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

Abstract

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.

Reactive Hyperemia and Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Patients: A Systematic Review of Randomized and Nonrandomized Clinical Trials

“…Of the articles reviewed herein, five showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy [15,30,33,57,58], while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls [59]. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia (PSRH) between normal subjects and diabetic non-smokers [43].…”

“…Diabetic autonomic neuropathy (DAN) is a complicated heterogeneous disorder that affects the autonomic neurons of the peripheral nervous system [12]. Subclinical autonomic dysfunction can occur within 1-2 years of the diagnosis of diabetes mellitus [11,[13][14][15], and patients remain asymptomatic until well after the onset of diabetes [9,11,13,14]. Poor glycemic control, older age, a longer duration of diabetes, female gender, and obesity are major risk factors for the development and progression of this disease [12].…”

“…Subjects with CAN have a significantly reduced overall HRV compared to those without the disorder, with a mainly parasympathetic impairment appearing to precede sympathetic dysfunction [3,29,34]. Diabetic patients have been reported to exhibit sympathetic hyperactivity and an increased resting heart rate, although other authors observed low sympathetic nervous system (SNS) activity [15]. Another study suggested that sympathetic dysfunction may precede parasympathetic dysfunction, as assessed by HRV [7].…”

“…Considering that CAN dysfunction occurs in the early stages of diabetes and that multifactorial interventions can delay its development [7,15,29], a simple and effective tool for the early diagnosis of CAN is needed to improve the prognosis and quality of life of people with diabetes [7,29].…”

Letter: Effects of Dapagliflozin on Endothelial Function, Renal Injury Markers, and Glycemic Control in Drug-Naïve Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019:43:711–7)

“…The interconnection between T2DM and endothelial dysfunction has been established a long time ago, with the latter representing an initial step towards the development and progression of cardiovascular disease [2]. Recent data suggest that patients with T2DM feature an impaired endothelial function, even in the context of well-controlled cardio-metabolic risk factors and low sodium intake, compared to normal and impaired glucose tolerance subjects [3].…”