Heterogeneity of insulin responses: phases leading to type 2 (non-insulin-dependent) diabetes mellitus in the rhesus monkey

Diabetologia. 1986 Oct;29(10):713-9. doi: 10.1007/BF00870281.


To determine the natural history of the development of Type 2 (non-insulin-dependent) diabetes mellitus, basal plasma insulin and glucose levels and responses to intravenous glucose tolerance tests were determined over a period of 6 years in 42 adult male rhesus monkeys (Macaca mulatta). Among the 28 obese monkeys (percent body fat greater than 22%) over the age of 10 years, 9 developed overt Type 2 diabetes (fasting plasma glucose, greater than 7.8 mmol/l, and reduced glucose disappearance rates, KG less than 1.5), and 14 monkeys have shown progressive changes which suggest that they may also become diabetic. Application of a highly constant antecedent diet and a consistent 16-h fast minimized experimental variability, and permitted the identification of 8 phases in the progression from normal lean young adult to overt Type 2 diabetes. The earliest changes which could be detected were a slight increase followed by a progressive rise in fasting plasma insulin levels and an increased insulin secretion in response to a glucose stimulus. These events preceded by several years the onset of a gradual deterioration of glucose tolerance. We found that hyper-, normo-, or hypoinsulinaemia could be associated with normoglycaemia or varying degrees of hyperglycaemia; however, the prospective longitudinal study of individual monkeys clearly identified this apparent heterogeneity of plasma insulin and glucose levels as reflecting sequential changes in a continuum of events preceding or accompanying the development of impaired glucose tolerance and Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Body Weight
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diet
  • Fasting
  • Insulin / blood*
  • Macaca mulatta
  • Male


  • Blood Glucose
  • Insulin