Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus

Objective: The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus. Methods: In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C-peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals. Results: Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg x 100. Large artery elasticity tended to increase toward the end of the study (P = not significant). Systolic blood pressure decreased from 144 to 124 mm Hg and diastolic blood pressure decreased from 80 to 68 mm Hg, despite mild weight gain. Heart rate tended to decrease from 76.3 to 74.7 beats/min (P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm⁵. Plasma insulin, in patients not treated with insulin, decreased from 42.45 ± 24.90 to 27.86 ± 14.86 IU/mL (P = .0001). Conclusions: Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.