Circulating insulin-like growth factor-I and risk of 25 common conditions: outcome-wide analyses in the UK Biobank Study

Background While there is strong epidemiological evidence that circulating insulin-like growth factor-I (IGF-I) is associated with a higher risk of several cancers, little is known about its association with non-cancer outcomes. We investigated associations of circulating IGF-I with risk of 25 common conditions, other than cancer, in a large British cohort. Methods Study participants were 318 749 middle-aged adults enrolled in the UK Biobank Study. Serum IGF-I concentration was measured in samples collected at baseline (2006-2010), and re-measured in 12 334 participants after an average of 4.3 years. We followed-up participants over an average of 11.5 years by linking to hospital admissions and mortality registries. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between circulating IGF-I and 25 common conditions, using the repeated IGF-I measurements to correct for regression dilution bias. Results After correction for multiple testing ( P <0.002), IGF-I was positively associated with carpal tunnel syndrome (HR per 5 nmol/l higher concentration=1.12, 95% CI, 1.08-1.16), and inversely associated with varicose veins (0.90, 0.85-0.95), cataracts (0.97, 0.95-0.99), diabetes (0.92, 0.90-0.95), and iron deficiency anaemia (0.90, 0.86-0.93). The associations for cataracts and diabetes attenuated when restricted to cases diagnosed after five or more years of follow-up, suggesting that these associations were likely affected by reverse causality. Conclusions Higher IGF-I concentration might be associated with the risk for several conditions, but genetic studies are needed to clarify which associations may be causal. Key messages Evidence on the association between circulating insulin-like growth factor-I (IGF-I) and risk of many common, non-cancer health outcomes in the general population is relatively limited. This study used an outcome-wide approach to prospectively examine associations of circulating IGF-I with risk of 25 common conditions in a large, prospective cohort of over 300,000 UK adults. Our study showed that circulating IGF-I is associated with risks of several common diseases and conditions; IGF-I was positively associated with carpal tunnel syndrome and inversely associated with varicose veins, cataracts, diabetes, and iron deficiency anaemia. Further research is needed to evaluate whether these differences in risk may reflect causal relationships.