Angiotensin II type 1 receptor blockers (ARBs) are widely used in the treatment of hypertension and have been shown to restore impaired intracellular insulin signaling and reduce the incidence of type 2 diabetes (1–3). Telmisartan has a unique property that activates peroxisome proliferator-activated receptor-γ (PPAR-γ) (4–6). We studied the effect of this unique property of telmisartan on insulin resistance and circulating levels of adiponectin and highly sensitive C-reactive protein (hs-CRP) in hypertensive patients with type 2 diabetes.
The study comprised 18 participants with hypertensive type 2 diabetes (9 men and 9 women) aged 36–79 years (64 ± 12, mean ± SD) and treated with valsartan (80 mg/day, n = 11) or candesartan (8 mg/day, n = 7) for >6 months. None of the changes in clinical and biochemical findings occurred in the subjects during this period. Then, telmisartan (40 mg/day) was administered instead of the ARBs for 12 weeks. Fifteen subjects were treated with antidiabetic agents (13 sulfonylurea, 2 nateglinide) and 3 with diet therapy alone. There were no changes in diet and other medications. No subject received glitazone and insulin. Statistical analysis was performed using Wilcoxon’s matched-pair signed-rank test.
Neither systolic nor diastolic blood pressure were significantly changed. Telmisartan treatment resulted in a significant decrease in fasting insulin level (10.7 ± 3.8 to 8.6 ± 2.7 mU/l, P < 0.01), although decreases in fasting plasma glucose (132.5 ± 55.1 to 126.5 ± 39.3 mg/dl) and HbA1c (6.89 ± 0.89 to 6.79 ± 0.96%) were not statistically significant. Serum triglyceride levels were significantly reduced from 133.6 ± 51.1 to 118.7 ± 48.1 mg/dl, (P < 0.05). Mild improvements in total and HDL cholesterol were also observed after treatment (total cholesterol 197.2 ± 28.2 to 190.5 ± 30.5 mg/dl HDL cholesterol from 47.6 ±11.2 to 48.5 ±12.1 mg/dl). Serum adiponectin was significantly increased (6.95 ± 2.91 to 7.97 ± 3.48 μg/ml, P < 0.005), and hs-CRP was decreased (0.154 ± 0.155 to 0.109 ± 0.120 mg/dl, P < 0.05). This study also demonstrated the reciprocal association between adiponectin and hs-CRP (r = −0.53, P < 0.01). Body weight gain and edema never developed.
Adiponectin and hs-CRP are closely related to insulin resistance and development of atherosclerosis (6,7). Our results indicated that telmisartan has beneficial effects on the risk factors for cardiovascular disease, which is a major concern in the treatment of type 2 diabetes. Since all subjects were already treated with ARBs and blood pressure was not changed, the majority of our results were not produced by the further suppression of the rennin-angiotensin system. Our observation in this study is consistent with recent reports that telmisartan, not valsartan, activates PPAR-γ (8). Also, our results are in agreement with recent clinical reports that telmisartan improved insulin resistance or glycemic control (9,10).
Our present findings demonstrate that telmisartan has additional effects on insulin sensitivity and antiatherosclerosis, probably via its effects on PPAR-γ. These findings offer a new idea for the drug targeted to defend against type 2 diabetes with accompanying metabolic disorders.
