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MRC DTP 4 Year PhD Programme: Metformin-associated B12 deficiency and cognitive function in Type 2 Diabetes

  • Full or part time

    Dr A Doney
  • Application Deadline
    Saturday, January 11, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

This project is offered as part of the University of Dundee 4-year MRC DTP Programme “Quantitative and Interdisciplinary approaches to biomedical science”. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its very high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK. A wide range of projects are available within this programme crossing exceptional strengths in four key areas: Infection and Disease; Responses to Cellular Stresses; Development, Stem Cells and Neurobiology; and Big Data and Translation. All students on this programme will receive training in computational biology, mathematical biology and statistics to equip with the quantitative skills in tackling complex biological questions. In the 1st year, students will carry out 3 rotation projects prior to selection of the final PhD project.

Metformin is the first line treatment for type 2 diabetes (T2D). T2D patients have lower vitamin B12 levels in their blood after taking metformin. It is not clear whether this decrease in vitamin B12 causes any harm. Vitamin B12 is essential to normal energy production in all cells of the body and especially cells in the brain. Our preliminary data suggest that patients who are on metformin and a B12 supplement have better cognitive function, a term referring to things like memory, the ability to learn etc., when compared to patients on metformin alone. In the current project, we plan to study whether metformin-caused B12 decline compromises cognitive function in Scottish T2D patients. The epidemic of Type 2 diabetes (T2D) in Scotland is on the rise. It is estimated that metformin is routinely prescribed to more than two hundred thousand patients with diabetes in Scotland. The association between metformin use and low vitamin B12 has been supported by many lines of evidence. Yet its clinical significance and underlying mechanisms of metformin-associated B12 deficiency still await clarifications. We have preliminary data suggesting that vitamin B12 supplementation improves cognitive function of metformin-treated T2D patients. These data are promising and if proven true, it will have massive impact in changing the treatment regime and guidance of T2D patients. However, these data were generated using the NHANES (National Health and Nutrition Examination Survey) programme, a health and nutritional study for people in the US. Whether these preliminary results hold true to people in Scotland and in the UK is unknown. Moreover, the mechanistic study of metformin-associated B12 deficiency in cell/animal model systems is limited. In the current proposed work, we plan to extend our preliminary approach and finding to Scottish population using the resources of Tayside and Fife Scottish Care Information-Diabetes Collaboration (SCI-DC). Furthermore, we propose to investigate the genetic components of the association between metformin and B12 deficiency as well as the underlying mechanisms by which metformin decreases vitamin B12 levelsin model systems.


References

References

1.M. A. Ahmed, Metformin and Vitamin B12 Deficiency: Where Do We Stand? J Pharm Pharm Sci19, 382-398 (2016).

2.Q. Liu, S. Li, H. Quan, J. Li,Vitamin B12 status in metformin treated patients: systematic review. PLoS One9, e100379 (2014).

3.F. Cabreiroet al., Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell153, 228-239 (2013).

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