title: Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations.
abstract: OBJECTIVE
  Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes mellitus.
  
  
  METHODS
  In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA).
  
  
  RESULTS
  Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared with normal glucose tolerance in both ethnic groups (Europeans F = 6.7, p = 0.002 and Pakistanis F = 4.4, p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently associated with 2-h glucose (beta = 0.16, p = 0.009) and logistic regression indicated a 40% reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49-0.71), p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several established cardiovascular factors, and positively with insulin sensitivity.
  
  
  CONCLUSIONS
  Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention studies and further implicates the insulin-like growth factor system in the development of macrovascular disease.
authors.affiliation: Endocrine Sciences Research Group, Faculty of Medicine and School of Biological Sciences, University of Manchester, Manchester, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Heald
authors.forename: J K
authors.initials: JK
authors.lastname: Cruickshank
authors.forename: L K
authors.initials: LK
authors.lastname: Riste
authors.forename: J E
authors.initials: JE
authors.lastname: Cade
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Greenhalgh
authors.forename: J
authors.initials: J
authors.lastname: Sampayo
authors.forename: W
authors.initials: W
authors.lastname: Taylor
authors.forename: W
authors.initials: W
authors.lastname: Fraser
authors.forename: A
authors.initials: A
authors.lastname: White
authors.forename: J M
authors.initials: JM
authors.lastname: Gibson
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D001824:Body Constitution; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002784:Cholesterol / Q000097:blood; D003971:Diastole; D004739:England; D005006:Ethnicity; D005060:Europe / Q000208:ethnology; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010154:Pakistan / Q000208:ethnology; D012307:Risk Factors; D013599:Systole; D014280:Triglycerides / Q000097:blood; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D002784:Cholesterol