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J Clin Endocrinol Metab. 2011 Sep;96(9):2912-20. doi: 10.1210/jc.2011-1377. Epub 2011 Jul 27.

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

Author information

1
Departments of Endocrinology and Metabolism, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Abstract

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.

PMID:
21795450
DOI:
10.1210/jc.2011-1377
[Indexed for MEDLINE]

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