Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function

Abstract

We have studied the temporal relationship of plasma von Willebrand Factor (vWF), a marker of endothelial damage, with the development of complications in 63 young diabetic patients (56 of whom were insulin-dependent) who took part in a prospective study. Results are presented from baseline to follow-up. In the group as a whole, no significant changes were found in any autonomic function tests, temperature discrimination threshold or nerve conduction velocities. Median motor and peroneal latency were significantly increased, while median motor, peroneal motor and sural sensory potentials were significantly decreased at follow-up compared with baseline (p < 0.001). There was a significant fall in mean plasma vWF antigen and ristocetin co-factor activity in the entire group. Within the group, we identified eight patients whose peroneal motor and sural sensory conduction velocities had decreased by over 2 ms-1. In these patients (Group A), baseline vWF antigen and activity were significantly higher than in the rest of the patients (Group B), (p = 0.04) and vWF antigen was still significantly higher after 3 years (p = 0.02). There were no differences between the groups in incidence of retinopathy, urinary albumin excretion rate or macrovascular disease. To assess the influence of glycaemic control on vWF, we first compared a matched group (C) of diabetic patients with similar HbA1 to that of group A, but with normal nerve conduction velocities: vWF was still significantly higher in group A compared with group C (p = 0.02). Furthermore, hierarchical regression showed that vWF predicted deteriorating nerve function independently of glycaemic control or the type of diabetes. Endothelial dysfunction may be associated with development of peripheral neuropathy in young diabetic patients.

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration

“…Our previous study using power spectral analysis of heart rate variation [29] indicated that diabetic patients with neuropathic foot ulceration had greater impairment of cardiac autonomic activity, including both vagus and sympathetic nerves, than diabetic patients with neuropathy but no history of ulceration. A previous study also reported that elevated vWF antigen predicted deterioration in peripheral nerve function in diabetic patients [30]. Taken together, the correlation of plasma vWF concentrations with various quantitative neurologic tests in the present study suggests that elevation of plasma vWF may be associated with the development of diabetic neuropathic foot ulceration.…”

Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease

“…In recently diagnosed patients with diabetes followed for 3 years, higher vWF levels predicted a subgroup of patients with diabetes who subsequently developed deficits in lower limb nerve conduction velocity (91). This finding suggests that endothelial dysfunction may predispose patients with diabetes to impairments in peripheral neural conduction.…”

“…This finding suggests that endothelial dysfunction may predispose patients with diabetes to impairments in peripheral neural conduction. Because none of the patients in this sample developed deficits in ANS function, further follow-up is expected to clarify whether elevated vWF will similarly predict future autonomic neuropathy (91).…”

Effect of Insulin on von Willebrand Factor Release in Normal and Diabetic Subjects: In Vivo and In Vitro Studies

“…To date, it has been difficult to determine whether this increase in vWf was the consequence of vascular disease or preceded the occurrence of these complications. It has recently been reported that vWf appeared to be a predictive nephropathy and neuropathy marker in type 1 diabetic patients [3,4]. These observations indicate that endothelial dysfunction may precede the onset of diabetic microangiopathy.…”