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Do Height-Related Variations in Insulin-Like Growth Factors Underlie the Associations of Stature with Adult Chronic Disease?

Department of Social Medicine (D.G., J.L.D.), University of Bristol, Bristol BS8 2PR; Department of Health Sciences (S.E.O.), University of York and Hull York Medical School, York YO10 5DD; Division of Primary Health Care (T.J.P.), University of Bristol, Bristol BS6 6JL; Division of Surgery (D.G., R.P., J.M.P.H.), University of Bristol, Bristol BS2 8HW; Academic Urology Unit (F.C.H.), University of Sheffield, Sheffield S10 2JF; and Oncology Centre (D.E.N.), Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom

Address all correspondence and requests for reprints to: David Gunnell, Senior Lecturer in Epidemiology and Public Health Medicine, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, United Kingdom. E-mail: D.J.Gunnell{at}bristol.ac.uk.

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50–70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (P_trend = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (P_trend < 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

This work was supported by National Health Service (NHS) South and West Research and Development. The ProtecT study is funded by the NHS Health Technology Assessment Program.

Abbreviations: BMI, Body mass index; IGFBP, IGF binding protein.

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