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

心血管疾病(CVD)是世界范围内最常见的死亡原因，其患病率不断上升，特别是随着社会的老龄化。高食盐摄入量和/或组织钠(Na+)蓄积与血压升高有关。为了直接在人体内可视化这些复杂的过程，我们实施了Na+磁共振成像(23NaMRI)，并研究了出现各种电解质失衡的患者的Na+储存情况。新的数据揭示了组织中钠离子储存和高血糖之间的联系。我们认为，血糖控制受损本身可能会导致人体组织中Na+稳态的改变。这两种“白色晶体”的代谢改变同时发生，可能最终导致血管损伤。一方面，2型糖尿病(T2 DM)患者糖代谢受损影响细胞外基质组成，从而改变组织Na+蓄积能力。另一方面，氧化应激导致线粒体呼吸链复合体的解偶联，可能导致细胞内外空间的电解质紊乱。我们怀疑糖尿病患者的Na+超载至少部分是由细胞内Na+蓄积增加引起的。间质葡萄糖浓度的高度变异性可能是这一过程的关键。此外，我们假设组织中Na+的积聚对T2 DM患者的血管僵硬有贡献。我们还假设糖尿病患者过多的Na+储存是一种可逆的情况，因此容易受到治疗干预的影响。我们在UKER肾病科和放射科密切合作的基础上提出了一个全面的项目。在23Na-MRI技术的支持下，我们将对T2 DM患者进行广泛的表型鉴定，包括组织Na+负荷、连续血糖监测和详细的血管读数。各种新开发的~(23)Na-MRI技术将被应用于获得有关存储Na+的微环境的信息(例如，与蛋白质或游离Na+的“松散结合”)。我们工作的长期目标是调查组织中增加的Na+储存是否意味着对于fi程度足够大的糖尿病患者来说，一个独立的心血管危险因素，以保证特殊的fic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.