title: Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function.
abstract: The prevalence of glucose intolerance and type 2 diabetes increases with age. To determine whether the hyperbolic relationship between insulin sensitivity and the insulin response is affected by age and whether the decline in beta-cell function with age is related to increases in intra-abdominal fat or age per se, we studied 220 healthy subjects with fasting glucose <6.1 mmol/l (89 men and 131 women, aged 26-75 years, BMI 18.7-40.4 kg/m(2)). The insulin sensitivity index (S(i)) and the acute insulin response to glucose (AIRg) were determined, and from these beta-cell function was estimated as the disposition index (S(i) x AIRg). Intra-abdominal fat and subcutaneous fat areas were quantified by computed tomography. S(i) (5.40 +/- 0.5 vs. 7.86 +/- 0.7 x10(-5) min(-1)/[pmol/l]), P < 0.01) was decreased and intra-abdominal fat (117 +/- 10 vs. 81 +/- 9 cm(2), P < 0.05) was increased in the oldest (age 60-75 years) versus the youngest (age 26-44 years) quartile. The hyperbolic relationship between S(i) and AIRg was present independent of age; thus, beta-cell function measured as the disposition index (1,412 +/- 120 vs. 2,125 +/- 150 x10(-5) min(-1), P < 0.01) was lower in the oldest versus the youngest quartile. In multiple regression, intra-abdominal fat (r = -0.470, P < 0.001) but not age was associated with S(i), but both intra-abdominal fat (r = -0.198, P = 0.003) and age (r = -0.131, P = 0.05) were correlated with the disposition index. These data suggest that although intra-abdominal fat is a strong determinant of insulin sensitivity and beta-cell function, age has an independent effect on beta-cell function that may contribute to the increased prevalence of type 2 diabetes in older populations.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108, USA. kutzschn@u.washington.edu.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
authors.forename: Darcy B
authors.initials: DB
authors.lastname: Carr
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kodama
authors.forename: Jane B
authors.initials: JB
authors.lastname: Shofer
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Retzlaff
authors.forename: Robert H
authors.initials: RH
authors.lastname: Knopp
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
mesh_terms: D000005:Abdomen; D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin