Role of magnesium and thiamine deficiency-mediated carbonyl stress in diabetic neuropathy and kidney disease

• Applicants: Dr. Alexandra Chadt; Dr. Alexander Strom
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 496664790

Diabetic neuropathy (DN) and diabetic kidney disease (DKD) are highly prevalent microvascular complications of diabetes encountered in 30-40% of people with type 1 or type 2 diabetes. Over the last two decades, evidence linking methylglyoxal-mediated carbonyl stress to diabetic microvascular complications has accumulated. Transketolase, as the main thiamine target in the pentose phosphate pathway, pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase require both thiamine and magnesium for catalytic activity. Based on the literature and our findings thiamine deficiency, hypomagnesemia and the resulting carbonyl stress contribute to the development of DN and DKD. In the proposed study, we aim to investigate the effects of combined magnesium and thiamine supplementation as a new therapeutic approach to protect from methylglyoxal-mediated carbonyl stress and thereby prevent from DN and DKD. The results of this experimental study could have a major impact on the design and outcome of clinical trials assessing the potential disease modifying effects of thiamine or its derivatives in DN and DKD.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Dan Ziegler