In this large prospective and outcome-wide investigation of associations between circulating IGF-I and a range of non-cancer outcomes, we found that, after accounting for multiple testing and regression dilution bias, higher IGF-I concentration was positively associated with risk of carpal tunnel syndrome and inversely associated with incident varicose veins, cataracts, diabetes, and iron deficiency anaemia. This evidence concerns the gene IGF1 and diabetes mellitus.