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Cardiovasc Diabetol. 2017 Feb 15;16(1):24. doi: 10.1186/s12933-017-0509-7.

Association between metformin use and below-the-knee arterial calcification score in type 2 diabetic patients.

Mary A1,2,3, Hartemann A4,5,6,7, Liabeuf S8,9,10, Aubert CE6,11, Kemel S5,12,13, Salem JE5,7,14,15, Cluzel P5,12,13, Lenglet A8,16,9, Massy ZA17,18,19, Lalau JD8,20,21, Mentaverri R8,9,22, Bourron O4,5,6,7, Kamel S23,24,25.

Author information

1
INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France. aurelien.mary@u-picardie.fr.
2
Amiens University Medical Center, Pharmacy, 80054, Amiens, France. aurelien.mary@u-picardie.fr.
3
Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France. aurelien.mary@u-picardie.fr.
4
Pitié Salpêtrière Hospital, Diabetology, 75005, Paris, France.
5
Universite Paris-Sorbonne, UMPC - Paris 06, 75005, Paris, Île-de-France, France.
6
INSERM UMR_S 1138, Centre de recherche des Cordeliers, 75006, Paris, France.
7
Institute of Cardiometabolism and Nutrition, Paris, France.
8
INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France.
9
Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France.
10
Amiens University Hospital, Clinical Research Centre, Division of Clinical Pharmacology, 80054, Amiens, France.
11
Bern University Hospital, University of Bern, General Internal Medicine, 3012, Bern, Switzerland.
12
Pitié Salpêtrière Hospital, Cardiovascular and Interventional Radiology, 75005, Paris, France.
13
FRANCE2Biomedical Imaging Lab, 75006, Paris, France.
14
Pitié Salpêtrière Hospital, Pharmacology, 75005, Paris, France.
15
Pitié Salpêtrière Hospital, Clinical Investigation Center, CIC-1421, 75005, Paris, France.
16
Amiens University Medical Center, Pharmacy, 80054, Amiens, France.
17
Ambroise Paré Hospital, Nephrology, 92104, Boulogne-Billancourt, France.
18
Universite Versailles Saint-Quentin-en-Yvelines, Paris-Ile-de-France-Ouest, 78000, Versailles, France.
19
INSERM U-1018, Research Centre in Epidemiology and Population Health (CESP) Team 5, 94807, Villejuif, France.
20
Amiens University Medical Center, Endocrinology and Nutrition, 80054, Amiens, France.
21
Universite de Picardie Jules Verne, UFR Médecine, 80025, Amiens, France.
22
Amiens University Hospital, Bone and Endocrine Biology, 80054, Amiens, France.
23
INSERM U-1088, Pathophysiological Mechanisms and Consequences of Cardiovascular Calcifications, 80025, Amiens, France. said.kamel@u-picardie.fr.
24
Universite de Picardie Jules Verne, UFR Pharmacie, 80025, Amiens, France. said.kamel@u-picardie.fr.
25
Amiens University Hospital, Biochemistry, 80054, Amiens, France. said.kamel@u-picardie.fr.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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, HbA1c levels, and inflammation.

CONCLUSIONS:

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.

KEYWORDS:

Biological statistics; Clinical science; Clinical science and care (all); Human; Imaging (MRI/PET/other); Macrovascular disease; Oral pharmacological agents

PMID:
28202017
PMCID:
PMC5311847
DOI:
10.1186/s12933-017-0509-7
[Indexed for MEDLINE]
Free PMC Article

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