Association between the VKORC1 rs8050894 CC genotype and undercarboxylated osteocalcin levels following vitamin K and D supplementation in Mexican Citizens with T2DM: A randomized clinical trial

Abstract

Type 2 diabetes mellitus (T2DM) involves inadequate insulin production and utilization. Osteocalcin (OC) links bone and energy metabolism, existing as carboxylated (cOC) and undercarboxylated (ucOC) isoforms. The ucOC/cOC ratio is influenced by vitamin K epoxide reductase complex subunit 1 (VKORC1) gene variants and vitamin intake. This study analyzes the effects of vitamin D3 (VD3) and vitamin K2 (VK2) supplementation on ucOC, insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and the percentage of functional pancreatic beta cells (%FPβC) in Mexican Citizens with T2DM carrying the VKORC1 rs8050894 variant. The present randomized clinical trial recruited 40 Mexican subjects with T2DM. Participants were assigned to one of three groups receiving VD3, VK2, or a combination of both over a 3-month period. ucOC levels and insulin were measured using an ELISA assay; glucose and lipid profiles were measured by spectrophotometry (ERBA XL200). HOMA-IR and %FPβC were calculated. The rs8050894 variant was genotyped using allelic discrimination with real-time polymerase chain reaction. All groups exhibited significantly lower levels of glucose and %FPβC. Significant effects were observed in glucose, insulin, %FPβC, and HOMA-IR in CG genotype carriers in the VK2 group. On the other hand, CC genotype carriers showed higher ucOC levels compared to other genotypes in the VK2 and VK2 + D3 intervention groups.

Trial Registration number: NCT04041492. 2019-07-3. https://clinicaltrials.gov/show/NCT04041492