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

Jeannin, Anne-Caroline; Salem, Joe-Elie; Massy, Ziad; Aubert, Carole Elodie; Vemeer, Cees; Amouyal, Chloé; Phan, Franck; Halbron, Marine; Funck-Brentano, Christian; Hartemann, Agnès; Bourron, Olivier (2020). Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes. PLoS ONE, 15(2), e0229145. Public Library of Science 10.1371/journal.pone.0229145

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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.

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