Losartan Elevates the Serum High-Molecular Weight-Adiponectin Isoform and Concurrently Improves Insulin Sensitivity in Patients with Impaired Glucose Metabolism

Abstract

Adiponectin is an adipocyte hormone that ameliorates insulin resistance and prevents diabetes. Patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are at a high risk of developing diabetes and cardiovascular diseases. Since treatment with angiotensin II receptor blockers retards the development of diabetes, the effects of losartan on serum adiponectin levels were examined with regard to insulin sensitivity in pre-diabetic patients. Sixty-five patients with IFG/IGT (42 males, 23 females, 63+/-13 years old) were randomized to receive 25-100 mg of losartan (n=33) or a calcium channel blocker (CCB, n=32) for 3 months. Before and after the treatment, changes in blood pressure, insulin sensitivity (HOMA-R) and serum concentrations of high molecular weight (HMW)-adiponectin and free fatty acid (FFA) were assessed. At baseline, the HMW-adiponectin concentration negatively correlated with the patient's body mass index, HOMA-R and triglyceride levels, and positively correlated with high-density lipoprotein (HDL)-cholesterol levels. However, the HMW-adiponectin concentration showed no correlation with blood pressure. HMW-adiponectin concentrations were similar between the losartan group and the CCB group. Both the losartan and CCB treatments similarly and significantly reduced the mean blood pressure (107+/-7 mmHg to 95+/-7 mmHg, p<0.0001, and 104+/-6 mmHg to 93+/-9 mmHg, p<0.0001, respectively). Losartan treatment resulted in a significant increase in HMW-adiponectin concentrations (45.9%) and a significant decrease in HOMA-R (23.9%) and FFA concentrations (26.5%); the percent changes were greater than those induced by CCB treatment (p<0.001, p<0.05 and p<0.01, respectively). We conclude that losartan increases the serum HMW-adiponectin concentration and concurrently improves insulin sensitivity in subjects with IFG/IGT. These results suggest that losartan may prevent diabetes by increasing serum adiponectin levels.