Risk Factors of Sural Nerve Axonal Degeneration Using Clinically Relevant Thresholds in Context of Glucose Metabolism: The Maastricht Study

Introduction/Aims: To study the association of risk factors with axonal degeneration, based on below-threshold sural nerve amplitudes, as a proxy for distal symmetric polyneuropathy (DSP). In particular, to assess the differential contribution of risk factors in diabetes status subgroups. Methods: In 7242 participants of The Maastricht Study, a population-based cohort (aged 40 to 75 years, southern part of the Netherlands) focusing on type 2 diabetes (T2DM), associations between below-threshold sural nerve amplitudes (< 2.3 μV) and risk factors (diabetes status, demographics, anthropometrics, office systolic blood pressure, lifestyle, medication intake, and lipid profiles) were determined using logistic regression analysis in the total population and after stratification for no diabetes, prediabetes, and T2DM. Analyses were adjusted for age, sex, height, and body mass index (BMI). Results: Below-threshold sural nerve responses were observed in 741 participants (10.2%). Crude analysis showed increased odds of having below-threshold sural nerve responses for most factors; after adjustments, this association remained significant only for T2DM, female sex, older age, taller height, and a higher BMI. After stratification, individuals who were older, taller and had a higher BMI showed significantly increased odds of having below-threshold sural nerve responses in all subgroups. Notably, the increased odds for height and BMI were stronger in those with T2DM and prediabetes respectively. Higher odds for women were significant in the non-T2DM group only. Discussion: This study emphasizes the importance of preventive lifestyle measures targeting BMI in those with prediabetes, as other independent risk factors for axonal degeneration are nonmodifiable.