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Impact of Intra-Abdominal Fat and Age on Insulin Sensitivity and ß-Cell Function

¹ Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, Harborview Medical Center and the University of Washington, Seattle, Washington
² Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
³ Department of Rehabilitation and Research and Development, Veterans Affairs Puget Sound Health Care System, Seattle, Washington

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 ß-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/m²). The insulin sensitivity index (S_i) and the acute insulin response to glucose (AIRg) were determined, and from these ß-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 cm², 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, ß-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 ß-cell function, age has an independent effect on ß-cell function that may contribute to the increased prevalence of type 2 diabetes in older populations.

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