Reduced Insulin Sensitivity in Adults With Pseudohypoparathyroidism Type 1a

Context: Disruption of theGs beta maternal allele leads to severe obesityandinsulin resistance in miceand early-onset obesity in patients with pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose metabolism have not been systematically characterized in patients with PHP1a. Objective, Design, and Setting: In a cross-sectional, case-control study, we examined insulin sensitivity, beta-cell function, energy expenditure (EE), and sympathetic nervous system activity in adults with PHP1a. Study Participants: PHP1a patients (n = 8) and healthy control subjects (n = 24) matched for age (41 +/- 7 vs 41 +/- 7 years [mean +/- SD]), gender, and percent body fat. Methods: Insulin sensitivity (SI), acute insulin response to glucose, and disposition index were assessed during a frequently sampled iv glucose tolerance test. Oral glucose insulin sensitivity (OGIS) was measured during a mixed meal. EE was measured using whole-room indirect calorimetry. Body composition was assessed via dual-energy x-ray absorptiometry and sympathetic nervous system activity by measuring 24-hour urinary catecholamine concentrations. Results: PHP1a patients were less insulin-sensitive than their matched controls based uon SI and OGIS. Nondiabetic PHP1a patients tended to have a lower SI (P=.09) and reduced OGIS (P =.03). Disposition index, a composite measure of beta-cell function, also tended to be lower in patients (P =.07). Total caloric intake, resting EE, total EE, meal-induced thermogenesis, and 24-hour urinary catecholamine concentrations were not significantly different between the groups. Conclusions: Adults with PHP-1a have reduced insulin sensitivity compared with their matched controls that may contribute to the pathogenesis of glucose intolerance and diabetes in these patients.