Background: Although pharmacotherapy with anticonvulsants and/or antidepressants can be effective for many people with painful diabetic neuropathy (PDN), albeit with frequent side-effects, a critical juncture occurs when neuropathic pain no longer responds to standard first- and second-step mono- and dual therapy and becomes refractory. Subsequent to these pharmacotherapeutic approaches, third-line treatment options for PDN may include opioids (short-term), capsaicin 8% patches, and spinal cord stimulation (SCS). Aim: This document summarizes consensus recommendations regarding appropriate treatment for refractory peripheral diabetic neuropathy (PDN), based on outcomes from an expert panel convened on December 10, 2022, as part of the Worldwide Initiative for Diabetes Education Virtual Global Summit, "Advances in the Management of Painful Diabetic Neuropathy." Participants: Nine attendees, eminent physicians and academics, comprising six diabetes specialists, two pain specialists, and one health services expert. Evidence: For individuals with refractory PDN, opioids are a high-risk option that do not provide a long-term solution and should not be used. For appropriately selected individuals, SCS is an effective, safe, and durable treatment option. In particular, high-frequency (HF) SCS (10 kHz) shows strong efficacy and improves quality of life. To ensure treatment success, strict screening criteria should be used to prioritize candidates for SCS. Consensus Process:: Each participant voiced their opinion after reviewing available data, and a verbal consensus was reached during the meeting. Conclusion: Globally, the use of opioids should rarely be recommended for refractory, severe PDN. Based on increasing clinical evidence, SCS, especially HF-SCS, should be considered as a treatment for PDN that is not responsive to first- or second-line monotherapy/dual therapy.

Background: While Diabetic Foot Ulcer (DFU) prevention and treatment have improved dramatically, assessment of DFU healing remains outdated, presenting a problem for research and clinical practice. Recent new mobile applications for standardizing DFU images have been reported, however, they are not automated and require large manual efforts. Aim: This study aims to define a reliable and sensitive metric by using machine learning to quantify wound severity, taking into account its size, shape, ischaemic and infection severity using a standard 2D photograph. This single metric could be used to identify and triage non-healing DFUs, as well as track wound healing in response to treatment. Method: Serial photographs of DFUs in 28 patients (90% T2DM, mean age 63, 83% male) with varying severity of DFU (72% UT 1A-C), were collected and analysed. Images from sequential clinic visits were automatically aligned. Wounds were automatically localized and segmented. Results: We have characterized DFUs and quantified changes in DFU characteristics across visits. 91% of baseline images were correctly identified and localized by the artificial intelligence (AI)-based wound localisation method. Discussion: If successful, this measure will facilitate targeting of appropriate therapies to individual patients, improving healing outcomes and therefore resulting in fewer amputations.

Aim Self-rated health, a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including persons with diabetes. This study examines correlates of self-rated health in adults with diabetic peripheral neuropathy (DPN). Methods Participants recruited from the UK and USA (n = 295; mean (+/- sd) age: 61.5 +/- 10.7 years; 69% male; 71% type 2 diabetes) rated their health at baseline and 18 months. DPN severity was assessed using the neuropathy disability score and the vibration perception threshold. Validated self-report measures assessed neuroticism, DPN-symptoms of pain, unsteadiness and reduced sensation in feet, DPN-related limitations in daily activities, DPN-specific emotional distress and symptoms of depression. Results In the fully adjusted baseline model, younger age, presence of cardiovascular disease and higher depression symptom scores showed likely clinically meaningful independent associations with worse health ratings. Being at the UK study site and presence of nephropathy indicated potentially meaningful independent associations with lower baseline health ratings. These predictors were largely consistent in their association with health ratings at 18 months. Conclusion Results identify independent correlates of health ratings among adults with DPN. Future research should investigate the clinical implications of associations and examine changes in these variables over time and potential effects on changes in health perceptions. If these associations reflect causal pathways, our results may guide interventions to target issues that are likely to have an impact on subjectively experienced health as an important patient-reported outcome in DPN care.

Novel plantar pressure-sensing smart insoles reduce foot ulcer incidence in ‘high-risk’ diabetic patients: a longitudinal study C.A. Abbott1, K.E. Chatwin1, A.N.B. Hasan1, S.M. Rajbhandari2, C. Sange2, N. Musa2, P. Foden3, K. Stocking3, L. Vileikyte4, F.L. Bowling4, A.J.M. Boulton4, N.D. Reeves1; 1Manchester Metropolitan University, Manchester, 2Lancashire Teaching Hospitals NHS Foundation Trust, Chorley, 3Wythenshawe Hospital, Manchester, UK, 4University of Manchester, Manchester, UK.

