Impact of obesity on insulin action in volunteers with normal glucose tolerance: demonstration of a threshold for the adverse effect of obesity

J Clin Endocrinol Metab. 1990 Apr;70(4):1114-8. doi: 10.1210/jcem-70-4-1114.


We examined whether obesity must first exceed a critical threshold before it begins to impair insulin action in volunteers with normal glucose tolerance. Forty-nine healthy volunteers, whose ideal body weight ranged from 80-240%, underwent euglycemic clamps during sequential insulin infusions of 0.4, 1.0, and 10 mU/kg.min. Insulin sensitivity was assessed by estimation of the plasma insulin concentration that produced half-maximal glucose disposal (EC50). Glucose disposal during the highest insulin infusion was used as an index of maximal insulin responsiveness. There was a significant correlation between body mass index and insulin sensitivity (EC50) best fitted by a straight line that broke at a body mass index of 26.8 kg/m2 (P less than 0.05). Below this breakpoint (26.8 kg/m2), there was no significant correlation (r = 0.1), whereas above the breakpoint there was a strong positive correlation (r = 0.8; P less than 0.001) between EC50 and body mass index. In contrast, insulin responsiveness was not significantly correlated with body mass index (r = 0.1). We conclude that insulin sensitivity for glucose disposal is impaired in human subjects with normal glucose tolerance who exceed a critical threshold of obesity, which corresponds to an ideal body weight of 120%. This threshold is consistent with the nonlinear (J-shaped) relationship between obesity and its other adverse health consequences, and may have important implications for desirable weight goals.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Body Mass Index
  • Body Weight
  • Dose-Response Relationship, Drug
  • Female
  • Glucose / pharmacokinetics*
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Insulin / administration & dosage*
  • Insulin / blood
  • Insulin / pharmacology
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / metabolism*


  • Blood Glucose
  • Insulin
  • Glucose