RESULTS
There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: -0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9.


CONCLUSIONS
In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS.
Hedblad
B
B
Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. bo.hedblad@med.lu.se
Zambanini
A
A
Nilsson
P
P
Janzon
L
L
Berglund
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000188:drug therapy*; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013548:Sweden; D045162:Thiazolidinediones / Q000627:therapeutic use*; D017539:Tunica Intima / Q000473:pathology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone