title: Proinsulin and acute insulin response independently predict Type 2 diabetes mellitus in men--report from 27 years of follow-up study.
abstract: OBJECTIVE
  Defects in insulin secretion and insulin action, resulting in compensatory hyperinsulinaemia, are the major abnormalities in the development of Type 2 diabetes mellitus (Type 2 diabetes). The most frequently used conventional immunoreactive assays for insulin cross-react with proinsulin. In short-term studies (<5 years), proinsulin predicts the development of Type 2 diabetes. We studied, with a 27-year follow-up, the longitudinal relationships between intact proinsulin, 32-33 split proinsulin, specific and immunoreactive insulin (IRI), acute insulin response (AIR) after an intravenous glucose load and the development of Type 2 diabetes in a population-based cohort of 50-year-old men.
  
  
  METHODS
  Fasting peptide concentrations were measured in plasma samples, stored since 1970-73 using specific two-site immunometric assays. IRI was measured at baseline using radioimmunoassay. Associations between development of Type 2 diabetes and predictor variables, were analysed with logistic regression. Results are shown as odds ratios (ORs) with their 95% confidence intervals (CIs) for a one standard deviation increase in a predictor variable.
  
  
  RESULTS
  Cumulative incidence of Type 2 diabetes was 33% over 27 years of follow-up. Intact proinsulin (OR, 1.57, CI, 1.16-2.14), and 32-33 split proinsulin (OR, 1.70, CI, 1.20-2.39) were associated with development of Type 2 diabetes, independent of AIR, adjusted for BMI and fasting glucose, whereas specific insulin was not (OR, 1.31, CI, 0.98-1.77), nor was IRI (OR, 1.25, CI, 0.96-1.63). Proinsulin and AIR interacted in the development of Type 2 diabetes (p<0.05).
  
  
  CONCLUSIONS
  Proinsulin predicts the development of Type 2 diabetes mellitus over a 27-year period.
authors.affiliation: Department of Public Health and Caring Sciences/Section of Geriatrics, Uppsala University, Uppsala, Sweden. bjorn.zethelius@pubcare.uu.se
authors.forename: B
authors.initials: B
authors.lastname: Zethelius
authors.forename: L
authors.initials: L
authors.lastname: Byberg
authors.forename: C N
authors.initials: CN
authors.lastname: Hales
authors.forename: H
authors.initials: H
authors.lastname: Lithell
authors.forename: C
authors.initials: C
authors.lastname: Berne
mesh_terms: D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005215:Fasting / Q000097:blood; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009994:Osmolar Concentration; D011379:Prognosis; D011384:Proinsulin / Q000097:blood*; D011498:Protein Precursors / Q000097:blood; D011863:Radioimmunoassay; D013548:Sweden / Q000453:epidemiology
chemical_list: D007328:Insulin; D011498:Protein Precursors; C070703:proinsulin, des(31,32)-; D011384:Proinsulin