Serum concentration and vascular expression of adiponectin are differentially associated with the diabetic calcifying peripheral arteriopathy

Carole E Aubert, Sophie Liabeuf, Chloé Amouyal, Salim Kemel, Frédérique Lajat-Kiss, Jean-Marc Lacorte, Marine Halbron, Aurélie Carlier, Joe-Elie Salem, Christian Funck-Brentano, Ljubica Perisic Matic, Anna Witasp, Peter Stenvinkel, Franck Phan, Ziad A Massy, Agnès Hartemann, Olivier Bourron, Carole E Aubert, Sophie Liabeuf, Chloé Amouyal, Salim Kemel, Frédérique Lajat-Kiss, Jean-Marc Lacorte, Marine Halbron, Aurélie Carlier, Joe-Elie Salem, Christian Funck-Brentano, Ljubica Perisic Matic, Anna Witasp, Peter Stenvinkel, Franck Phan, Ziad A Massy, Agnès Hartemann, Olivier Bourron

Abstract

Background: Medial calcification in diabetes contributes to the arterial occlusive process occurring below the knee level. Adiponectin is an adipokine with atheroprotective properties and possible protective role against arterial calcification. The aim of the study was to investigate, in type 2 diabetes, the link between vascular expression and serum concentration of adiponectin and (1) peripheral arterial calcification and (2) lower limb occlusive arterial disease.

Methods: Scoring of peripheral vascular calcification and peripheral arterial occlusive disease, using CT-scan and color-duplex ultrasonography respectively, were conducted and explored in relation to serum adiponectin level in a cross sectional study of 197 patients with type 2 diabetes. Vascular adiponectin expression in the arterial wall of diabetic patients with and without medial calcification was evaluated by immunohistochemistry.

Results: Peripheral arterial calcification score was higher in patients with the highest adiponectin concentration. In a multivariate logistic regression analysis, an increase of 1 µg/mL of adiponectin was associated with a 22% increase of arterial calcification (adjusted OR = 1.22; 95% CI 1.03-1.44; p = 0.02). Arterial occlusive score was also higher in patients with adiponectin concentration > median (2.8 ± 4.8 vs 4.2 ± 5.7, p = 0.034). Immunohistochemical analyses showed a strong and specific staining of adiponectin in smooth muscle cells in calcified arteries, with a more pronounced expression of adiponectin in early stages of medial calcification.

Conclusions: Peripheral arterial calcification is positively associated with circulating adiponectin levels in patients with type 2 diabetes, but vascular adiponectin expression is already observed at early stages of calcification. Adiponectin secretion could be a compensatory mechanism against the calcification process.Trial registration DIACART NCT number: NCT02431234. Registered 30 April 2015.

Keywords: Adiponectin; Peripheral arterial disease; Type 2 diabetes; Vascular calcification.

Conflict of interest statement

A patent has been filed on a method using circulating Matrix Gla protein measurement for diagnosis and treating peripheral neuropathies by Assistance Publique Hôpitaux de Paris—APHP). Olivier Bourron, Joe-Elie Salem and Agnès Hartemann are the inventors. The application number is 18306503.6–1118. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Calcification score according to adiponectin levels (*corresponding P = 0.004). Boxplot distribution of participant age for each donning instruction condition with the lower extreme, the lower quartile, median, upper quartile and upper extreme. Lower limb calcification score is expresses in both groups of patients lower or higher to the median of adiponectin levels (3.5 µg/mL). Data are given as mean ± SD for normally distributed measures with addition of (median) for non-normally distributed values for variables with a non-Gaussian distribution or as the number (percentage) for binary variables. NA not applicable, ARB
Fig. 2
Fig. 2
Occlusive score according to adiponectin levels (*corresponding P = 0.034). Boxplot distribution of occlusive score as a function of adiponectin concentration lower or higher than the median of adiponectin concentration in the population. Data are given as the lower extreme, the lower quartile, median, upper quartile and upper extreme
Fig. 3
Fig. 3
Immunohistochemical staining of adiponectin in arteries from patients with type 2 diabetes. Adiponectin (ADIPOQ) protein expression and localization was examined by immunohistochemistry staining in arteries from diabetic patients, classified according to the grade of calcification. ADIPOQ (red signal) was found to be expressed in all stages of calcification, but it was particularly enriched in early stages (grade 1). Smooth muscle cells of the media were specifically immuno positive for ADIPOQ, but the signal was also present in microvessels of the adventitia (particularly grade 2). Images were taken with ×5 magnification and enlarged images with ×15 (size bars included)

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Source: PubMed

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