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

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.
Competing Interests: 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. Status of application: recorded. The patent specific aspect of manuscript covered in patent application: use of circulating Matrix Gla protein measurement for diagnosis and treating peripheral neuropathies. This study was supported by a fund from Lilly Company. The company was involved neither in the design of the study nor in data collection. This does not alter our adherence to PLOS ONE policies on sharing data and materials.