High Sodium Intake Is Associated With Increased Glucocorticoid Production, Insulin Resistance and Metabolic Syndrome

R. Baudrand; C. Campino; C.A. Carvajal; O. Olivieri; G. Guidi; G. Faccini; P.A. Vöhringer; J. Cerda; G. Owen; A.M. Kalergis; C.E. Fardella

Disclosures

Clin Endocrinol. 2014;80(5):677-684. 

In This Article

Abstract and Introduction

Abstract

Objective High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS).

Patients and measurements We recruited 370 adults (18–85 years, BMI 29·3 ± 4·4 kg/m2, 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM).

Results Urinary sodium was correlated with UFC (r = +0·45, P < 0·001), cortisol THM (r = +0·41, P < 0·001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50–149 mEq/day) had higher UFC (P < 0·001), THM (P < 0·001), HOMA-IR (P = 0·04), HT (81% vs 50%, P < 0·001), MetS (69% vs 41%, P < 0·001) and lower adiponectin (P = 0·003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0·878) using four clinical variables: HS intake [OR = 5·6 (CI 2·3–15·3)], HOMA-IR [OR 1·7 (1·3–2·2)] cortisol THM [OR 1·2 (1·1–1·4)] and adiponectin [OR = 0·9 (0·8–0·9)], the latter had a protective effect.

Conclusions High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.

Introduction

Central obesity, hypertension, derangement of glucose and lipid metabolism are hallmarks of the metabolic syndrome (MetS), which is highly prevalent worldwide.[1] The mechanisms leading to MetS are not fully understood, but several complementary hypotheses have been proposed including insulin resistance (IR), adipose tissue dysregulation, inadequate aldosterone suppression and increased cortisol production.[2,3]

Populations with liberal salt intake have higher incidences of HT and cardiovascular events, and its related health outcomes are associated with high medical costs.[4] Moreover, high sodium intake has been reported to be an important clinical factor implicated in salt sensitivity in MetS.[5] There is also a reported relationship between increased sodium intake and insulin resistance (IR) and type 2 diabetes mellitus (T2DM).[6] Numerous mechanisms have been postulated to explain why liberal sodium intake contributes to metabolic disorders, with special emphasis in inadequate aldosterone suppression and increased mineralocorticoid receptor (MR) activation by factors other than aldosterone.[7,8]

We and others have shown that obesity and MetS, when correctly excluding subclinical Cushing's syndrome, are associated with increased levels of urinary glucocorticoid (GC) metabolites, but normal plasma values.[3,9,10] Moreover, GC metabolites levels are correlated with HT, IR and dyslipidaemia, resembling metabolic abnormalities observed with liberal salt intake.[3] Although the relationship between high sodium diet and GC production has been less studied than aldosterone, it has been described that high sodium diet increases local GC production in a rodent model and that salt loading increases urinary cortisol and sodium restriction decreases cortisol excretion in human studies.[11,12,13]

The aim of the present study was to evaluate a possible dysregulation of cortisol production secondary to liberal sodium intake that could have an essential role in MetS and obesity-related metabolic disorders.

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