title: Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality.
abstract: BACKGROUND
  IGF-I plays a central role in metabolism and growth regulation. High IGF-I levels are associated with increased cancer risk and low IGF-I levels with increased risk for cardiovascular disease.
  
  
  OBJECTIVE
  Our objective was to determine the relationship between circulating IGF-I levels and mortality in the general population using random-effects meta-analysis and dose-response metaregression.
  
  
  METHODS
  We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies.
  
  
  METHODS
  Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility.
  
  
  METHODS
  Data extraction was performed by two investigators independently, using a standardized data extraction sheet.
  
  
  RESULTS
  Twelve studies, with 14,906 participants, were included. Overall, risk of bias was limited. Mortality in subjects with low or high IGF-I levels was compared with mid-centile reference categories. All-cause mortality was increased in subjects with low as well as high IGF-I, with a hazard ratio (HR) of 1.27 (95% CI = 1.08-1.49) and HR of 1.18 (95% CI = 1.04-1.34), respectively. Dose-response metaregression showed a U-shaped relation of IGF-I and all-cause mortality (P = 0.003). The predicted HR for the increase in mortality comparing the 10th IGF-I with the 50th percentile was 1.56 (95% CI = 1.31-1.86); the predicted HR comparing the 90th with the 50th percentile was 1.29 (95% CI = 1.06-1.58). A U-shaped relationship was present for both cancer mortality and cardiovascular mortality.
  
  
  CONCLUSIONS
  Both low and high IGF-I concentrations are associated with increased mortality in the general population.
authors.affiliation: Departments of Endocrinology and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Anne Marij G
authors.initials: AM
authors.lastname: Burgers
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Jan W
authors.initials: JW
authors.lastname: Schoones
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Renehan
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
mesh_terms: D002318:Cardiovascular Diseases / Q000401:mortality*; D016022:Case-Control Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009369:Neoplasms / Q000401:mortality*; D012306:Risk
chemical_list: D007334:Insulin-Like Growth Factor I