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Low Circulating Insulin-Like Growth Factor I Bioactivity in Elderly Men Is Associated with Increased Mortality

Division of Endocrinology (M.P.B., A.W.v.d.B., L.J.H., K.v.d.W., P.M.v.K., S.W.J.L., J.A.M.J.L.J.), Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; and Medical Research Laboratories (J.F.), Clinical Institute and Medical Department M, Aarhus University Hospital, Aarhus C, DK-8000 Denmark

Address all correspondence and requests for reprints to: Michael Pascal Brugts, Department of Internal Medicine, Erasmus Medical Center, Room Ee569, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: m.brugts{at}erasmusmc.nl.

Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGF-I.

Objective: Our objective was to study IGF-I bioactivity in relation to human survival.

Design, Setting, and Study Participants: We conducted a prospective observational study at a clinical research center at a university hospital of 376 healthy elderly men (aged 73–94 yr).

Main Outcome Measures: IGF-I bioactivity was determined by the IGF-I kinase receptor activation assay. Total and free IGF-I were determined by IGF-I immunoassays. Mortality was registered during follow-up (mean 82 months).

Results: During the follow-up period of 8.6 yr, 170 men (45%) died. Survival of subjects in the highest quartile of IGF-I bioactivity was significantly better than in the lowest quartile, both in the total study group [hazard ratio (HR) = 1.8; 95% confidence interval (95% CI) = 1.2–2.8; P = 0.01] as well as in subgroups having a medical history of cardiovascular disease (HR = 2.4; 95% CI = 1.3–4.3; P = 0.003) or a high inflammatory risk profile (HR = 2.3; 95% CI = 1.2–4.5; P = 0.01). Significant relationships were not observed for total or free IGF-I.

Conclusion: Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk.