Objective: To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension, classified based on abnormalities of their renin-angiotensin system.
Research design and methods: A total of 24 hypertensive nondiabetic patients (age 58 +/- 6 years, BMI 30 +/- 5 kg/m2) were studied before and after rosiglitazone treatment. After 2 weeks off antihypertensive medication, subjects received a euglycemic-hyperinsulinemic clamp (40 mU. m(-2). min(-1)) with 6,6-[2H2]glucose infusion, ambulatory blood pressure monitoring, and blood tests for cardiovascular risk factors. Subjects were then placed on rosiglitazone (4 mg orally b.i.d.) and their usual antihypertensive medications (but not ACE inhibitors) for 16 weeks, and baseline tests were repeated.
Results: There was no change in fasting plasma glucose (83 +/- 2 vs. 82 +/- 2 mg/dl, P = 0.60), but fasting insulin decreased (16.1 +/- 1.4 vs. 12.5 +/- 0.9 micro U/ml, P < 0.01). Total glucose disposal during the clamp increased (5.0 +/- 0.4 vs. 5.9 +/- 0.5 mg. kg(-1). min(-1), P < 0.001), with no change in suppression of hepatic glucose output. There were significant decreases in mean 24-h systolic (138 +/- 2 vs. 134 +/- 2 mmHg, P < 0.02) and diastolic (85 +/- 2 vs. 80 +/- 2 mmHg, P < 0.0001) blood pressure, and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity (r = 0.59, P < 0.005). Triglycerides (135 +/- 16 vs. 89 +/- 8 mg/dl, P < 0.01), LDL cholesterol (129 +/- 6 vs. 122 +/- 8 mg/dl, P = 0.18), and HDL cholesterol (51 +/- 3 vs. 46 +/- 3 mg/dl, P < 0.02) all decreased, with no change in the LDL-to-HDL ratio. Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly.
Conclusions: Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity, reduces systolic and diastolic blood pressure, and induces favorable changes in markers of cardiovascular risk. Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension.