Impact of glucose metabolism on tissue sodium accumulation in diabetic patients and its relation to vascular stiffness

• Applicants: Dr. Anke Dahlmann; Professor Dr. Armin Nagel, Ph.D.
• Subject Area: Nephrology ; Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445440403

Cardiovascular disease (CVD) is the commonest cause of death worldwide and the prevalence is continuously rising particularly as societies age. High dietary salt intake and/or tissue sodium (Na+) accumulation is associated with elevated blood pressure values. To visualize these complex processes in humans directly, we implemented Na+ magnetic resonance imaging (23NaMRI) and investigated Na+ stores in patients developing various electrolyte imbalances. New data shed light on a link between tissue Na+ storage and hyperglycemia. We believe that impaired blood glucose control could in-and-of itself lead to altered Na+ homeostasis in human tissues. Concurrence of metabolic alterations on both these “white crystals” may culminate in vascular damage. On one hand, impaired glucose metabolism in type-2 diabetic (T2DM) patients affects extracellular matrix composition and may therefore change the capacity of tissue Na+ accumulation. On the other hand, decoupling of mitochondrial respiratory chain complex due to oxidative stress might lead to electrolyte disturbances between the intra- and extracellular space. We suspect that the Na+ overload in diabetic patients is, at least partially, caused by enhanced intracellular Na+ accumulation. A high variability of interstitial glucose concentration might be pivotal for this process. Furthermore, we hypothesize that tissue Na+ accumulation contributes to vascular stiffness in T2DM patients. We also hypothesize that excessive Na+ storage in diabetic patients is a reversible condition and therefore susceptible for therapeutic interventions. We propose a comprehensive project based on the close collaboration between the Departments of Nephrology and Radiology at UKER. Supported by the enhancement of 23Na-MRI technique, we will perform extensive phenotyping of T2DM patients including their tissue Na+ load, continuous glucose monitoring, and a detailed vascular readout. Various newly developed 23Na-MRI techniques will be applied to gain information about the micro-environment where Na+ is stored (e.g. “loosely bound” to protein or free Na+). The long-term goal of our work is to investigate whether increased tissue Na+ storage implies an independent cardiovascular risk factor for diabetic patients of sufficient magnitude to warrant specific intervention.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Christoph Kopp