title: Differences in insulin clearance between metabolically healthy and unhealthy obese subjects.
abstract: 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.
authors.affiliation: Department of Systems Medicine, University of Rome-Tor Vergata, Rome, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marini
authors.forename: Simona
authors.initials: S
authors.lastname: Frontoni
authors.forename: Elena
authors.initials: E
authors.lastname: Succurro
authors.forename: Franco
authors.initials: F
authors.lastname: Arturi
authors.forename: Teresa V
authors.initials: TV
authors.lastname: Fiorentino
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002096:C-Peptide / Q000097:blood; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000097:blood*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000502:physiology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D002096:C-Peptide; D007328:Insulin; D014280:Triglycerides; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase