Diabetic neuropathy (DN) is a common complication of diabetes that is becoming an increasing concern as the prevalence of diabetes rapidly rises. There are several types of DN, but the most prevalent and studied type is distal symmetrical polyneuropathy, which is the focus of this review and is simply referred to as DN. It can lead to a wide range of sensorimotor and psychosocial symptoms and is a major risk factor for diabetic foot ulceration and Charcot neuropathic osteoarthropathy, which are associated with high rates of lower limb amputation and mortality. The prevention and management of DN are thus critical, and clinical guidelines recommend several strategies for these based on the best available evidence. This article aims to provide a narrative review of DN prevention and management strategies by discussing these guidelines and the evidence that supports them. First, the epidemiology and diverse clinical manifestations of DN are summarized. Then, prevention strategies such as glycemic control, lifestyle modifications and footcare are discussed, as well as the importance of early diagnosis. Finally, neuropathic pain management strategies and promising novel therapies under investigation such as neuromodulation devices and nutraceuticals are reviewed.

Distal symmetrical polyneuropathy (DSPN) is a serious complication of diabetes associated with significant disability and mortality. Although more than 50% of people with diabetes develop DSPN, its pathogenesis is still relatively unknown. This lack of understanding has limited the development of novel disease-modifying therapies and left the reasons for failed therapies uncertain, which is critical given that current management strategies often fail to achieve long-term efficacy. In this article, the pathogenesis of DSPN is reviewed, covering pathogenic changes in the peripheral nervous system, microvasculature and central nervous system (CNS). Furthermore, the successes and limitations of current therapies are discussed, and potential therapeutic targets are proposed. Recent findings on its pathogenesis have called the definition of DSPN into question and transformed the disease model, paving the way for new research prospects.

To assess a potential efficacy signal, safety and feasibility of neuromuscular electrical stimulation (NMES) therapy as an adjunct to standard care in patients with diabetic sensorimotor polyneuropathy (DSPN). In this single-centre, prospective, cohort, proof-of-concept study, 25 patients with DSPN consented to at least one daily 30-minute NMES therapy session (Revitive® IX) for 10 weeks, with 20 patients completing the study. The primary outcome measure was nerve conductivity assessed using a nerve conduction study of the sural, superficial peroneal, common peroneal and tibial nerves at 10 weeks compared to baseline. Secondary outcomes included superficial femoral artery (SFA) haemodynamics during NMES therapy compared to rest and quality-of-life at 10 weeks compared to baseline. At 10 weeks, there were significant increases in sural sensory nerve action potential amplitude and conduction velocity (p < 0.001), superficial peroneal sensory nerve action potential amplitude (p = 0.001) and conduction velocity (p = 0.002), common peroneal nerve conduction velocity (p = 0.004) and tibial nerve compound muscle action potential amplitude (p = 0.002) compared to baseline. SFA volume flow and time-averaged mean velocity significantly increased (p ≤ 0.003) during NMES compared to rest. Patient-reported Michigan Neuropathy Screening Instrument scores significantly decreased (p = 0.028) at 10 weeks compared to baseline. Three unrelated adverse events occurred, and 15 participants adhered to treatment. NMES therapy as an adjunct to standard care for 10 weeks significantly increased lower limb nerve conductivity in patients with DSPN and may be beneficial in the treatment of DSPN.

Therapeutic options for people experiencing neuropathic pain from diabetic peripheral neuropathy are limited, and impact can be severe. Physical and psychological interventions remain under-explored but may offer promise, especially in multimodal combination programs. To address this gap, an intervention was developed according to the Medical Research Council's framework for complex interventions, including research expert and stakeholder input. This will be tested for acceptability and feasibility in a trial. NeuOst (Neuropathy Optimisation through Self-management and Therapy) is a manual therapy-based intervention, incorporating exercise, psychologically informed training, and education. The protocol for a single-site, parallel, three-arm, partially participant-blinded, randomized controlled trial is presented. The experimental treatment is a 5-week course of NeuOst as adjunct to patients' usual care. Comparators are a control intervention that lacks pre-specified components of interest as adjunct to usual care and usual care only in adults with painful diabetic peripheral neuropathy. The follow-up period is 16 weeks. Primary outcomes are feasibility measures such as recruitment, eligibility, and consent rates, retention, blinding, fidelity, acceptability, and safety. Secondary and exploratory outcomes involve clinical measures and qualitative feedback. A protocol was prospectively registered (NCT06423391). After initial intervention development, a feasibility trial will inform intervention refinement and future research steps. www.clinicaltrials.gov identifier is NCT06423391.

Aims: Diabetic sensorimotor polyneuropathy (DSPN) is the most common chronic complication of diabetes. Heterogeneity in outcome measures across DSPN trials may have hindered the development of novel therapies. No core outcome set (COS) exists to standardise DSPN trial outcomes. This systematic review aims to identify and synthesise outcomes reported in DSPN interventional trials. Methods: The protocol was pre‐registered on PROSPERO (CRD42023408403) and reported in line with Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Prospective DSPN interventional trials since 2018 were searched with a predefined strategy, and primary and secondary verbatim outcomes were extracted, merged and organised using a taxonomy recommended by Core Outcome Measures in Effectiveness Trials (COMET). Outcome measuring tools were summarised descriptively. Results: Of the 4851 abstracts screened, 184 were eligible (protocols, n = 24; ongoing trials, n = 48 completed trials without published results, n = 11; published trials with results, n = 101). Pain was the most common primary ( n = 127) and secondary ( n = 64) unique outcome. By taxonomy, nervous system outcomes were the most common primary ( n = 174) and secondary ( n = 89) measure. The most common measuring tools were the visual analogue scale ( n = 37), numerical rating scale ( n = 37) and nerve conduction study ( n = 34). Over 30 distinct measuring tools were utilised to measure nervous system outcomes. Conclusions: Despite consistent outcome reporting, variability in measuring tools highlights the need for a COS with standardised tools. Patient‐reported outcomes were more common than assessor‐reported outcomes; however, using both may reduce response variability and bias. These findings will inform a future Delphi process to develop a COS for DSPN.