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Nutritional biomarkers to advance understanding of association between diet and type 2 diabetes

Periodic Reporting for period 1 - NUTBIO-DIAB (Nutritional biomarkers to advance understanding of association between diet and type 2 diabetes)

Reporting period: 2016-03-01 to 2018-02-28

Diet and nutrition are crucial for the prevention of chronic diseases, such as type 2 diabetes, but measurement error in self-report dietary assessment has posed a major challenge in the research on the links between dietary factors and health outcomes. Compared to the self-reported data that is traditionally used for dietary assessment, blood measures that reflect dietary intake (nutritional biomarkers) can provide an objective measurement of nutritional status and dietary intake.

The systematic use of nutritional biomarkers has the potential to meaningfully advance the scientific understanding of the link between dietary factors and type 2 diabetes. This is important for the public and society at both the individual and collective level, given the translational value of diet and nutrition research to people’s daily life, affecting individuals’ dietary choice and long-term health status. For type 2 diabetes this is critical, as the global burden of this condition remains a major public health challenge, with no sign of the slowing down of the rise in its prevalence worldwide.

This project had the related aims (1) to train and upskill the fellowship recipient to become a mature/independent researcher and be a future leader in the field of nutritional epidemiology, and (2) to do so, by working specifically with the unprecedented resource of nutritional biomarkers that has been generated within the framework of the EU FP6 funded EPIC-InterAct study across 8 European countries to improve the precision of dietary assessment for investigating the relationship between dietary factors and diabetes risk. The use of biomarkers also opens the possibility to investigate causal associations using genetic-based approaches.

Using the newly measured data of the biomarkers plasma vitamin C, several plasma carotenoids and vitamin D metabolites in the EPIC-InterAct study, substantial progress has been made to achieve the project goals:

• Data preparation included detailed quality control procedures for the measured biomarkers, and the research fellow led a set of recommendations on the appropriate use of these data that will enable optimal analysis by other researchers.
• The research fellow completed statistical analyses; shared and discussed the results with scientific working groups across the InterAct consortium; presented the emerging findings from this project at scientific meetings; and several draft manuscripts are in progress.
• The research fellow received high level training in nutritional epidemiology and genetic epidemiology.

The knowledge generated from the project will be of importance to advance the understanding of the relationship between diet, nutritional biomarkers and diabetes risk, particularly in European populations.
The fellowship recipient performed the work using the newly generated nutritional biomarker data from the EPIC-InterAct study. Specific work included the following:

• Set up of the pipeline to conduct detailed quality control, data cleaning and recommendations for the use of the nutritional biomarker data in the EPIC-InterAct study.
• Set up of working groups for the project, collaboration with the working groups for drafting and finalising the analysis plan for the project as a whole and for individual draft manuscripts generated from the project.
• Leading collaborations with scientists both internal and external to the host institution, to obtain data from other studies (additional to EPIC-InterAct study) to maximise statistical power for the genetic epidemiology analyses.
• Completion of the analyses examining the geographical distribution and demographic, social, lifestyle and dietary determinants of the blood vitamin C, carotenoids and vitamin D biomarkers across European countries.
• Completion of the analyses on the link between blood vitamin C, carotenoids and vitamin D biomarkers with risk of developing type 2 diabetes in European populations.
• Completion of genome-wide association analyses (GWAS) for genetic discovery to identify genes affecting the levels of the above blood biomarkers, and analyses of their causal association with type 2 diabetes using the genetic tools.

Dissemination activities
Emerging findings were presented at the MRC Epidemiology Unit, University of Cambridge 2017 Research Day and the European Association for the Study of Diabetes (EASD) 2017 Annual Meeting.

Part of the results on genetics (GWAS) of vitamin D metabolites contributed to a large international consortium, which identified two novel genes, and the results were published recently (Nature Communication 2018 doi:10.1038/s41467-017-02662-2).

There is a forthcoming presentation (oral) of our findings on vitamin D metabolites and type 2 diabetes at the annual meeting of American Society of Nutrition in Boston, June 2018.

Based on the above activities several manuscripts, currently in draft form, will be published in peer-reviewed scientific journals.

As a related activity on nutritional biomarkers, the fellowship recipient published a manuscript on the association between circulating individual saturated fatty acids and markers of cardiometabolic risk (Zheng J et al, BMC Med 2017,15:203.doi: 10.1186/s12916-017-0968-4).
This fellowship project has contributed to advancing the understanding of the link between dietary factors and new-onset type 2 diabetes by the analysis of nutritional biomarkers on a previously unprecedented scale, including more than 12,000 new-onset cases of type 2 diabetes and a large representative sub-cohort across multiple European countries in the InterAct project.

The project enabled the researcher to obtain advanced training in epidemiology, nutritional epidemiology, genetic epidemiology and statistics, analysing large-scale cohort data and applying advanced statistical methods. He extended his scientific networks considerably, having worked with collaborators across multiple European countries. The project helped to substantially increase the capacity of the researcher to become a mature and independent scientist, leading to a forthcoming appointment as a senior scientist (assistant professor) at a prestigious academic institution in China. It is anticipated that in time the researcher will be among major future leaders in the field of nutritional epidemiology in China. The strong link fostered with the supervisor (Professor Nita Forouhi) and the host institution (MRC Epidemiology Unit, University of Cambridge, U.K.) will facilitate future collaborative working for better science, including Chinese populations to understand differences in disease risk across and between populations.

The researcher has already engaged in a number of dissemination activities based on the findings of the project (such as presentations at the MRC Epidemiology Unit Research Day 2017, and the EASD meeting, 2017). Further planned dissemination includes an oral presentation at the annual meeting of the American Society of Nutrition, one of the most influential nutrition societies globally. The researcher also plans to attend other scientific conferences and public engagement events to promote the results of the project. Several scientific manuscripts are in preparation and will have scientific impact through publication in scientific journals. The findings from this project are of direct relevance for public health.
Jusheng working at MRC Epidemiology Unit, University of Cambridge
Jusheng working at MRC Epidemiology Unit, University of Cambridge
Jusheng working at MRC Epidemiology Unit, University of Cambridge