Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: A Mendelian Randomization Study

• Published in: Diabetes (New York, N.Y.) Vol. 68; no. 1; pp. 220 - 225
• Main Authors: Zwakenberg, Sabine R., Remmelzwaal, Sharon, Beulens, Joline W.J., Booth, Sarah L., Burgess, Stephen, Dashti, Hassan S., Imamura, Fumiaki, Feskens, Edith J.M., van der Schouw, Yvonne T., Sluijs, Ivonne
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.01.2019
• Subjects: Cancer; Chair Nutrition and Health over the Lifecourse; Clinical trials; Cohort Studies; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Europe; Genetic diversity; genetic predisposition to disease; Genetic Predisposition to Disease - genetics; genetic variation; Genotype; Global Nutrition; HNE Nutrition and Health over the Lifecourse; HNE Voeding en Gezondheid in de Levenscyclus; Humans; Mendelian Randomization Analysis; noninsulin-dependent diabetes mellitus; nutrition risk assessment; phylloquinone; Pleiotropy; Polymorphism, Single Nucleotide - genetics; Prospective Studies; relative risk; Risk Factors; Vitamin K 1 - blood; Vitamins; VLAG; Weight control; Wereldvoeding; Europe
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db18-0543

This study investigated the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes by using a Mendelian randomization (MR) approach. We used data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM), and the UK Biobank, resulting in 69,647 subjects with type 2 diabetes. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations. Inverse-variance weighted analysis was used to obtain a risk ratio (RR) for the causal relation between circulating phylloquinone concentrations and risk of type 2 diabetes. Presence of pleiotropy and the robustness of the results were assessed using MR-Egger and weighted-median analyses. Genetically predicted concentrations of circulating phylloquinone were associated with lower risk of type 2 diabetes with an RR of 0.93 (95% CI 0.89; 0.97) per every natural logarithm (Ln)-nmol/L–unit increase in circulating phylloquinone. The MR-Egger and weighted median analyses showed RRs of 0.94 (0.86; 1.02) and 0.93 (0.88; 0.98), respectively, indicating no pleiotropy. In conclusion, our study supports that higher circulating phylloquinone may be causally related with lower risk of type 2 diabetes, highlighting the importance of sufficient phylloquinone in the human diet.