title: Insulin resistance, impaired early insulin response, and insulin propeptides as predictors of the development of type 2 diabetes: a population-based, 7-year follow-up study in 70-year-old men.
abstract: OBJECTIVE
  Defects in insulin secretion and insulin action are the major abnormalities in the development of type 2 diabetes. In middle-aged subjects, elevated plasma proinsulin has been found to predict type 2 diabetes. Therefore, our aim was to study the longitudinal relationships between baseline determinations of insulin sensitivity index (S(i)) assessed by euglycemic insulin clamp, the early insulin response (EIR) at an oral glucose tolerance test (OGTT), fasting intact proinsulin, 32-33 split proinsulin and specific insulin, and the development of type 2 diabetes in a population-based cohort of 70-year-old nondiabetic men (n = 667) with 7-year follow-up.
  
  
  METHODS
  A euglycemic insulin clamp study and a 75-g OGTT were performed at baseline, and fasting peptide concentrations were measured using specific two-site immunometric assays. Results from logistic regression models are presented as odds ratios (ORs) with 95% CIs for a 1-SD increase in the predictor variable.
  
  
  RESULTS
  In separate multivariate analyses adjusted for EIR (OR 0.72, 95% CI 0.59-0.89) and S(i) (0.68, 0.58-0.88), 32-33 split proinsulin (1.49, 1.18-1.88) or intact proinsulin (1.30, 1.04-1.63) were significantly associated with the development of type 2 diabetes, whereas specific insulin (1.24, 0.91-1.66) was not. The significant associations between 32-33 split or intact proinsulin and the development of type 2 diabetes were unaltered after adjustment for BMI and glucose tolerance.
  
  
  CONCLUSIONS
  Insulin propeptides predicted type 2 diabetes over a 7-year period in elderly men, independent of the EIR and S(i).
authors.affiliation: Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Box 609, SE-75125 Uppsala, Sweden. bjorn.zethelius@pubcare.uu.se
authors.forename: Björn
authors.initials: B
authors.lastname: Zethelius
authors.forename: C Nicholas
authors.initials: CN
authors.lastname: Hales
authors.forename: Hans O
authors.initials: HO
authors.lastname: Lithell
authors.forename: Christian
authors.initials: C
authors.lastname: Berne
mesh_terms: D000368:Aged; D000886:Anthropometry; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D049628:Body Size; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008954:Models, Biological; D011384:Proinsulin / Q000097:blood*; D013548:Sweden / Q000453:epidemiology; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin