The associations between functional vitamin K status and all-cause mortality, cardiovascular disease and end-stage kidney disease in persons with type 1 diabetes

BACKGROUND AND AIM: Vitamin K deficiency is common in persons with kidney disease, which is a known complication of diabetes. We aimed to assess the association of vitamin K status as reflected by plasma dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) with mortality, cardiovascular disease (CVD) and progression to end-stage kidney disease (ESKD) in persons with type 1 diabetes.

MATERIALS AND METHODS: We analysed plasma dp-ucMGP in stored baseline samples from a cohort of 667 persons with type 1 diabetes (baseline visit: 2009-2011). Information on mortality and CVD was obtained through linkage to registers. Cox-proportional hazards models were applied to estimate hazard ratios (HRs) of mortality, CVD and ESKD per one doubling of dp-ucMGP.

RESULTS: A total of 53 deaths were recorded during follow-up. Persons with higher dp-ucMGP (reflecting lower vitamin K status) had higher mortality in the unadjusted model (HR: 2.06 [95% confidence interval-CI: 1.22-3.45]), but not in the fully adjusted model (HR: 0.88 [95% CI: 0.44-1.73]). Particularly, adjustment for glomerular filtration rate and urinary albumin excretion rate attenuated the HR. A similar pattern was observed in unadjusted models for incidence of CVD (HR: 1.58 [95% CI: 1.03-2.42]) and risk of ESKD (HR: 7.62 [95% CI: 4.25-13.68]). In the fully adjusted models, the HRs became statistically insignificant.

CONCLUSION: In persons with type 1 diabetes, lower vitamin K status was associated with higher mortality, CVD and progression to ESKD, however, not after adjustment for other risk factors. Interventional studies are needed to elucidate the role of vitamin K in persons with type 1 diabetes.