High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals

Background and aims: High sodium intake is associated with obesity and insulin resis-tance, and high extracellular sodium content may induce systemic inflammation, leading to car-diovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association.Methods and results: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respec-tively. In obese individuals, insulin sensitivity negatively correlated with muscle (r =-0.45, p = 0.01) and skin sodium (r =-0.46, p = 0.01). In interaction analysis among obese individ-uals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In inter-action analysis of the entire cohort, the association between muscle sodium and insulin sensi-tivity was stronger with increasing levels of serum leptin (p-interaction = 0.01).Conclusions: Higher muscle and skin sodium are associated with insulin resistance in obese pa-tients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation re-mains to be examined in future studies.

Automated summary

This study investigates the association between high tissue sodium accumulation and obesity-related insulin resistance, and explores the potential role of excess tissue sodium accumulation in systemic inflammation and leptin dysregulation. The results show that higher muscle and skin sodium content are associated with insulin resistance in obese patients.