Abstract
We aimed to investigate associations between diabetes mellitus and incident fracture, stratified by diabetes type (1 or 2), disease duration and microvascular complications of diabetes. This prospective cohort analysis used data from the UK Biobank, a large population-based cohort of participants recruited 2006-2010 at age 40-69 yr. The exposure was type 1 or type 2 diabetes at baseline, with the outcome of first incident osteoporotic fracture. Poisson regression was used to calculate incidence rate ratios (IRRs) for osteoporotic fracture to investigate prospective relationships between diabetes type 1 or 2 and fracture risk independent of traditional clinical risk factors, estimated BMD by heel ultrasound (eBMD), adiposity, and C-reactive protein (CRP). The role of diabetic microvascular complications and associations between diabetes duration and fracture risk were studied. There were 498 949 participants (271 882 women, mean age 56 yr; 227 067 men, 57 yr). In fully adjusted models, type 1 and 2 diabetes were associated with increased fracture risk [type 1; IRR: 2.93 (95% CI: 2.37, 3.62); type 2: 1.25 (1.14, 1.38)], similar by sex. The magnitude of risk associated with type 2 diabetes increased with the duration of disease. Increasing number of microvascular complications was associated with greater fracture risk [any vs no complications, IRR 2.03 (1.57, 2.62)]. Diabetes is associated with increased risk of fracture (magnitude of effect greater in type 1 than type 2 diabetes). Associations were partly independent of traditional risk factors, adiposity, eBMD, and CRP. Type 2 diabetes disease duration and the presence of microvascular complications in both types were dose-dependent risk factors for fracture.