Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

Abstract

Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance.

To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension.

In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters.

Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 ± 2.6 to 41.9 ± 3.2 μmol/min per kg per nmol/l, P< 0.001) and the HOMA-IR index significantly decreased (6.34 ± 0.39 versus 4.40 ± 0.33, P< 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 ± 1.8 versus 129.9 ± 1.7 mmHg, P< 0.001 for systolic BP and 76.0 ± 1.6 versus 71.9 ± 1.6 mmHg, P< 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = −0.78, P< 0.01 and r = −0.68, P< 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 ± 0.41 versus 7.55 ± 0.31 mmol/l, P< 0.001), insulin (94.0 ± 0.41 versus 79.5 ± 5.6 pmol/l, P< 0.01) and HbA1c (8.15 ± 0.24 versus 7.24 ± 0.19%, P< 0.001).

Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.