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

Although weight loss in older subjects has been shown to improve insulin sensitivity, it is unclear what effect this lifestyle intervention has on β-cell function. To determine whether diet-induced weight loss can improve β-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 (SI) 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 SI (SI × AIRg and SI × AIRmax), thus providing measures of β-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, SI increased [1.59 ± 0.24 to 2.49 ± 0.32 × 10−4 min−1/(μU/ml) (2.65 ± 0.4 to 4.15 ± 0.5 × 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 β-cell function improved (SI × AIRg, 9.63 ± 2.28 to 12.78 ± 2.58 × 10−3 min−1, P < 0.05; and SI × AIRmax, 51.01 ± 9.2 to 72.69 ± 13.4 × 10−3 min−1, P < 0.05). Thus, the weight loss-associated improvements in both insulin sensitivity and β-cell function may explain the beneficial effects of a lifestyle intervention on delaying the development of diabetes in older subjects.