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

心血管疾病（CVD）是全世界最常见的死亡原因，特别是随着社会老龄化，患病率不断上升。高饮食盐摄入和/或组织钠（Na+）积累与血压值升高有关。为了直接观察人类这些复杂的过程，我们实施了Na+磁共振成像（23NaMRI），并研究了各种电解质失衡患者的Na+储存。新的数据揭示了组织Na+储存和高血糖之间的联系。我们认为，血糖控制受损可能会导致人体组织中Na+稳态的改变。这两种“白色晶体”同时发生代谢改变可能最终导致血管损伤。一方面，2型糖尿病（T2DM）患者糖代谢受损会影响细胞外基质组成，从而改变组织Na+积累能力。另一方面，氧化应激导致线粒体呼吸链复合物的解耦可能导致细胞内外间隙的电解质紊乱。我们怀疑糖尿病患者的Na+超载至少部分是由细胞内Na+积累增强引起的。间质葡萄糖浓度的高度可变性可能是这一过程的关键。此外，我们假设组织Na+积累有助于T2DM患者的血管僵硬。我们也假设过量的钠离子储存在糖尿病患者是一个可逆的条件，因此易受治疗干预。我们提出了一个综合的项目，基于肾脏科和放射科之间的密切合作在UKER。在23Na-MRI技术增强的支持下，我们将对T2DM患者进行广泛的表型分析，包括他们的组织Na+负荷、连续血糖监测和详细的血管读数。各种新开发的23Na-MRI技术将应用于获取Na+存储的微环境信息（例如“松散结合”到蛋白质或游离Na+）。我们工作的长期目标是调查组织Na+储存的增加是否意味着糖尿病患者的独立心血管危险因素，其程度足以保证特定干预。

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.