Diabetes is associated with stiff large arteries, which plays an important role in the pathogenesis of vascular disease (1) and is the primary cause of mortality and morbidity with type 2 diabetes. Similarly, after menopause, women experience a dramatic increase in large artery stiffness and the rate of cardiovascular disease (2). Thiazolidinediones modulate glucose homeostasis (3) and exhibit a number of potential antiatherogenic actions (3), the collective effects of which remain to be fully elucidated in humans.
We therefore investigated whether rosiglitazone, the second member of the thaizolidinediones group, would improve blood pressure and arterial compliance, measured by distensibility index (4), in postmenopausal women with type 2 diabetes. In a randomized, double-blind, placebo-controlled study, 31 women with established diabetes diagnosed 1–12 years prior were tested before and after 12 weeks of treatment with 4 mg rosiglitazone daily (n = 21) or matching placebo (n = 10). Eighty percent of the women continued their use of metformin, a sulfonyurea, or both throughout the trial. Glycemic control, lipids, blood pressure, and distensibility index were assessed. Rosiglitazone reduced fasting plasma glucose (from 9.40 ± 1.7 to 7.1 ± 0.9 mmol · l−1 · l−1, mean ± SEM; P = 0.001), HbA1c (from 7.6 ± 0.7 to 6.4 ± 0.4%; P = 0.001), brachial systolic blood pressure (from 124 ± 10 to 112 ± 9 mmHg; P = 0.003), central systolic blood pressure (from 118 ± 9 to 111 ± 7 mmHg; P = 0.02), diastolic blood pressure (from 71 ± 4 to 65 ± 3 mmHg; P = 0.004) and mean arterial pressure (from 91 ± 6 to 84 ± 4 mmHg; P = 0.001), while lipid levels were unchanged. Rosiglitazone increased distensibility index (from 0.106 ± 0.02 to 0.134 ± 0.03 arbitrary compliance units; P = 0.01) and reduced pulse pressure (from 54 ± 7 to 50 ± 7 mmHg; P = 0.08). There were no significant changes in lipid profiles with rosiglitazone treatment. The placebo had no effect on any of the variables measured. All women maintained >90% compliance with no adverse events reported.
The main findings of this study are that for postmenopausal women with type 2 diabetes rosiglitazone improves glycemic control, reduces blood pressure, and increases compliance of large proximal arteries. Strict glycemic control delays the onset and moderates the progression of vascular complications (5), which may in part explain the increases in arterial compliance and reductions in blood pressure with rosiglitazone; however, it is possible that rosiglitazone improves cardiovascular parameters independently of glycemic changes. A reduction in blood pressure and an increase in large proximal artery compliance may reduce the risk of coronary artery disease (1). Long-term studies are required to determine whether these observed effects are sustained. In conclusion, rosiglitazone is an effective treatment to improve glycemic control and reduce the risk of cardiovascular disease in postmenopausal women with type 2 diabetes.
