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J Clin Endocrinol Metab. 2013 Nov;98(11):E1796-801. doi: 10.1210/jc.2013-1594. Epub 2013 Sep 12.

Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a.

Author information

  • 1MD, Chief, Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive MSC 1613, Building 10, CRC, Room 6-3940, Bethesda, Maryland 20892-1613. monicas@intra.niddk.nih.gov.

Abstract

CONTEXT:

Disruption of the Gsα maternal allele leads to severe obesity and insulin resistance in mice and 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, β-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 upon 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 β-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.

PMID:
24030943
[PubMed - indexed for MEDLINE]
PMCID:
PMC3816268
Free PMC Article
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