Meta-Analysis and Dose-Response Metaregression: Circulating Insulin-Like Growth Factor I (IGF-I) and Mortality

• Published in: The journal of clinical endocrinology and metabolism 2011-09, Vol.96 (9), p.2912-2920
• Main Authors: Burgers, Anne Marij G, Biermasz, Nienke R, Schoones, Jan W, Pereira, Alberto M, Renehan, Andrew G, Zwahlen, Marcel, Egger, Matthias, Dekkers, Olaf M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cardiovascular Diseases - mortality; Case-Control Studies; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Humans; Insulin-Like Growth Factor I - metabolism; Medical sciences; Neoplasms - mortality; Risk; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-1377

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.