High osteoprotegerin is associated with development of foot ulcer in type 1 diabetes.
BACKGROUND AND AIM The bone related peptide osteoprotegerin has been linked to vascular calcification and peripheral vascular disease. We investigated the association between osteoprotegerin and development of foot complications in persons with type 1 diabetes. MATERIALS AND METHODS Prospective observational study of 573 persons with type 1 diabetes, 225 women; age [mean+ SD] 42.3+ 10.3years. Plasma osteoprotegerin was measured by ELISA. RESULTS Median (IQR) osteoprotegerin was 2.80(2.35 3.63)mg/L and follow up time (median (range) was 12.7(0.1 15.6)years. Endpoints included: new foot ulceration (n=153) Charcot foot (n=14) vascular surgery/amputation (n=53) loss of foot pulse (n=57) and peripheral neuropathy (n=99) In unadjusted analyses, higher osteoprotegerin was associated with development of all endpoints (p<=0.026) Higher osteoprotegerin remained associated with development of foot ulcer, and the combination of vascular surgery/amputation, loss of foot pulse and neuropathy (p<=0.001) in a sex and age adjusted model. After further adjustment (nephropathy status, smoking, HbA1c, systolic blood pressure, serum cholesterol, high sensitivity C reactive protein, eGFR, and presence of neuropathy and/or claudication and/or foot ulcer at baseline) higher osteoprotegerin remained associated with development of foot ulcer (HR (95% CI) per doubling: 1.75 (1.04 2.97) p=0.037) CONCLUSION Higher osteoprotegerin levels were associated with development of foot ulcer, even after comprehensive adjustment.
Journal of diabetes and its complications