Primary Prevention of Diabetes Mellitus by Prevention of Obesity in Monkeys

Abstract

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.