Pioglitazone improves insulin resistance and decreases blood pressure in adult patients with congenital adrenal hyperplasia

Abstract

Context Patients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity. Objectives To assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles. Design Randomized placebo controlled crossover trial. Participants Twelve CAH patients and 12 body mass and age-matched control subjects. Intervention Sixteen-week treatment with pioglitazone (45 mg/day) or placebo. Main outcome measure Insulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles. Results CAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P =0.000, GIR in controls 46.2±23.4 μmol/kg per min, P <0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0±13.6 vs 127.0±14.9 mmHg, P <0.001, diastolic: 72.8±11.5 vs 77.4±12.6 mmHg, P <0.001). No changes in body fat distribution, lipid, and steroid profiles were observed. Conclusions CAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.