Many, but not all, adult rhesus monkeys spontaneously develop significant increases in body fat mass, and many, but not all, progress to develop overt adult-onset type II diabetes. The purpose of this study was to determine whether both an increase in body fat and onset of diabetes could be simultaneously prevented through long-term maintenance of stable normal adult body weight by caloric titration. Eight adult male monkeys were provided a complete normal chow diet, but with daily amounts restricted and titrated on a weekly basis to maintain a constant body weight (weight-stabilized group). This regimen has been continued for 5–9 yr (mean ± SD of 7 ± 0.5 yr) with monkeys attaining the age of 17.9 ± 0.6 yr and with maintenance of normal body fat (17.7 ± 1.8%). The age-matched ad libitum fed group (18.1 ± 0.2 yr of age) consisted of 19 monkeys maintained under identical laboratory conditions and diet, but with food available ad libitum. Results showed weight-stabilized monkeys weighed significantly < ad libitum fed monkeys (10.4 ± 0.2 vs. 16.1 ± 0.7 kg, respectively, P < 0.05) and had significantly better glucose tolerance as measured by Kglucose (glucose disappearance rate) (3.9 ± 0.3 vs. 2.4 ± 0.2, P ± 0.05). Of the 19 ad libitum fed age-matched monkeys, 4 were overtly diabetic, and 6 others had significantly reduced glucose tolerance. Hyperinsulinemia did not develop in the weight-stabilized group, and β-cell response to glucose remained normal; both were significantly different from the exaggerated levels of the ad libitum fed group (P < 0.05). This form of obesity-associated type II diabetes and impaired glucose tolerance, thus, appears to be completely prevented or onset indefinitely delayed by sustained caloric restriction and maintenance of normal body composition.

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