Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes

Context: Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D). Objective: To 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. Design: We conducted a randomized, double-blinded, placebo-controlled crossover trial. Setting: The study took place in a tertiary referral diabetes outpatient clinic. Participants: Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included. Intervention: Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered. Main outcome measures: The 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. Results: Compared 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). Conclusions: In 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.