Circulating Receptor Activator of Nuclear factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in Type 2 Diabetes: a prospective, observational cohort study
Abstract Background:Lower limb arterial calcification is a frequent, underestimated but serious diabetic complication. The DIACART study is a prospective cohort study designed to evaluate the determinants of lower limb arterial calcification progression in 198 patients with Type 2 Diabetes.Methods:Lower limb arterial calcification score was determined by computed tomography at baseline and after a mean follow up of 31+/-4 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and glycation markers were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model.Results:At baseline, mean+/-SD and median lower limb arterial calcification scores were, 2364+/- 5613 and 527 respectively and at the end of the study, 3739 +/- 6886 and 1355 respectively. In multivariate analysis, progression of lower limb arterial log calcification score was associated with (β coefficient [slope], 95%CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p < 0.001), triglycerides (0.11, 0.03–0.2, p = 0.007), log(RANKL) (0.07, 0.02–0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15–0.57, p = 0.001) and duration of follow up (0.04, 0.01–0.06, 0.004).Conclusion:In patients with Type 2 Diabetes, lower limb arterial calcification is a frequent and major pathological process which can progress rapidly. Circulating RANKL and triglycerides are independently associated with the progression of lower limb arterial calcification. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.Trial registration: NCT02431234