Type 2 diabetes critically redefined for nonhuman primates (854.9)

Nonhuman primates (NHPs) naturally develop type 2 diabetes (T2DM) with extraordinary concomitance to T2DM in humans. In order to determine valid criteria for the onset of T2DM in NHPs, a colony of 326 adult NHPs (232 male and 94 female; rhesus monkeys, Macaca mulatta) was studied prospectively, including fasting plasma glucose (FPG), glucose tolerance, HbA1c, insulin, lipid profiles, β‐cell function and insulin sensitivity. A subset of 105 metabolically healthy NHPs was used to establish normal/baseline fasting levels, with normal FPG, 57.3±6.6 mg/dl comparable to ~85 mg/dl in humans and normal HbA1c level, 4.2±0.3 comparable to ~5.5 in humans, thus, 37% and 27% lower than for humans. 112 monkeys developed diabetes while under study and showed the necessity of redefining the onset of T2DM for rhesus, specifically at a fasting glucose of 100 mg/dl or 5.6 mmol/l. Monkeys with a fasting glucose >70 mg/dl were in the progression toward diabetes, and 80‐99 mg/dl was redefined as prediabetes, a level that coincided with sharp changes in β‐cell responses to glucose, and in fasting insulin levels. HbA1c was highly correlated with fasting glucose (r=0.852, p<0.001), with a T2DM diagnostic level of > 5.5% for rhesus. NHPs provide the optimal animal model for studies of the in vivo and molecular pathophysiology of T2DM, and these new diagnostic criteria are essential to improved translation to humans.