Abstract

Aims/hypothesisWe aimed to examine associations of cardiometabolic risk factors, and (pre)diabetes, with (sensorimotor) peripheral nerve function.MethodsIn 2401 adults (aged 40–75 years) we previously determined fasting glucose, HbA1c, triacylglycerol, HDL- and LDL-cholesterol, inflammation, waist circumference, blood pressure, smoking, glucose metabolism status (by OGTT) and medication use. Using nerve conduction tests, we measured compound muscle action potential, sensory nerve action potential amplitudes and nerve conduction velocities (NCVs) of the peroneal, tibial and sural nerves. In addition, we measured vibration perception threshold (VPT) of the hallux and assessed neuropathic pain using the DN4 interview. We assessed cross-sectional associations of risk factors with nerve function (using linear regression) and neuropathic pain (using logistic regression). Associations were adjusted for potential confounders and for each other risk factor. Associations from linear regression were presented as standardised regression coefficients (β) and 95% CIs in order to compare the magnitudes of observed associations between all risk factors and outcomes.ResultsHyperglycaemia (fasting glucose or HbA1c) was associated with worse sensorimotor nerve function for all six outcome measures, with associations of strongest magnitude for motor peroneal and tibial NCV, βfasting glucose = −0.17 SD (−0.21, −0.13) and βfasting glucose = −0.18 SD (−0.23, −0.14), respectively. Hyperglycaemia was also associated with higher VPT and neuropathic pain. Larger waist circumference was associated with worse sural nerve function and higher VPT. Triacylglycerol, HDL- and LDL-cholesterol, and blood pressure were not associated with worse nerve function; however, antihypertensive medication usage (suggestive of history of exposure to hypertension) was associated with worse peroneal compound muscle action potential amplitude and NCV. Smoking was associated with worse nerve function, higher VPT and higher risk for neuropathic pain. Inflammation was associated with worse nerve function and higher VPT, but only in those with type 2 diabetes. Type 2 diabetes and, to a lesser extent, prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were associated with worse nerve function, higher VPT and neuropathic pain (p for trend <0.01 for all outcomes).Conclusions/interpretationHyperglycaemia (including the non-diabetic range) was most consistently associated with early-stage nerve damage. Nonetheless, larger waist circumference, inflammation, history of hypertension and smoking may also independently contribute to worse nerve function.

Highlights

  • Diabetic neuropathy is one of the most common complications of diabetes mellitus [1], and a major cause of reduced quality of life, gait disturbances, foot ulceration, fall-related injuries and disability [2]

  • The same patterns were seen for vibration perception threshold (VPT) and neuropathic pain, except that older age and higher waist circumference were more strongly associated with a poorer VPT and there was no association of age and neuropathic pain

  • While type 2 diabetes was, as expected, clearly and consistently associated with worse nerve function and neuropathic pain, trend analyses showed that prediabetes appeared to be associated with worse nerve function and neuropathic pain

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Summary

Introduction

Diabetic neuropathy is one of the most common complications of diabetes mellitus [1], and a major cause of reduced quality of life, gait disturbances, foot ulceration, fall-related injuries and disability [2]. During their lifetimes, up to 50% of patients with type 2 diabetes are affected by some form of neuropathy, of which distal symmetric polyneuropathy is most common [3, 4]. The metabolic syndrome has been associated with neuropathy regardless of the presence of (pre)diabetes [13,14,15,16,17], but not consistently [7]

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