Elsevier

Metabolism

Volume 60, Issue 7, July 2011, Pages 965-968
Metabolism

Low-salt diet increases insulin resistance in healthy subjects

https://doi.org/10.1016/j.metabol.2010.09.005Get rights and content

Abstract

Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium <20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium >150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 ± 12.5 years (range, 18-65) and with body mass index of 25.3 ± 4.0 kg/m2, were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 ± 1.6 vs 2.4 ± 1.7, P < .01). Serum aldosterone (21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL, P < .001), 24-hour urine aldosterone (63.0 ± 34.0 vs 9.5 ± 6.5 μg/d, P < .001), and 24-hour urine norepinephrine excretion (78.0 ± 36.7 vs 67.9 ± 39.8 μg/d, P < .05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation.

Introduction

Low dietary salt intake is recommended as one of the public health measures to decrease the risk of cardiovascular disease [1]. However, low-salt intake stimulates aldosterone production through activation of the renin-angiotensin-aldosterone system (RAAS) [2]. We recently demonstrated an association between aldosterone and insulin resistance (IR) in healthy subjects [3]. Moreover, sympathetic nervous system is activated by low-salt diet as shown by an increase in urine norepinephrine levels [4], [5]. Activation of the sympathetic nervous system may also increase IR [6]. Therefore, low dietary salt intake may be associated with an increase in IR. Previous studies on the effect of salt intake on IR in healthy subjects have shown contradictory results. Some studies showed an increase in IR [7], [8], whereas others found no such effect or a decrease in IR [9], [10], [11]. To investigate this further, we analyzed data from a large cohort of healthy subjects studied under carefully controlled conditions. Furthermore, we investigated whether the effect of salt intake on IR could be explained by known risk factors for IR.

Section snippets

Methods

This is an analysis of data collected during the studies conducted as part of the International HyperPath (Hypertensive Pathotype) cohort [12] and includes subjects from 3 sites: Boston, Salt Lake City, and Nashville. Study subjects included men and women aged 18 to 65 years who were generally free of any significant medical or psychiatric problems. The studies were approved by the Human Research Committee at each site, and informed consent was obtained. All participants were studied after 7

Results

We identified 227 subjects studied on both LS and HS diets. Seventy-five subjects were excluded from analysis because of urine sodium greater than 20 mmol/d on LS diet or less than 150 mmol/d on HS diet. One hundred fifty-two subjects were included in this analysis. The subjects were 39.1 ± 12.5 years old and included 55% women. Eighty percent of subjects were white. Subject characteristics and laboratory values obtained on LS and HS diets are shown in Table 1. Body mass index (BMI) and blood

Discussion

Our study shows that low salt intake is associated with higher IR. The effect of dietary salt intake on insulin sensitivity has been controversial. Some previous studies have shown an increase in IR with low-salt diet [7], [8], whereas others found no such effect or even a decrease in IR [9], [10], [11]. These discrepancies may be due to differences in study populations, levels of salt restriction, or study methods or to the relatively small sample size in previous studies of healthy

Acknowledgment

Funding: Supported by National Institutes of Health grant HL 087060.

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Author contributions: RG conceived the idea, analyzed and interpreted the data, and wrote the manuscript; GHW helped in interpretation of data and reviewed the manuscript; SH helped with statistical analysis; NB recruited patients and reviewed the manuscript; PNH recruited patients and reviewed the manuscript; and GKA helped in interpretation of data and revised the manuscript.

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