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

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