The association between pulse wave velocity and peripheral neuropathy in patients with type 2 diabetes mellitus

Diabetic peripheral neuropathy (DPN) is the most common diabetic complication, affecting up to half of the patients with type 2 diabetes mellitus (T2DM). Increased aortic stiffness, measured with the carotid-femoral pulse wave velocity (PWV), has been associated with incidence of cardiovascular disease independently of traditional risk factors. Previous data showed associations between risk factors for macroangiopathy and DPN in diabetes. However, the association between PWV and DPN is not well known. In this study we examined the association between PWV and presence as well as severity of DPN in subjects with T2DM.

A total of 381 patients with T2DM were recruited. Participants were classified as having DPN and not having DPN. PWV was measured at the carotid-femoral segment with a non-invasive method using applanation tonometry. DPN was assessed by determination of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS).

A hundred and seven participants (28.1%) had DPN. Patients with DPN were significantly more often male and older, had longer diabetes duration, higher height, larger waist circumference, higher systolic arterial blood pressure (SBP) and higher PWV (all P<0.05). Furthermore, participants with DPN were treated more often with statins and had lower low density lipoprotein cholesterol; in addition, they were treated more often with antiplatelets, b-blockers and insulin than those without DPN. Univariative logistic regression analysis demonstrated that presence of DPN was significantly associated with age, male gender, longer diabetes duration, height, waist circumference, SBP, PWV, dyslipidemia, HbA1c, retinopathy, nephropathy and peripheral arterial disease. Multivariate logistic regression analysis, after adjustment for age, gender, waist circumference, SBP, nephropathy and use of b-blockers, demonstrated that the odds [OR (95% confidence intervals)] of peripheral neuropathy were associated significantly and independently only with diabetes duration [1.044 (1.009-1.081), P=0.013], height [1.075 (1.041-1.110), P<0.001], HbA1c [1.468 (1.164-1.851), P<0.001], PWV [1.174 (1.054-1.309), P=0.004], dyslipidemia [1.941 (1.015-3.713), P=0.045], retinopathy [4.426 (2.217-8.837), P<0.001] and peripheral arterial disease [4.658 (2.264-9.584), P<0.001]. In addition, multivariate linear regression analysis, after controlling for age, gender, diabetes duration, SBP, HbA1c and nephropathy, demonstrated that an increased NDS was significantly and independently associated with height [standardized regression coefficient (beta=0.229, P<0.001)], PWV (beta=0.197, P<0.001), retinopathy (beta=0.268, P<0.001) and peripheral arterial disease (beta=0.374, P<0.001).

Increased PWV is associated strongly and independently not only with the presence but also with the severity of DPN in patients with T2DM, irrespective of known risk factors.