title: Below-knee arterial calcification in type 2 diabetes: association with receptor activator of nuclear factor κB ligand, osteoprotegerin, and neuropathy.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Diabetes and Metabolic Diseases (O.B., C.E.A., S.J., A.H.), Radiology (P.C.), Vascular Surgery (F.L.-K., M.D.), Biostatistics and Clinical Research (A.P.), and Cardiology (M.K.) Departments and Laboratory of Biochemistry (F.M.), Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 75013 Paris, France; Sorbonne Universités (O.B., P.C., M.K., A.H.), Université Pierre et Marie Curie University Paris 06, Paris, France; Inserm U1088 (S.L., R.M., M.B., Z.A.M.), Unité de formation et de recherche de Médecine et Pharmacie, Jules Verne Université of Picardy, Amiens, France; Clinical Research Centre Division of Clinical Pharmacology (S.L.), Amiens University Hospital and the Jules Verne University of Picardy, 80000 Amiens, France; Division of Nephrology (Z.A.M.), Ambroise Paré Hospital, 92100 Boulogne-Billancourt, France; Institute of Cardiometabolism and Nutrition (O.B., P.C., M.K., A.H.), 75013 Paris, France; and INSERM UMR_S 1138, Centre de recherche des Cordeliers (O.B., A.H.), 75006 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bourron
authors.forename: Carole Elodie
authors.initials: CE
authors.lastname: Aubert
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Philippe
authors.initials: P
authors.lastname: Cluzel
authors.forename: Frédérique
authors.initials: F
authors.lastname: Lajat-Kiss
authors.forename: Michel
authors.initials: M
authors.lastname: Dadon
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Romuald
authors.initials: R
authors.lastname: Mentaverri
authors.forename: Michel
authors.initials: M
authors.lastname: Brazier
authors.forename: Antoine
authors.initials: A
authors.lastname: Pierucci
authors.forename: Florence
authors.initials: F
authors.lastname: Morel
authors.forename: Sophie
authors.initials: S
authors.lastname: Jacqueminet
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Agnès
authors.initials: A
authors.lastname: Hartemann
mesh_terms: D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology* / Q000473:pathology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D012720:Severity of Illness Index; D061205:Vascular Calcification / Q000097:blood / Q000209:etiology* / Q000473:pathology
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand