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

Abstract

Aims/Hypothesis Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrixgla-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.

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

“…Since dp-ucMGP is a VK-dependent protein, reduced VK status is an independent risk factor for diabetic peripheral neuropathy. Hence, treatment with VK supplements may be a preventive measure in diabetic patients at risk of peripheral neuropathy [142].…”

Beneficial Effects of Vitamin K Status on Glycemic Regulation and Diabetes Mellitus: A Mini-Review

“…Other studies found that the accumulation of advanced glycation end products correlated with coronary artery calcification in patients with type 1 DM (T1DM) [ 43 ] and in those with severe aortic valve stenosis [ 40 ]. Furthermore, high ucMGP levels were detected in DM patients and indicated a risk of arterial calcification, which has been observed in non-diabetic subjects [ 44 , 47 ] and T2DM patients [ 44 , 45 , 46 ].…”

“…Inactive MGP is identified in its carboxylated or phosphorylated forms, including the uncarboxylated MGP (ucMGP), carboxylated but not phosphorylated MGP (dpcMGP), phosphorylated but uncarboxylated (pucMGP), and the fully inactive uncarboxylated, dephosphorylated MGP (dpucMGP) [ 39 , 40 ]. Several studies have described that medial calcification is observed in DM patients, which correlates with the presence of VKDPs [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. An early report indicated that media calcification was higher in DM patients than in the non-diabetic population [ 42 ].…”

“…Moreover, the early differentiation and growth of neurons, dendrite formation, development of mature Schwann cells, and myelination are regulated through the interactions of the extracellular matrix and MGP [ 97 , 98 , 99 ]. Furthermore, dpucMGP plasma levels increased in patients with diabetic peripheral neuropathy and poor VK status, suggesting that MGP plays a role in the homeostasis of the nervous system [ 46 ]. Retinopathy and nephropathy are comorbidities that exist with diabetic neuropathy, and, as other reports have indicated, VK exerts a renoprotective effect, which may extend to the prevention of other diabetes-related complications.…”

“…VK plays a role in the modulation of VKDPs that are involved in vascular cell migration, angiogenesis, and calcification [ 34 ]. Because a VK deficiency results in increased levels of ucMGP, several studies have implicated ucMGP as a risk factor for vascular calcification and CVD [ 38 , 44 , 45 , 46 , 101 , 102 ]. A cohort study found that the plasma level of ucMGP was associated with eGFR in patients with CVD [ 47 ].…”