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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 5 2019-2025
Copyright © 2003 by The Endocrine Society

Insulin-Like Growth Factor I and Interleukin-6 Contribute Synergistically to Disability and Mortality in Older Women

Anne R. Cappola, Qian-Li Xue, Luigi Ferrucci, Jack M. Guralnik, Stefano Volpato and Linda P. Fried

Department of Medicine, University of Maryland (A.R.C.), Baltimore, Maryland 21201; Departments of Epidemiology (Q.-L.X., L.P.F.) and Medicine (L.P.F.), The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205; Laboratory of Clinical Epidemiology, INRCA Geriatric Department (L.F.), Florence, Italy; Department of Epidemiology, Demography, and Biometry, National Institute on Aging (J.M.G.), Bethesda, Maryland 20892; and Department of Clinical and Experimental Medicine, University of Ferrara (S.V.), Ferrara, Italy

Address all correspondence and requests for reprints to: Anne R. Cappola, M.D., Sc.M., Division of Endocrinology, Diabetes, and Metabolism, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 932 Blockley Hall, Philadelphia, PA 19104-6021. E-mail: acappola{at}cceb.med.upenn.edu.

The physiology of age-related functional decline is poorly understood, but may involve hormones and inflammation. We hypothesized that older women with both low IGF-I and high IL-6 levels are at high risk for disability and death. We assessed walking speed and disability in 718 women enrolled in the Women’s Health and Aging Study I, a 3-yr cohort study with 5-yr mortality follow-up. Women with IGF-I levels in the lowest quartile and IL-6 levels in the highest quartile had significantly greater limitation in walking and disability in mobility tasks and instrumental activities of daily living than those with neither risk factor (adjusted odds ratios, 10.77, 5.14, and 3.66). Women with both risk factors were at greater risk for death (adjusted relative risk, 2.10) as well as incident walking limitation, mobility disability, and disability in activities of daily living compared with those with high IGF-I and low IL-6 levels.

The combination of low IGF-I and high IL-6 levels confers a high risk for progressive disability and death in older women, suggesting an aggregate effect of dysregulation in endocrine and immune systems. The joint effects of IGF-I and IL-6 may be important targets for treatments to prevent or minimize disability associated with aging.

This work was supported by NIA Contract NO1-AG-1-2112 and NIA Grant RO1-AG-19905. Blood collection and processing were supported by grants from Quest Diagnostics, Inc. and Merck \|[amp ]\| Co., Inc.

Abbreviations: ADL, Activities of daily living; BMI, body mass index; CI, 95% confidence interval; IADL, instrumental activities of daily living; OR, odds ratio; RR, relative risk; WHAS I, Women’s Health and Aging Study I.




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