Inactive vitamin K–dependent matrix gla proteins and fetuin-A as potential biomarkers of inflammatory damage in microvascular complication of type2 diabetes

The relationship between vascular calcification mechanisms and mortality in patients with Type 2 Diabetes Mellitus (T2DM) is not fully understood. Macrocirculatory features such as arterial calcifications and stiffness have been associated with circulating dephospho-carboxylated Matrix Gla Protein (dP-ucMGP), which is considered a biomarker of vitamin K status. High plasma dp-ucMGP concentrations indicate low vitamin K status and are associated with vascular calcification. Hyperglycemia is the driving force for the development of diabetic vascular complications and the inflammatory response. Fetuin-A interacts with circulating calcium and phosphorus, increasing their solubility. As a result, calcium deposition in the arteries is reduced. Arterial calcification is the hallmark of vascular disease in T2DM. In this study, it was aimed to investigate serum levels of inactive form dP-ucMGP and its relationship with vitamin K and inflammatory response in patients with microvascular complications of T2DM. A total of 160 T2DM patients were included in this study. These patients were divided into four groups of 40 patients each. These groups were as follows: 40 T2DM patients without microvascular complications (T2DM, n=40), 40 T2DM patients with diabetic nephropathy (DN, n=40), 40 T2DM patients with diabetic retinopathy (DR, n=40), and diabetic neuropathy 40 patients with T2DM (DNR, n=40). Forty healthy individuals were used as the control group. dP-ucMGP, vitamin K, fetuin-A, Tumor Necrosis Factor Alpha (TNF-α) and matrix metalloproteinase (MMP-9) levels were measured by ELISA in all groups. Fetuin-A and TNF-α levels were significantly higher in patients with DNR (P<0,05). MMP-9 levels showed significant changes in patients with T2DM compared to control (𝑃 ≤ 0,05). In addition, when the results were compared with the other patient groups and the control group, there was a significant decrease in DNR (dP-ucMGP) and vitamin K levels (P< 0,05). In this study, a strong negative correlation was found between dp-ucMGP and vitamin K in DNR patients. In conclusion, decreased dp-ucMGP and vitamin K levels in T2DM are associated with microvascular complications and inflammatory response. Therefore, dp-ucMGP may appear as a promising biomarker or therapeutic target in T2DM vascular complications.