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

Cardiovascular Diabetology

Carole-Elodie Aubert¹  Cees Vermeer²  Dominique Bonnefont-Rousselot³  Ziad Massy⁴  David Hajage⁵  Romuald Mentaverri⁶  Nesrine Bouziri⁷  Jean-Michel Davaine⁸  Suzanne Laroche⁹  Chloé Amouyal⁹  Aurélie Carlier⁹  Agnes Hartemann^1,10  Franck Phan^1,10  Olivier Bourron^1,11  Jean-Marc Lacorte^1,12  Christian Funck-Brentano^1,13  Joe-Elie Salem^1,13  Philippe Cluzel^1,14  Alban Redheuil^1,14  Salim Kemel^1,15  Mamadou Hassimiou Diallo^1,16  Stéphane Jaisson^1,17  Philippe Gillery^1,17 

[1] Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Cardiovascular Research Institute CARIM, Maastricht University, Maastricht, The Netherlands;Department of Metabolic Biochemistry, La Pitié Salpêtrière-Charles Foix University Hospital (AP-HP), Paris, France;UTCBS, CNRS UMR8258 – INSERM_1267, Faculty of Pharmacy of Paris, University of Paris, Paris, France;Division of Nephrology, Ambroise Paré Hospital, AP-HP, Université Paris-Saclay, Paris, France;Département de Santé, Centre de Pharmacoépidémiologie (Cephepi), CIC-1421, Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, 75013, Paris, France;INSERM_1088, Centre Universitaire de Recherche en Santé, Université de Picardie Jules Verne, Amiens, France;Sorbonne University, ACTION Study Group, INSERM, UMRS 1166, Institut de Cardiologie, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France;Sorbonne Université, Paris, France;Sorbonne Université, Paris, France;Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Institute of Cardiometabolism and Nutrition ICAN, Paris, France;Sorbonne Université, Paris, France;Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Institute of Cardiometabolism and Nutrition ICAN, Paris, France;INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 06, France;Sorbonne Université, Paris, France;Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Institute of Cardiometabolism and Nutrition ICAN, Paris, France;INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, Paris 06, France;Diabetology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l’Hôpital, Paris, France;Sorbonne Université, Paris, France;Department of Endocrine and Oncologic Biochemistry, AP-HP, Pitié-Salpêtrière Hospital, Paris, France;INSERM U1166, Paris, France;Sorbonne Université, Paris, France;Department of Pharmacology and CIC-1421, AP-HP La Pitié Salpêtrière Charles Foix University Hospital, Paris, France;INSERM, CIC-1901, Paris, France;Institute of Cardiometabolism and Nutrition ICAN, Paris, France;Sorbonne Université, Paris, France;Institute of Cardiometabolism and Nutrition ICAN, Paris, France;Laboratoire d’Imagerie Biomédicale INSERM_1146, CNRS_7371, Paris, France;Assistance Publique-Hôpitaux de Paris (APHP), Department of Radiology, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Sorbonne Université, Paris, France;Laboratoire d’Imagerie Biomédicale INSERM_1146, CNRS_7371, Paris, France;Assistance Publique-Hôpitaux de Paris (APHP), Department of Radiology, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France;Unité de Recherche Clinique Salpêtrière - Charles Foix, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, 75013, Paris, France;University of Reims- Champagne-Ardenne, CNRS, MEDyC UMR 7369, Reims, France;Laboratory of Biochemisry-Pharmacology-Toxicology, University Hospital of Reims, Maison Blanche Hospital, Reims, France;

关键词: Arterial calcification;    Biomarkers;    Calcium score;    Mediacalcosis;    Peripheral artery disease;    Type 2 diabetes;   

DOI  :  10.1186/s12933-020-01122-4

来源: Springer

【 摘 要 】

BackgroundLower 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.MethodsLower 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 markers on calcification progression was analyzed by a multivariate linear regression model.ResultsAt 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 progression 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 < 0.001), triglycerides (0.11, 0.03–0.20, 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), statin use (0.39, 0.06–0.72, p = 0.023) and duration of follow up (0.04, 0.01–0.06, p = 0.004).ConclusionIn patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy.Trial registration NCT02431234

【 授权许可】

CC BY