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 28.5G11.6 to 38.9G11.0 mmol/kg per min, PZ0.000, GIR in controls 46.2G23.4 mmol/kg per min, P!0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0G13.6 vs 127.0G14.9 mmHg, P!0.001, diastolic: 72.8G11.5 vs 77.4G12.6 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.

Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Our patients had increased insulin release during the OGTT and older patients tended to have higher HbA1c than younger ones, suggesting an increased risk of T2DM in the older CAH males. Insulin resistance has been found in adult CAH by all investigators (6,8,9,12,13,18,(20)(21)(22)(23), but one (18) and has most commonly been expressed as homeostasis model assessment (HOMA) index. We did not calculate this index because fasting glucose was low in our patients, which may lead to a falsely low estimation of insulin resistance.…”

“…Inadequate mineralocorticoid therapy for aldosterone deficiency may also have negative impact on the vascular system (11). Previous reports on cardiovascular and metabolic profiles in CAH adults have mainly included young females, in spite of the fact that males in general have a higher cardiovascular risk, and the results have been contradictory (6,8,9,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). A very recent publication described however a cohort of 203 individuals with CAH including 62 males reporting adverse metabolic profiles (23).…”

Pioglitazone enhances the blood pressure-lowering effect of losartan via synergistic attenuation of angiotensin II-induced vasoconstriction

“…Several experimental studies have shown that pioglitazone has an antihypertensive effect in insulin-resistant and/or hypertensive animal models. [1][2][3][4][5][6][7][8][9][10] Clinical studies have reported that pioglitazone is either neutral [11][12][13] or associated with a mild decrease [14][15][16][17] in blood pressure (BP). The BP-lowering effect of pioglitazone has been described in patients with type 2 diabetes, 14 type 2 diabetics with difficult-to-control hypertension, 15 nondipping diabetic patients, 16 and patients with congenital adrenal hyperplasia.…”

“…The BP-lowering effect of pioglitazone has been described in patients with type 2 diabetes, 14 type 2 diabetics with difficult-to-control hypertension, 15 nondipping diabetic patients, 16 and patients with congenital adrenal hyperplasia. 17 Interestingly, pioglitazone treatment abolishes the increased response of BP to high salt intake in salt-sensitive patients. 12 Our recent experimental findings suggested that consumption of a high-fat, high-sodium (HFS) diet and 20% sucrose solution for 16 consecutive weeks induces a metabolic syndrome (MS) rat model that mimics major characteristics of human MS, such as insulin resistance, dyslipidemia and hypertension.…”

Management Approaches to Congenital Adrenal Hyperplasia in Adolescents and Adults; Latest Therapeutic Developments

“…CAH patients were insulin resistant compared with controls. Treatment with pioglitazone 45 mg improved insulin sensitivity and lowered blood pressure in CAH patients (Kroese et al, 2009). In a study of 203 patients with CAH, 199 of whom had 21-hydroxylase deficiency, in the care of specialized endocrine centers across the United Kingdom National Health Service, it was found that 41% were obese and 29% were insulin resistant (Arit et al, 2010).…”