CONTEXT: 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. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies. STUDY SELECTION: Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility. DATA EXTRACTION: Data extraction was performed by two investigators independently, using a standardized data extraction sheet. DATA SYNTHESIS: 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.
CONTEXT: 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. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, and Cochrane Library from 1985 to September 2010 to identify relevant studies. STUDY SELECTION: Population-based cohort studies and (nested) case-control studies reporting on the relation between circulating IGF-I and mortality were assessed for eligibility. DATA EXTRACTION: Data extraction was performed by two investigators independently, using a standardized data extraction sheet. DATA SYNTHESIS: 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: Andrea Giustina; Philippe Chanson; David Kleinberg; Marcello D Bronstein; David R Clemmons; Anne Klibanski; Aart J van der Lely; Christian J Strasburger; Steven W Lamberts; Ken K Y Ho; Felipe F Casanueva; Shlomo Melmed Journal: Nat Rev Endocrinol Date: 2014-02-25 Impact factor: 43.330
Authors: Tharini Sivasubramaniyam; Stephanie A Schroer; Angela Li; Cynthia T Luk; Sally Yu Shi; Rickvinder Besla; David W Dodington; Adam H Metherel; Alex P Kitson; Jara J Brunt; Joshua Lopes; Kay-Uwe Wagner; Richard P Bazinet; Michelle P Bendeck; Clinton S Robbins; Minna Woo Journal: JCI Insight Date: 2017-07-20
Authors: Marcello Maggio; Chiara Cattabiani; Fulvio Lauretani; Stefania Bandinelli; Francesca De Vita; Elisabetta Dall'Aglio; Andrea Corsonello; Fabrizia Lattanzio; Giuseppe Paolisso; Luigi Ferrucci; Gian Paolo Ceda Journal: J Gerontol A Biol Sci Med Sci Date: 2013-05-13 Impact factor: 6.053
Authors: Robert C Kaplan; Garrett Strizich; Chino Aneke-Nash; Clara Dominguez-Islas; Petra Bužková; Howard Strickler; Thomas Rohan; Michael Pollak; Lewis Kuller; Jorge R Kizer; Anne Cappola; Christopher I Li; Bruce M Psaty; Anne Newman Journal: J Clin Endocrinol Metab Date: 2017-01-01 Impact factor: 5.958
Authors: Daniel Carlzon; Johan Svensson; Max Petzold; Magnus K Karlsson; Östen Ljunggren; Åsa Tivesten; Dan Mellström; Claes Ohlsson Journal: J Clin Endocrinol Metab Date: 2014-07-24 Impact factor: 5.958