Longitudinal Dynamics of Body Weight Change in the Development of Type 2 Diabetes

Objective: The aim of this study was to test the obesity-type 2 diabetes mellitus (T2DM) link in the context of longitudinal changes in body weight during the progression to diabetes in mature adult nonhuman primates (NHP). Design and Methods: A colony of 245 adult rhesus monkeys aged 8-41 years with 179 males were used to define overweight in males as a body weight: >= 13.5 kg or body fat (BF) >= 18% and obesity as >= 16.5 kg or BF >= 27%, and overweight in nonpregnant females was identified as a body weight >8.5 kg or BF >21% and obesity as >= 10.5 kg or BF >= 30%. A subgroup of 48 males (24 T2DM and 24 age-matched non-T2DM) males were studied before and following the onset of overt T2DM for the effects of changes in body weight and obesity in inducing this conversion to overt T2DM. Results: Three years before overt T2DM, mean body weight was 18.4 +/- 3.3 kg. The DM-destined group body weight was 3.2 +/- 1.1 kg greater and had a longer duration and greater severity of obesity, with peak body weight reached at 3.2 +/- 1.8 years before overt T2DM. At DM onset the two groups did not differ significantly in body weight or adiposity. Conclusions: The natural progression from pre-DM to overt T2DM is caused neither by the amount of excess body weight at DM onset nor by the proximate increases in body weight/adiposity during the pre-DM period of impaired glucose tolerance. Obesity was, however, essential preceding all NHP cases that developed T2DM.