Higher disease burden and greater small fibre impairment in women with painful diabetic neuropathy

Objective: Although the incidence of Painful-Diabetic Peripheral Neuropathy (Painful-DPN) is higher in women, the underlying reasons for this are not known. This study investigated sex differences in pain and neurological phenotypes in 2 cohorts of patients with Painful-DPN. Methods: Two cohort analyses were performed in this retrospective analysis of participants with Painful-DPN recruited to cross-sectional studies: (1) Patient-Reported Outcomes Measures Cohort analysis (n = 184), which assessed neuropathic pain intensity (Numeric Rating Score), neuropathic symptoms (Neuropathic Pain Scale), mood (Hospital Anxiety and Depression Scale), quality of life (Norfolk QoL-DN), and sleep (Medical Outcomes Sleep Study); (2) Neurological Phenotyping Cohort analysis (n = 100), which assessed large- (Neuropathy Impairment Score of the Lower Limb plus Seven Neurophysiological Tests) and small-nerve fibre function. Participants were also divided into irritable (IR) and nonirritable nociceptor phenotypes. Results: In the first cohort analysis, women reported greater neuropathic pain symptom burden, poorer sleep, and higher anxiety prevalence than men. In the second cohort analysis, men had greater large-nerve fibre impairment, whereas women exhibited more severe small-fibre dysfunction. In addition, IR nociceptor phenotypes were more prevalent in women. Conclusion: Women with Painful-DPN experience a greater disease burden, increased small-fibre impairment, and are more likely to have the IR nociceptor phenotype, suggesting potential sex-specific disease mechanisms.