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Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a
Ranganath Muniyappa1, Mary A Warren, Xiongce Zhao
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.
The Journal of Clinical Endocrinology and Metabolism
|September 14, 2013
Summary
Adults with pseudohypoparathyroidism (PHP) type 1a exhibit reduced insulin sensitivity compared to healthy individuals. This impaired glucose metabolism may increase the risk of developing diabetes in PHP-1a patients.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Genetics
Background:
- Maternal Gsα allele disruption causes obesity and insulin resistance in mice and early-onset obesity in pseudohypoparathyroidism (PHP) type 1a patients.
- Systematic characterization of insulin resistance and glucose metabolism in PHP type 1a adults is lacking.
Purpose of the Study:
- To investigate insulin sensitivity, beta-cell function, energy expenditure, and sympathetic nervous system activity in adults with PHP type 1a.
- To compare these metabolic parameters between PHP type 1a patients and healthy controls.
Main Methods:
- Cross-sectional, case-control study involving 8 adults with PHP type 1a and 24 healthy controls matched for age, gender, and body fat percentage.
- Assessment of insulin sensitivity (SI, OGIS), acute insulin response to glucose, and disposition index via frequently sampled IV glucose tolerance test and mixed meal test.
- Measurement of energy expenditure (EE) using indirect calorimetry and sympathetic nervous system activity via 24-hour urinary catecholamine concentrations.
Main Results:
- PHP type 1a patients demonstrated significantly reduced insulin sensitivity (SI and OGIS) compared to controls.
- A trend towards a lower disposition index, a measure of beta-cell function, was observed in PHP type 1a patients.
- No significant differences were found in total caloric intake, resting or total EE, meal-induced thermogenesis, or urinary catecholamine concentrations between the groups.
Conclusions:
- Adults with PHP type 1a exhibit impaired insulin sensitivity compared to their matched controls.
- Reduced insulin sensitivity in PHP type 1a may play a role in the development of glucose intolerance and diabetes.
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