Below-Knee Arterial Calcification in Type 2 Diabetes: Association With Receptor Activator of Nuclear Factor κB Ligand, Osteoprotegerin, and Neuropathy

Context: Calcification of the arterial wall in diabetes contributes to the arterial occlusive process occurring below the knee. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) system is suspected to be involved in the calcification process. Objective: The aim of the study was to investigate whether there is a link between arterial calcification in type 2 diabetes and 1) conventional cardiovascular risk factors, 2) serum RANKL and OPG levels, and 3) neuropathy. Patients and Methods: We objectively scored, in a cross-sectional study, infrapopliteal vascular calcification using computed tomography scanning in 198 patients with type 2 diabetes, a high cardiovascular risk, and a glomerular filtration rate >30 mL/min. Color duplex ultrasonography was performed to assess peripheral arterial occlusive disease, andmediacalcosis. Peripheral neuropathy was defined by a neuropathy disability score >6. RANKL and OPG were measured in the serum by routine chemistry. Results: Below-knee arterial calcification was associated with arterial occlusive disease. In multivariate logistic regression analysis, the variables significantly and independently associated with the calcification score were age(oddsratio[OR] = 1.08; 95% confidenceinterval [CI] = 1.04-1.13; P < .0001), male gender(OR = 3.53; 95% CI = 1.54-8.08; P = .003), previous cardiovascular disease(OR = 2.78; 95% CI = 1.39-5.59; P = .005), and neuropathy disability score (per 1 point, OR = 1.21; 95% CI = 1.05-1.38; P = .006). The association with ln OPG, significantly associated with calcification score in univariate analysis (OR = 3.14; 95% CI = 1.05-9.40; P = .045), was no longer significant in multivariate analysis. RANKL and OPG/RANKL were not significantly associated with the calcification score. Conclusions: Below-knee arterial calcification severity is clearly correlated with peripheral neuropathy severity and with several usual cardiovascular risk factors, but not with serum RANKL level.