Abstract

Objective: Diabetic large nerve fibre dysfunction, as measured by vibration perception threshold (VPT) predicts foot ulceration, amputation and mortality. Thus, determination of modifiable risk factors is of great clinical importance.

Research Design and Methods: We assessed 1407 patients with type 1 diabetes and normal VPT participating in the EURODIAB Prospective Complications Study, at baseline mean age 32.7±10.2 years; mean diabetes duration 14.7±9.3 years; and mean follow-up of 7.3±0.6 years. VPT was measured using biothesiometry on the right big toe and medial malleolus. An abnormal result was defined as >2SD from the predicted mean for the patient's age.

Results: An abnormal VPT was associated with an increased incidence of gangrene, amputation, foot ulceration, leg bypass or angioplasty and mortality (p≤0.02). The incidence of abnormal VPT was 24% over the 7.3 year follow-up. Duration of diabetes and HbA_1c significantly influenced the incidence of abnormal VPT (p<0.0001). After correction for these, established risk factors for cardiovascular disease including, male sex (p=0.0004), hypertension (p<0.0001), total cholesterol (p=0.002), LDL cholesterol (p=0.01), smoking (p<0.0001), weight (p<0.0001); and diabetic complications (retinopathy (p=0.0001), nephropathy (p=0.01) and autonomic neuropathy (p=0.001)) were all found to be significant risk factors. A previous history of cardiovascular disease doubled the incidence of abnormal VPT.

Conclusions: This prospective study indicates that cardiovascular risk factors predict development of large fibre dysfunction. This may account for the high mortality rate in patients with abnormal VPT, and emphasises the importance of an early determination of VPT to detect sub-clinical neuropathy, and to address cardiovascular risk factors.