title: Absence of an acute insulin response predicts onset of type 2 diabetes in a Caucasian population with impaired glucose tolerance.
abstract: BACKGROUND
  In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population.
  
  
  OBJECTIVE
  The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population.
  
  
  METHODS
  The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests.
  
  
  RESULTS
  The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60-12.67] for absence of first insulin peak, 1.58 (95% CI 0.60-4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65-4.88) for lowest vs. highest tertile of the disposition index.
  
  
  CONCLUSIONS
  In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.
authors.affiliation: Department of General Practice, Vrije Universiteit Medical Center, van der Boechorststraat 7, Amsterdam. g.nijpels@vumc.nl
authors.forename: G
authors.initials: G
authors.lastname: Nijpels
authors.forename: W
authors.initials: W
authors.lastname: Boorsma
authors.forename: J M
authors.initials: JM
authors.lastname: Dekker
authors.forename: F
authors.initials: F
authors.lastname: Hoeksema
authors.forename: P J
authors.initials: PJ
authors.lastname: Kostense
authors.forename: L M
authors.initials: LM
authors.lastname: Bouter
authors.forename: R J
authors.initials: RJ
authors.lastname: Heine
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications*; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin