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

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Item Type:	Article
Title:	High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals
Creators Name:	Ertuglu, L., Sahinoz, M., Alsouqi, A., Deger, S.M., Guide, A., Stewart, T.G., Pike, M., Robinson-Cohen, C., Akwo, E., Pridmore, M., Crescenzi, R., Madhur, M.S., Harrison, D.G., Luft, F.C., Titze, J. and Ikizler, T.A.
Abstract:	BACKGROUND AND AIMS: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular 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 (23)Na 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, respectively. 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 individuals, 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 interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity 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 patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. Clinicaltrials.gov registration: NCT02236520.
Keywords:	Blood Glucose, Cross-Sectional Studies, Inflammation, Insulin, Insulin Resistance, Leptin, Obesity, Sodium
Source:	Nutrition Metabolism and Cardiovascular Diseases
ISSN:	0939-4753
Publisher:	Elsevier
Volume:	33
Number:	7
Page Range:	1398-1406
Date:	July 2023
Additional Information:	Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University.
Official Publication:	https://doi.org/10.1016/j.numecd.2023.03.024
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