Metformin-associated B12 deficiency and cognitive function in Type 2 Diabetes

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 levels in model systems.

References

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