title: Association between metformin use and below-the-knee arterial calcification score in type 2 diabetic patients.
abstract: Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk.
  
  
  
  The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease. Below-the-knee calcification scores were assessed by computed tomography and supplemented by colour duplex ultrasonography. Data on anti-diabetic drugs were carefully collected from the patients' medical records and during patient interviews. Biochemical and clinical data were studied as potential confounding factors.
  
  
  
  Metformin-treated patients had a significantly lower calcification score than metformin-free patients (mean ± standard deviation: 2033 ± 4514 and 4684 ± 9291, respectively; p = 0.01). A univariate analysis showed that metformin was associated with a significantly lower prevalence of severe below-the-knee arterial calcification (p = 0.02). VC was not significantly associated with the use of other antidiabetic drugs, including sulfonylureas, insulin, gliptin, and glucagon like peptide-1 analogues. A multivariate logistic regression analysis indicated that the association between metformin use and calcification score (odds ratio [95% confidence interval] = 0.33 [0.11-0.98]; p = 0.045) was independent of age, gender, tobacco use, renal function, previous cardiovascular disease, diabetes duration, neuropathy, retinopathy, HbA1clevels, and inflammation.
  
  
  
  In patients with type 2 diabetes, metformin use was independently associated with a lower below-the-knee arterial calcification score. This association may contribute to metformin's well-known vascular protective effect. Further prospective investigations of metformin's potential ability to inhibit VC in patients with and without type 2 diabetes are now needed to confirm these results.
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France. aurelien.mary@u-picardie.fr.|Amiens University Medical Center, Pharmacy, 80054, Amiens, France. aurelien.mary@u-picardie.fr.|Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France. aurelien.mary@u-picardie.fr.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Mary
authors.affiliation: Pitié Salpêtrière Hospital, Diabetology, 75005, Paris, France.|Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.|INSERM UMR_S 1138, Centre de recherche des Cordeliers, 75006, Paris, France.|Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hartemann
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.|Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France.|Amiens University Hospital, Clinical Research Centre, Division of Clinical Pharmacology, 80054, Amiens, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.affiliation: INSERM UMR_S 1138, Centre de recherche des Cordeliers, 75006, Paris, France.|Bern University Hospital, University of Bern, General Internal Medicine, 3012, Bern, Switzerland.
authors.forename: Carole Elodie
authors.initials: CE
authors.lastname: Aubert
authors.affiliation: Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.|Pitié Salpêtrière Hospital, Cardiovascular and Interventional Radiology, 75005, Paris, France.|FRANCE2Biomedical Imaging Lab, 75006, Paris, France.
authors.forename: Salim
authors.initials: S
authors.lastname: Kemel
authors.affiliation: Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.|Institute of Cardiometabolism and Nutrition, Paris, France.|Pitié Salpêtrière Hospital, Pharmacology, 75005, Paris, France.|Pitié Salpêtrière Hospital, Clinical Investigation Center, CIC-1421, 75005, Paris, France.
authors.forename: Joe Elie
authors.initials: JE
authors.lastname: Salem
authors.affiliation: Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.|Pitié Salpêtrière Hospital, Cardiovascular and Interventional Radiology, 75005, Paris, France.|FRANCE2Biomedical Imaging Lab, 75006, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cluzel
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.|Amiens University Medical Center, Pharmacy, 80054, Amiens, France.|Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lenglet
authors.affiliation: Ambroise Paré Hospital, Nephrology, 92104, Boulogne-Billancourt, France.|Universite Versailles Saint-Quentin-en-Yvelines, Paris-Ile-de-France-Ouest, 78000, Versailles, France.|INSERM U-1018, Research Centre in Epidemiology and Population Health (CESP) Team 5, 94807, Villejuif, France.
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.|Amiens University Medical Center, Endocrinology and Nutrition, 80054, Amiens, France.|Universite de Picardie Jules Verne, UFR Médecine, 80025, Amiens, France.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lalau
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.|Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France.|Amiens University Hospital, Bone and Endocrine Biology, 80054, Amiens, France.
authors.forename: Romuald
authors.initials: R
authors.lastname: Mentaverri
authors.affiliation: Pitié Salpêtrière Hospital, Diabetology, 75005, Paris, France.|Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.|INSERM UMR_S 1138, Centre de recherche des Cordeliers, 75006, Paris, France.|Institute of Cardiometabolism and Nutrition, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bourron
authors.affiliation: INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France. said.kamel@u-picardie.fr.|Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France. said.kamel@u-picardie.fr.|Amiens University Hospital, Biochemistry, 80054, Amiens, France. said.kamel@u-picardie.fr.
authors.forename: Saïd
authors.initials: S
authors.lastname: Kamel
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D000072226:Computed Tomography Angiography; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007866:Leg / Q000098:blood supply*; D016015:Logistic Models; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D018615:Ultrasonography, Doppler, Color; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Biological statistics; Clinical science; Clinical science and care (all); Human; Imaging (MRI/PET/other); Macrovascular disease; Oral pharmacological agents