Hypernetrimia and Diabetes connection

Abstract

High dietary sodium intake promotes urinary sodium and glucose excretion by elevating plasma adiponectin levels through PPARδ stimulation in adipose tissue. The resulting increase in adiponectin downregulates renal SGLT2, thereby reducing the reabsorption of both sodium and glucose—a protective mechanism that is weakened by hyperglycemia in diabetes. High sodium consumption is a major risk factor for hypertension in diabetic individuals, and promoting sodium excretion helps reduce cardiometabolic complications. However, the interaction between sodium intake and glucose homeostasis remains poorly understood. In this study, high sodium intake significantly increased natriuresis in wild-type mice, but this effect was blunted in adipose-specific PPARδ knockout mice and in diabetic mice. Activating PPARδ in perirenal fat—either through agonists or high salt intake—suppressed renal SGLT2 function via enhanced adiponectin production. Additionally, high salt-induced natriuresis was impaired in diabetes due to renal SGLT2 dysfunction. In type 2 diabetic patients with uncontrolled hyperglycemia, reduced natriuresis correlated with their plasma adiponectin levels. These findings reveal the distinctive role of the PPARδ/adiponectin/SGLT2 pathway in regulating sodium and glucose balance. High sodium intake increases type 2 diabetes risk by contributing to obesity, insulin resistance, and hypertension. For diabetic patients, limiting sodium to under 1,500 mg/day is recommended to manage blood pressure and reduce cardiovascular risk. Hypernatremia, most common among older adults, may also result from excessive urination due to high blood sugar, kidney disorders, vasopressin resistance, adrenal gland disorders, or excessive salt administration in hospitalized patients.