title: Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study.
abstract: BACKGROUND
  Results of experimental and clinical studies suggest that insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be important determinants of glucose homoeostasis. However, experimental models might also reflect compensatory and adaptive metabolic processes. We therefore prospectively examined the associations between circulating concentrations of IGF-I and IGFBP-1 and development of glucose tolerance.
  
  
  METHODS
  Participants in this cohort study were a random sample of 615 normoglycaemic men and women aged 45-65 years. Participants underwent oral glucose tolerance testing based on WHO definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation between these peptides and subsequent glucose intolerance.
  
  
  RESULTS
  At 4.5 years of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for glucose intolerance, the odds ratio for risk of impaired glucose tolerance or type-2 diabetes for participants with IGF-I concentrations above the median (> or = 152 microg/L) compared with those with concentrations below the median (<152 microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a significant inverse association with subsequent 2-h glucose concentrations, which was independent of correlates of IGF-I and risk factors for glucose tolerance (p for linear trend=0.026). We also found that this inverse association was independently modified by IGFBP-1 (p for interaction=0.011).
  
  
  CONCLUSIONS
  These data show that circulating IGF-I and its interaction with IGFBP-1 could be important determinants of glucose homoeostasis and provide further evidence for the possible protective role of IGF-I against development of glucose intolerance.
authors.affiliation: Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Sandhu
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Heald
authors.forename: J Martin
authors.initials: JM
authors.lastname: Gibson
authors.forename: J Kennedy
authors.initials: JK
authors.lastname: Cruickshank
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000175:diagnosis / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I