| ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity in obese postmenopausal women. | |
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MedLine Citation:
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PMID: 20829805 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The β(2)-adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance. We examined the hypothesis that ADRB2 Arg16Gly-Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women. Obese (>35% body fat), postmenopausal (age 45-75 years) women (n = 123) underwent genotyping, dual-energy X-ray absorptiometry, and computed tomography scans, exercise testing (VO(2(max))), 2-h oral glucose tolerance tests (OGTTs), and hyperinsulinemic-euglycemic clamps (80 mU/m(2)/min). Analysis of covariance (ANCOVA) tested for differences among haplotypes, with race, % body fat, and VO(2(max)) as covariates. We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO(2(max)), insulin sensitivity (M/ΔInsulin), and glucose tolerance (ANOVA, P < 0.05 for all). Women homozygous for Gly16-Gln27 haplotype had the highest % body fat (52.7 ± 1.9%), high abdominal fat, low M/ΔInsulin (0.49 ± 0.08 mg/kg/min/pmol/l/10(2)), and impaired glucose tolerance (IGT) during an OGTT (G(120) = 10.2 ± 0.9 mmol/l). Women homozygous for Gly16-Glu27 haplotype also had low M/ΔInsulin (0.51 ± 0.05 mg/kg/min/pmol/l/10(2)) and IGT (G(120) = 8.2 ± 0.7 mmol/l). Subjects with Arg16-Gln27/Gly16-Gln27 haplotype combination had the highest VO(2(max)) (1.84 ± 0.07 l/min) and M/ΔInsulin (0.7 ± 0.04 mg/kg/min/pmol/l/10(2)), and normal glucose tolerance (G(120) = 6.4 ± 0.4 mmol/l), despite being obese. These data show associations of the ADRB2 Arg16Gly-Gln27Glu haplotype with VO(2(max)) and body composition, and an independent association with glucose metabolism, which persists after controlling for body composition and fitness. This suggests that ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women. |
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Authors:
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Steven J Prior; Andrew P Goldberg; Alice S Ryan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-09-09 |
Journal Detail:
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Title: Obesity (Silver Spring, Md.) Volume: 19 ISSN: 1930-7381 ISO Abbreviation: Obesity (Silver Spring) Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-31 Completed Date: 2011-04-29 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101264860 Medline TA: Obesity (Silver Spring) Country: United States |
Other Details:
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Languages: eng Pagination: 396-401 Citation Subset: IM |
Affiliation:
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Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. sprior@grecc.umaryland.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Blood Glucose / metabolism Body Composition / genetics, physiology Diabetes Mellitus, Type 2 / genetics*, metabolism Female Genotype Glucose Clamp Technique Glucose Tolerance Test Haplotypes Humans Insulin / metabolism Insulin Resistance / genetics* Middle Aged Obesity / genetics*, metabolism Oxygen Consumption* Postmenopause Receptors, Adrenergic, beta-2 / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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P30 DK072488-04S1/DK/NIDDK NIH HHS; P30-AG-12583/AG/NIA NIH HHS; P30-DK-072488/DK/NIDDK NIH HHS; P60 AG012583-10/AG/NIA NIH HHS; P60 DK079637-04/DK/NIDDK NIH HHS; P60-DK-079637/DK/NIDDK NIH HHS; R01 AG019310-05/AG/NIA NIH HHS; R01 AG020116-05/AG/NIA NIH HHS; R01-AG-019310/AG/NIA NIH HHS; R01-AG-020116/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Receptors, Adrenergic, beta-2; 11061-68-0/Insulin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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