title: Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a.
abstract: BACKGROUND
  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
  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.
  
  
  METHODS
  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.
authors.affiliation: MD, 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.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Muniyappa
authors.forename: Mary A
authors.initials: MA
authors.lastname: Warren
authors.forename: Xiongce
authors.initials: X
authors.lastname: Zhao
authors.forename: Sara C
authors.initials: SC
authors.lastname: Aney
authors.forename: Amber B
authors.initials: AB
authors.lastname: Courville
authors.forename: Kong Y
authors.initials: KY
authors.lastname: Chen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brychta
authors.forename: Emily L
authors.initials: EL
authors.lastname: Germain-Lee
authors.forename: Lee S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: Monica C
authors.initials: MC
authors.lastname: Skarulis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010809:Physical Fitness / Q000502:physiology; D011547:Pseudohypoparathyroidism / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin
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