Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower li
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ORIGINAL INVESTIGATION
Cardiovascular Diabetology Open Access
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 Olivier Bourron1,2,6,18,21* , Franck Phan1,2,6,18, Mamadou Hassimiou Diallo3, David Hajage19, Carole‑Elodie Aubert2, Aurélie Carlier1,2,6, Joe‑Elie Salem1,4,5,6, Christian Funck‑Brentano1,4,5,6, Salim Kemel1,7,8, Philippe Cluzel1,6,7,8, Alban Redheuil1,6,7,8, Jean‑Michel Davaine1, Ziad Massy9, Romuald Mentaverri10, Dominique Bonnefont‑Rousselot11,12, Philippe Gillery13,14, Stéphane Jaisson13,14, Cees Vermeer15, Jean‑Marc Lacorte1,16,17, Nesrine Bouziri20, Suzanne Laroche1,2,6, Chloé Amouyal1,2,6 and Agnes Hartemann1,2,6,18
Abstract Background: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. Methods: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these mark‑ ers 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. Using multivariate analysis, the pro‑ gression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00–1.04, p 50 years
for men and > 60 years for women. Exclusion criteria were: [1] an estimated glomerular filtration rate (GFR) calculated by the modification of diet in renal disease equation 3.9 mmol/l using a Konelab kit. Inter- and intra-assay coefficients of variation were 2.2% and 0.9%, 1.3% and 0.9%, 3.5% and 0.97%, 1.3%
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and 0.9%, respectively for total cholesterol, HDL-cholesterol, triglycerides and LDL-cholesterol, respectively. Serum human Fetuin A was evaluated using ELISA kit (TECOmedical Group, France) and was performed according to instructions provided by Epitope Diagnostics (intra-assay coefficient of variation:
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