To the Editor: We read with interest the article by Vedhara and colleagues on coping, depression and healing of diabetic foot ulcers [1], as we believe the investigation of psychosocial aspects of foot ulceration is important and understudied. However, we were disappointed that claims of ‘influence’ and ‘mechanistic evidence’ in the title and conclusions of the paper do not appear to be supported by the data presented. Although problems regarding the reliability of depression and avoidance coping measures, and small sample sizes for secondary analyses are noted, other important methodological problems are not. First, the presented data provide no mechanistic evidence, but merely demonstrate that indicators of cortisol and matrix metalloproteinase (MMP) are associated with ulcer healing. It is not reported whether these potential mediators were associated with the predictors in question (i.e. depression and confrontational coping), or whether controlling for the purported mechanisms attenuated the relationship between the predictors and outcome [2]. As the authors had these data at their disposal, they could and ought to have evaluated the relationships between depression and coping, and cortisol and MMP, which they allude to in their discussion. Restricting their analyses to those with complete data on these variables would also have addressed the possibility that the reported differences in the associations between confrontational coping and depression, and ulcer healing and change in ulcer area may have been due to chance variations in the relationships between these variables across quite different samples (e.g. n=93 versus 21). It is also unclear why the authors stress a relationship between the pro-form of MMP2 and ulcer healing (the direction of which is misstated in the abstract). Wound fluid levels of the active form of this extracellular protease would be of functional significance, yet crucially no difference in active MMP2 levels was observed. Detailed histological analysis (e.g. in situ zymography) would have clarified this discrepancy. Importantly, depression was not associated with ulcer healing, but with change in ulcer area; the question of whether cortisol or MMP indices were related to change in ulcer area was not addressed. Thus, no data presented link these potential ‘mechanisms’ to depression or change in ulcer area. Second, the analytical approach could have affected important analyses. The authors note that there were no a priori hypotheses regarding which of three coping styles would be associated with their primary or secondary outcomes. There were also no predictions about which of five indicators of cortisol or four indices of MMP would be related to the two ulcer healing measures. Lack of hypotheses or control for familywise error may substantially increase the chance of spurious findings [3]. Over-fitting, or having too many predictor variables for a given sample J. S. Gonzalez (*) Ferkauf Graduate School of Psychology, Yeshiva University, Rousso Building, 1300 Morris Park Avenue, Bronx, NY 10461, USA e-mail: jeffrey.gonzalez@einstein.yu.edu

Diabet. Med. 28, 162–167 (2011) Abstract Aims To define and agree a practical educational framework for delivery by all healthcare professionals managing patients with diabetes, particularly those at low risk of developing foot complications. Methods A consensus meeting of a multidisciplinary expert panel. Prior to the meeting, relevant clinical papers were disseminated to the panel for review. The consensus was largely based upon the experts’ clinical experience and judgement. Results Four main health behaviours were identified for those at low risk of developing foot complications, namely:, control of blood glucose levels; attendance at annual foot screening examination; reporting of any changes in foot health immediately; and the engagement in a simple daily foot care routine. Conclusion There is currently little evidence‐based literature to support specific foot care practices. Patients with diabetes at low risk of developing complications should be encouraged to undertake a basic foot care regimen to reduce their likelihood of developing complications.

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co‐morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti‐depressants, the selective serotonin and noradrenaline re‐uptake inhibitors, anti‐convulsants, opiates, membrane stabilizers, the anti‐oxidant alpha‐lipoic acid and topical agents including capsaicin. Current first‐line therapies for painful DPN include tricyclic anti‐depressants, the serotonin and noradrenaline re‐uptake inhibitor duloxetine and the anti‐convulsants pregabalin and gabapentin. When prescribing any of these agents, other co‐morbidities and costs must be taken into account. Second‐line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone‐controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long‐term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non‐pharmacological approaches. Copyright © 2011 John Wiley & Sons, Ltd.

This study examined the relationship between symptoms of depression and the development of diabetic foot ulcers.

The aim of the study was to determine whether diabetic peripheral neuropathy (DPN) is a risk factor for depressive symptoms and examine the potential mechanisms for this relationship.