Comparison of endothelial function and sympathetic nervous system activity along the glucose continuum in individuals with differing metabolic risk profiles and low dietary sodium intake.

OBJECTIVE: Low sodium intake may trigger sympathetic nervous system (SNS) activation and endothelial dysfunction. Studies have not explored these associations along the glucose continuum. Accordingly, we compared endothelial function and SNS activity in individuals with low sodium intake and differing categories of metabolic risk along the glucose continuum. We hypothesized that low sodium intake is associated with (1) impairment of endothelial function and (2) higher SNS activity in individuals with higher metabolic risk. RESEARCH DESIGN AND METHODS: In this prospective observational study, participants (n=54) with low sodium intake (single 24 hours urine sodium excretion <150 mmol/24 hours) were categorized based on oral glucose tolerance testing as: normal glucose tolerance (NGT, n=10), impaired glucose tolerance (IGT, n=15), treatment naive type 2 diabetes (T2D-) (n=12) or treated type 2 diabetes (T2D+) (n=17). We assessed endothelial function using pulse amplitude tonometry (PAT) derived reactive hyperemic index and PAT ratio; arterial stiffness via augmentation index; muscle sympathetic nerve activity (MSNA) using microneurography; cardiac baroreflex; heart rate; blood pressure; glycosylated hemoglobin A1c (HbA1c) and lipid profile. RESULTS: Mean (SD) sodium excretion was 110.6 (26) mmol/24 hours. Compared with NGT, IGT and T2D-, the T2D+ group had lower MSNA (p=0.005), PAT ratio (p=0.04) and baroreflex sensitivity (p=0.0002) and an augmented heart rate (p=0.02). The T2D+ group had appropriate mean (SD) glycemic (HbA1c 7.2 (1.72)%), total cholesterol (4.2 (1.0) mmol/L), low-density lipoprotein (2.2 (1.0) mmol/L) and blood pressure (systolic 136 (13), diastolic 78 (12)) (mm Hg) control. CONCLUSIONS: Individuals with T2D+ have impaired endothelial and baroreflex function, despite low sodium intake, appropriately managed cardiometabolic risk factors and lower SNS activity, compared with others along the glucose continuum. Whether low sodium intake is associated with modulation of the sympathovascular profile in T2D requires further investigation.

Sodium Intake, Circulating Microvesicles and Cardiovascular Outcomes in Type 2 Diabetes.

There is ongoing debate surrounding the complex relationship between dietary sodium intake and cardiovascular morbidity and mortality. The existing literature consists largely of observational studies that have demonstrated positive, negative, U-/J-shaped or unclear associations between sodium intake and cardiovascular outcomes. Our group and others have previously demonstrated an inverse relationship between dietary sodium intake and cardiovascular outcomes in people with type 2 diabetes. Increased activity of the renin-angiotensin-aldosterone system and sympathetic nervous system is postulated to contribute to these paradoxical findings through endothelial dysfunction, a precursor to the development of cardiovascular disease. Microvesicles are submicron (0.1 - 1.0µm) vesicles that form during cellular activation, injury or death with endothelial microvesicles being recognized markers of endothelial dysfunction. They are pathologically elevated in a variety of vascular-related conditions including type 2 diabetes. Lower habitual sodium intake in type 2 diabetes has been associated with higher pro-coagulant platelet microvesicles levels but not with endothelial microvesicles. Research utilizing endothelial microvesicles to evaluate the mechanistic relationship between dietary sodium intake and adverse cardiovascular outcomes in type 2 diabetes remains scarce.