Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a

Ranganath Muniyappa, Mary A. Warren, Xiongce Zhao, Sara C. Aney, Amber B. Courville, Kong Y. Chen, Robert J. Brychta, Emily L. Germain-Lee, Lee S. Weinstein, Monica C. Skarulis

Research output: Contribution to journalArticle

Abstract

Context: Disruption of the Gsα 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, 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.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number11
DOIs
StatePublished - Nov 1 2013

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Pseudohypoparathyroidism
Insulin Resistance
Insulin
Energy Metabolism
Glucose
Sympathetic Nervous System
Catecholamines
Meals
Neurology
Indirect Calorimetry
Glucose Intolerance
Thermogenesis
Glucose Tolerance Test
Body Composition
Energy Intake
Adipose Tissue
Case-Control Studies
Calorimetry
Healthy Volunteers
Medical problems

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Muniyappa, R., Warren, M. A., Zhao, X., Aney, S. C., Courville, A. B., Chen, K. Y., ... Skarulis, M. C. (2013). Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a. Journal of Clinical Endocrinology and Metabolism, 98(11). https://doi.org/10.1210/jc.2013-1594

Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a. / Muniyappa, Ranganath; Warren, Mary A.; Zhao, Xiongce; Aney, Sara C.; Courville, Amber B.; Chen, Kong Y.; Brychta, Robert J.; Germain-Lee, Emily L.; Weinstein, Lee S.; Skarulis, Monica C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 11, 01.11.2013.

Research output: Contribution to journalArticle

Muniyappa, R, Warren, MA, Zhao, X, Aney, SC, Courville, AB, Chen, KY, Brychta, RJ, Germain-Lee, EL, Weinstein, LS & Skarulis, MC 2013, 'Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 11. https://doi.org/10.1210/jc.2013-1594
Muniyappa, Ranganath ; Warren, Mary A. ; Zhao, Xiongce ; Aney, Sara C. ; Courville, Amber B. ; Chen, Kong Y. ; Brychta, Robert J. ; Germain-Lee, Emily L. ; Weinstein, Lee S. ; Skarulis, Monica C. / Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 11.
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abstract = "Context: Disruption of the Gsα 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, 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.",
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AU - Zhao, Xiongce

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AU - Courville, Amber B.

AU - Chen, Kong Y.

AU - Brychta, Robert J.

AU - Germain-Lee, Emily L.

AU - Weinstein, Lee S.

AU - Skarulis, Monica C.

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N2 - Context: Disruption of the Gsα 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, 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.

AB - Context: Disruption of the Gsα 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, 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.

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