Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management

Abstract

Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in to 30–40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one third of painful DN patients derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc, which leads to the best therapeutic outcomes.

BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy

“…Quantitative sensory testing is a suitable tool to non-invasively assess and monitor sensory nerve function in response to controlled stimuli (small fibre function: cold, warmth, pain; large fibre function: vibration) 3 4. Temperature detection thresholds will be determined at the thenar eminence and dorsum of the foot (TSA-II NeuroSensory Analyzer, Medoc, Ramat Yishai, Israel), while vibration perception thresholds (VPTs) will be assessed at the second metacarpal bone and medial malleolus (Vibrameter, Somedic, Stockholm, Sweden).…”

“…DSPN is associated with considerable morbidity, increased mortality, foot ulcers and markedly impaired quality of life by causing neuropathic pain and sleep deprivation 2. Neuropathic symptoms include particularly pain, paraesthesia and numbness, while neuropathic signs comprise sensory deficits to touch, pressure, temperature and pain stimuli 2 3. However, DSPN frequently remains an underdiagnosed and undertreated condition as therapy options are limited 4…”

Ferrostatin-1 Attenuates Mechanical Hypersensitivity in Rats with Streptozotocin-Induced Diabetes by Inhibiting Spinal Ferroptosis

“…It has been reported that approximately one-third of individuals with DM are a icted with DNP over their disease course (Wang et al, 2014). Clinically, the predominant features of DNP include spontaneous pain, allodynia, and hyperalgesia (Jensen et al, 2021). More importantly, DNP has been well-regarded as a crucial risk factor that exerts an impact on the quality of life and life expectancy among DM patients (Selvarajah et al, 2019).…”

Molecular Aspects in the Potential of Vitamins and Supplements for Treating Diabetic Neuropathy

“…The pathogenesis is complex and multifactorial and includes immune-mediated, inflammatory, vascular, and metabolic pathways [2,3]. The clinical manifestations of classical diabetic symmetrical polyneuropathy (DSPN) include sensory and motor loss of the peripheral nerves to feet and hands, evident as a "stocking-and-glove" distribution mirroring a length-dependent axonopathy of the larger sensory and motor nerves in the extremities [4]. Thus, patients experience a number of paradoxical sensory deficits ranging from loss of protective sensation/numbness to debilitating neuropathic pain [5].…”