title: Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents.
abstract: OBJECTIVE
  The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth.
  
  
  METHODS
  We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups.
  
  
  RESULTS
  Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%).
  
  
  CONCLUSIONS
  IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.
authors.affiliation: Yale University School of Medicine, Department of Pediatrics, 330 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Anna M G
authors.initials: AM
authors.lastname: Cali'
authors.forename: Riccardo C
authors.initials: RC
authors.lastname: Bonadonna
authors.forename: Maddalena
authors.initials: M
authors.lastname: Trombetta
authors.forename: Ram
authors.initials: R
authors.lastname: Weiss
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D010641:Phenotype
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin