Differences in insulin clearance between metabolically healthy and unhealthy obese subjects

Acta Diabetol. 2014 Apr;51(2):257-61. doi: 10.1007/s00592-013-0511-9. Epub 2013 Aug 30.


Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp. MHO subjects exhibited significant lower triglycerides, total cholesterol, 2-h post-challenge glucose, fasting and 2-h post-challenge insulin, steady-state plasma insulin, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase as compared with MAO individuals. Disposition index was higher in MHO subjects as compared with MAO individuals after adjusting for gender and age (P = 0.04). Insulin clearance was significantly lower in MAO individuals as compared with MHO and non-obese individuals. The difference between the two obese subgroups remained significant after adjusting for gender, age, waist circumference, fat mass, and insulin-stimulated glucose disposal (P = 0.03). The hepatic insulin extraction (C-peptide/insulin) in the fasting state was significantly higher in MHO subjects as compared with MAO individuals (P < 0.0001). In univariate analysis adjusted for gender and age, insulin clearance was correlated with hepatic insulin extraction (P = 0.01). In conclusion, insulin clearance differs among obese subjects with different metabolic phenotypes. Impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia observed in MAO individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • C-Peptide / blood
  • Chi-Square Distribution
  • Cholesterol / blood
  • Cross-Sectional Studies
  • Female
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood*
  • Insulin Resistance / physiology*
  • Male
  • Obesity / blood*
  • Triglycerides / blood
  • Waist Circumference / physiology
  • gamma-Glutamyltransferase / blood


  • C-Peptide
  • Insulin
  • Triglycerides
  • Cholesterol
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase