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Serum vitamin K1 associated to microangiopathy and/or macroangiopathy in individuals with and without diabetes
  1. Ida Bøgh Andersen1,2,
  2. Claus Lohman Brasen1,2,
  3. Hashmatullah Nasimi1,3,
  4. Maria Stougård4,
  5. Mette Bliddal4,
  6. Anders Green4,
  7. Anne Schmedes1,
  8. Ivan Brandslund1,2,
  9. Jonna Skov Madsen1,2
  1. 1Department of Clinical Biochemistry and Immunology, Lillebælt Hospital, Vejle, Denmark
  2. 2Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
  3. 3Institute for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
  4. 4OPEN—Open Patient data Explorative Network, Department of Clinical Research, University of Southern Denmark and Odense University Hospital, Odense, Denmark
  1. Correspondence to Dr Jonna Skov Madsen; jonna.skov.madsen{at}


Objective Vitamin K has proposed beneficial effects on cardiovascular health. We investigated whether serum vitamin K1 was associated with prevalence of microangiopathy and/or macroangiopathy.

Research design and methods Serum vitamin K was quantified in 3239 individuals with and 3808 without diabetes enrolled in Vejle Diabetes Biobank (2007–2010). Each individual was assessed for microangiography and macroangiopathy at enrollment based on registered diagnoses in the Danish National Patient Registry according to the International Classification of Disease 8 (1977–1993) and 10 (since 1994). Using multinomial logistic regression, relative risk ratios (RRRs) were calculated within each group of individuals with and without diabetes. RRRs were estimated for microangiopathic/macroangiopathic status compared with individuals without complications as a function of 1 nmol/L increments in K1. Adjustment for potential confounders was also performed.

Results Vitamin K1 (median) varied 0.86–0.95 nmol/L depending on diabetes, microangiopathic and macroangiopathic status. In individuals with diabetes, the crude RRR for only having microangiopathy was 1.05 (95% CI 0.98 to 1.12) and was found significant when adjusting 1.10 (95% CI 1.01 to 1.19). RRR for having only macroangiopathy was 0.89 (95% CI 0.77 to 1.03) and was again significant when adjusting 0.79 (95% CI 0.66 to 0.96). In individuals without diabetes, adjustments again led to similar estimates that was not significant. The adjusted RRR for having only macroangiopathy was 1.08 (95% CI 0.98 to 1.19).

Conclusions Serum vitamin K1 levels were associated with microangiopathic and macroangiopathic status in individuals with diabetes, but considered of no clinical relevance. The clinical value of other candidate markers for vitamin K status needs to be evaluated in future studies.

  • microangiopathy
  • macroangiopathy
  • vitamins

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  • Contributors All contributors meet the criteria for authorship and are listed in the manuscript. IBA, CLB, AG, MB and JSM conceived and designed the study. Vitamin K1 analysis was carried out by IBA, HN and AS. Data management was done by MS and IBA. Statistical analysis, interpretation and first draft of the manuscript were prepared by IBA. IBA, CLB, MB, AG, IB and JSM revised the manuscript for intellectual content and all authors approved the manuscript for submission. JSM is the guarantor of the study.

  • Funding This work was supported by Department of Regional Health Research, The Faculty of Health Science, The University of Southern Denmark (SDU), Denmark and Region of Southern Denmark who each granted a 1-year PhD scholarship. The last year of PhD salary was funded by KEJ Fond, Copenhagen, Denmark.

  • Disclaimer The research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Danish Data Protection Agency (J. no. 2006-53-1385, J. no. 16/13707, J. no 16/28063) and ethical approved by The National Committee on Health Research Ethics and The Regional Committees on Health Research Ethics for Southern Denmark in Denmark (J. no. 2008-58-0035; additional protocol for this project: project-ID S-20080097, authorization no. 44010). All blood samples and data were handled anonymously.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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