• Sara Baqar, Yee Wen Kong, Angela X Chen, Christopher O'Callaghan, Richard J MacIsaac, Maree Bouterakos, Gavin W Lambert, George Jerums, Elisabeth E Lambert, and Elif I Ekinci.
• Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.
• J. Clin. Endocrinol. Metab. 2020 Apr 1; 105 (4).

ContextLower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D).ObjectiveTo determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo.DesignWe conducted a randomized, double-blinded, placebo-controlled crossover trial.SettingThe study took place in a tertiary referral diabetes outpatient clinic.ParticipantsTwenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included.InterventionSalt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered.Main Outcome MeasuresThe primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity.ResultsCompared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07).ConclusionsIn people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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