Autonomic Neuropathy and Endothelial Dysfunction in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus

Autonomic neuropathy is one of the most common complications of diabetes mellitus (DM). The etiology of autonomic impairment is not well-understood, yet. There is need for studies to investigate the cause-effect relationships of inflammation and/or endothelial dysfunction and diabetic autonomic neuropathy. Only a few reports have mentioned autonomic neuropathy in individuals with impaired glucose tolerance (IGT), previously. Furthermore, the association between the plasma markers of endothelial dysfunction (von Willebrand factor (vWF), soluble E-selectin) and autonomic neuropathy in patients with IGT or DM has not been studied before. In this study, we aimed to investigate the correlation between plasma markers of endothelial dysfunction and autonomic neuropathy in patients with IGT or type 2 DM (T2DM). In this case-control study, 25 IGT patients, 25 T2DM patients with autonomic symptoms, and 30 controls were included. Demographical data, HbA1c, vWF, and soluble E-selectin (sE-selectin) levels were analyzed. Sympathetic skin response (SSR) and heart rate variability (HRV) were used as the indicator of autonomic activity. Plasma levels of HbA1c, vWF, and sE-selectin were higher in patients with IGT than the controls; patients with T2DM had higher levels than both the controls and the patients with IGT. SSR measures were similar among the groups. However, higher number of T2DM patients had absent plantar SSR than controls. HRV analysis at rest revealed lower standard deviation of R-R interval, coefficient of variation of R-R interval, low-frequency (LF) power and total power in patients with IGT and T2DM than the controls. In addition, HRV analysis at deep breathing showed lower high-frequency (HF) power in IGT group. LF:HF ratio was lower in both patient groups at rest. No strong correlation was found between the levels of HbA1c, vWF, sE-selectin, HRV, and SSR measures. Our results support that endothelial dysfunction is evident in individuals with IGT or T2DM and HRV is impaired in early stages in the course of T2DM. However, increased levels of biomarkers of endothelial damage do not correlate with HRV or SSR. More studies are needed to clarify the disease pathogenesis and its clinical correlates. Impaired HRV in T2DM could be due to mechanisms other than endothelial dysfunction.