title: Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relationship between insulin sensitivity and insulin responses.
abstract: OBJECTIVE
  To determine whether the hyperbolic relationship between insulin sensitivity and the acute insulin response to glucose (AIRg) exists in subjects with impaired fasting glucose (IFG) or decreased glucose tolerance.
  
  
  METHODS
  We studied 219 healthy subjects (88 male and 131 female subjects, aged 26-75 years) with fasting plasma glucose (FPG) <6.11 mmol/l. Subjects underwent an intravenous glucose tolerance test to determine the insulin sensitivity index (Si), AIRg, and the glucose disappearance constant (Kg), the latter a measure of intravenous glucose tolerance.
  
  
  RESULTS
  Si and AIRg were inversely related for the entire cohort, and this relationship was not significantly different from hyperbolic. The inverse relationship between Si and AIRg was not significantly different when compared between groups based on fasting glucose (normal fasting glucose [NFG], FPG <5.56 mmol/l vs. IFG, FPG 5.56-6.11 mmol/l) or by the Kg quartile. However, the curve relating Si and AIRg was left shifted in the IFG compared with NFG group (P < 0.001) and was progressively more left shifted with decreasing Kg (P < 0.001), consistent with decreasing beta-cell function. These changes were not observed for the curves relating Si and fasting insulin, suggesting that in the fasting state beta-cell function is maintained even in patients with mild IFG. Finally, the disposition index (DI) (Si x AIRg) was calculated as a measure of beta-cell function. The DI progressively decreased with increasing FPG, even in the group of subjects classified as NFG.
  
  
  CONCLUSIONS
  The inverse relationship between insulin sensitivity and AIRg is consistent with a hyperbola not only in subjects with normal glucose tolerance but also with mild IFG or decreased Kg. Based on a hyperbolic relationship, a decrease in beta-cell function can be detected as FPG increases, even in patients who are normal glucose tolerant.
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System (151), 1660 S. Columbian Way, Seattle, WA 98108, USA. kutzschn@u.washington.edu
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Utzschneider
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: Darcy B
authors.initials: DB
authors.lastname: Carr
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
authors.forename: Jenny
authors.initials: J
authors.lastname: Tong
authors.forename: Jane B
authors.initials: JB
authors.lastname: Shofer
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Retzlaff
authors.forename: Robert H
authors.initials: RH
authors.lastname: Knopp
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin