Gout as a risk factor for lower-extremity amputation in diabetes: a nationwide, register-based case-control study

Non-healing diabetic foot ulcers are a major precursor to lower-extremity amputation (LEA) in diabetes, and gout may be an overlooked contributor. We hypothesised that individuals with both diabetes and gout have a higher risk of LEA than those with diabetes alone, with the strongest effect at more distal amputation levels.

In a nationwide case-control study of 601,541 individuals with type 2 diabetes, we identified 4912 cases with LEA and 39,101 age- and sex-matched control participants. Gout exposure was determined using ICD-10 diagnoses and Anatomical Therapeutic Chemical codes for urate-lowering therapy. Associations were estimated using conditional logistic regression, adjusting for diabetes duration, peripheral arterial disease, acute myocardial infarction and late diabetes complications.

Gout was associated with an increased risk of LEA (OR 1.85, 95% CI 1.69, 2.02) in unadjusted analyses, and the association remained significant after full adjustment (OR 1.53, 95% CI 1.37, 1.69). A significant trend (p=0.03) was observed across amputation levels, with potentially higher risk at more anatomically distal sites although no statistically significant differences were observed between individual amputation levels: OR 1.37 (95% CI 1.12, 1.68) for above-knee amputations, increasing to OR 1.65 (95% CI 1.32, 2.05) for toe amputations.

Co-existing gout is an independent risk factor for LEA in individuals with type 2 diabetes. The risk is elevated across all amputation levels, with the most pronounced effect potentially being at distal anatomical sites. These findings highlight the need for increased awareness of gout when managing individuals with type 2 diabetes at risk of LEA.