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Diet-Induced Weight Loss Is Associated with an Improvement in ß-Cell Function in Older Men

Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine (K.M.U., S.E.K.), Veterans Affairs Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington 98108; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Department of Medicine (D.B.C.), University of Washington, Seattle, Washington; and Medicine/Gerontology and Geriatric Medicine, Department of Medicine (S.M.B., R.S.S.), Harborview Medical Center and University of Washington, Seattle, Washington

Address all correspondence and requests for reprints to: Kristina M. Utzschneider, M.D., Veterans Affairs Puget Sound Health Care System (151), 1660 South Columbian Way, Seattle, Washington 98108. E-mail: kutzschn{at}u.washington.edu.

Although weight loss in older subjects has been shown to improve insulin sensitivity, it is unclear what effect this lifestyle intervention has on ß-cell function. To determine whether diet-induced weight loss can improve ß-cell function in older subjects, we studied 19 healthy male subjects (age, 65.4 ± 0.9 yr; body mass index, 30.9 ± 0.6 kg/m²; mean ± SEM) before and after a 3-month 1200-kcal/d diet. The insulin sensitivity index (S_I) was quantified using Bergman’s minimal model. The acute insulin response to glucose (AIRg) and the maximal glucose-potentiated insulin response (AIRmax) were determined and then adjusted for S_I (S_I x AIRg and S_I x AIRmax), thus providing measures of ß-cell function. Subjects demonstrated significant weight loss (95.6 ± 2.4 to 86.1 ± 2.5 kg; P < 0.001). Both fasting plasma glucose [97.3 ± 1.6 to 95.1 ± 1.3 mg/dl (5.4 ± 0.09 to 5.3 ± 0.07 mM); P = 0.05] and insulin [18.5 ± 1.3 to 12.2 ± 1.0 µU/ml (110.9 ± 7.7 to 73.5 ± 5.9 pM); P < 0.001] levels decreased. With weight loss, S_I increased [1.59 ± 0.24 to 2.49 ± 0.32 x 10^–4 min^–1/(µU/ml) (2.65 ± 0.4 to 4.15 ± 0.5 x 10^–5 min^–1/pM); P < 0.001], whereas both AIRg [63.4 ± 13.4 to 51.0 ± 10.7 µU/ml (380 ± 80 to 306 ± 64 pM); P < 0.05] and AIRmax [314 ± 31.4 to 259.9 ± 33.4 µU/ml (1886 ± 188 to 1560 ± 200 pM); P < 0.05] decreased. Overall ß-cell function improved (S_I x AIRg, 9.63 ± 2.28 to 12.78 ± 2.58 x 10^–3 min^–1, P < 0.05; and S_I x AIRmax, 51.01 ± 9.2 to 72.69 ± 13.4 x 10^–3 min^–1, P < 0.05). Thus, the weight loss-associated improvements in both insulin sensitivity and ß-cell function may explain the beneficial effects of a lifestyle intervention on delaying the development of diabetes in older subjects.

This work was supported by the Medical Research Service of the Department of Veteran Affairs and National Institutes of Health Grants AG-08673, DK-02654, DK-17047, T32 HL-07028, and RR-37.

Abbreviations: AIR, Acute insulin response; AIRarg, AIR to arginine; AIRg, AIR to iv glucose; AIRmax, maximal glucose-potentiated insulin response; BMI, body mass index; DI, disposition index; DPP, Diabetes Prevention Program; FSIGT, frequently sampled iv glucose tolerance; GCRC, General Clinical Research Center; IAF, intraabdominal fat; IGT, impaired glucose tolerance; K_g, glucose disappearance constant; PG50, glucose level at 50% AIRmax; S_I, insulin sensitivity index; SQAF, sc abdominal fat.

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Weight Loss Linked To Better Beta-Cell Function

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