RESUMEN
BACKGROUND: Medial calcification in diabetes contributes to the arterial occlusive process occurring below the knee level. Adiponectin is an adipokine with atheroprotective properties and possible protective role against arterial calcification. The aim of the study was to investigate, in type 2 diabetes, the link between vascular expression and serum concentration of adiponectin and (1) peripheral arterial calcification and (2) lower limb occlusive arterial disease. METHODS: Scoring of peripheral vascular calcification and peripheral arterial occlusive disease, using CT-scan and color-duplex ultrasonography respectively, were conducted and explored in relation to serum adiponectin level in a cross sectional study of 197 patients with type 2 diabetes. Vascular adiponectin expression in the arterial wall of diabetic patients with and without medial calcification was evaluated by immunohistochemistry. RESULTS: Peripheral arterial calcification score was higher in patients with the highest adiponectin concentration. In a multivariate logistic regression analysis, an increase of 1 µg/mL of adiponectin was associated with a 22% increase of arterial calcification (adjusted OR = 1.22; 95% CI 1.03-1.44; p = 0.02). Arterial occlusive score was also higher in patients with adiponectin concentration > median (2.8 ± 4.8 vs 4.2 ± 5.7, p = 0.034). Immunohistochemical analyses showed a strong and specific staining of adiponectin in smooth muscle cells in calcified arteries, with a more pronounced expression of adiponectin in early stages of medial calcification. CONCLUSIONS: Peripheral arterial calcification is positively associated with circulating adiponectin levels in patients with type 2 diabetes, but vascular adiponectin expression is already observed at early stages of calcification. Adiponectin secretion could be a compensatory mechanism against the calcification process.Trial registration DIACART NCT number: NCT02431234. Registered 30 April 2015.
RESUMEN
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 κB 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, and mediacalcosis. 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 (odds ratio [OR] = 1.08; 95% confidence interval [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.