Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

Anne-Caroline Jeannin (1, 2) , Joe-Elie Salem (1, 3, 4, 2) , Ziad Massy (2) , Carole Elodie Aubert (5) , Cees Vemeer (6) , Chloé Amouyal (1, 2, 4) , Franck Phan (1, 2, 4, 7) , Marine Halbron (1, 2, 4) , Christian Funck-Brentano (1, 3, 4, 2) , Agnès Hartemann (1, 2, 4, 7) , Olivier Bourron (1, 2, 4, 7)

1 SU - Sorbonne Université
2 CHU Pitié-Salpêtrière [AP-HP]
3 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
4 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
5 UNIBE - Universität Bern / University of Bern
6 Maastricht University [Maastricht]
7 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

AIMS/HYPOTHESIS: Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. METHODS: 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA. RESULTS: In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (β = -0.26, p = 0.045) after integrating effects of height (β = -0.38, p = 0.01), insulin treatment (β = 0.42, p = 0.002), retinopathy treated by laser (β = 0.26, p = 0.02), and total cholesterol levels (β = 0.3, p = 0.03) by multivariable analysis. CONCLUSIONS: The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.

Domaines: Biochimie [q-bio.BM]; Endocrinologie et métabolisme; Neurobiologie

Anne-Caroline Jeannin, Joe-Elie Salem, Ziad Massy, Carole Elodie Aubert, Cees Vemeer, et al.. Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes. PLoS ONE, 2020, 15 (2), pp.e0229145. ⟨10.1371/journal.pone.0229145⟩. ⟨inserm-02530894⟩