Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality

Burgers, Anne Marij G; Biermasz, Nienke R; Schoones, Jan W; Pereira, Alberto M; Renehan, Andrew G; Zwahlen, Marcel; Egger, Matthias; Dekkers, Olaf M (2011). Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. Journal of clinical endocrinology and metabolism, 96(9), pp. 2912-2920. Chevy Chase, Md.: Endocrine Society 10.1210/jc.2011-1377

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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.

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