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INTRODUCTION: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN. OBJECTIVE: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN. METHODS: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process. RESULTS: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria. CONCLUSION: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.

Background and Aims Methods Results Conclusions The COVID‐19 pandemic significantly disrupted lower limb diabetes care. We aimed to map trends in diabetes‐related lower limb amputation and hospitalisation rates through the COVID‐19 pandemic.We performed a retrospective cohort study of all individuals who underwent a lower limb amputation for a diabetes‐related foot complication from 2018 to 2021 at the Royal Melbourne Hospital, a quaternary hospital in Australia. Hospitalisation rates with a diabetes‐related foot complication were collected for comparison. The start of the COVID‐19 epoch was defined as 16 March 2020, when a state of emergency was declared in Melbourne.During the study period, 360 lower limb amputations for diabetes‐related foot complications were performed in 247 individuals. The median monthly number of amputations remained stable prior to and during the COVID‐19 epoch; there was a median of 8.0 amputations per month (interquartile range (IQR) = 6.5–11) before COVID‐19, compared to 6.5 amputations (IQR = 5.0–8.3) during the COVID‐19 epoch (P = 0.23). Hospitalisation with a diabetes‐related foot complication significantly increased from a median monthly rate of 11 individuals (IQR = 9.0–14) before COVID‐19 to 19 individuals (IQR = 14–22) during the COVID‐19 epoch (p < 0.001).Despite increased hospitalisations for diabetes‐related foot complications during COVID‐19, there was not a corresponding increase in amputation rates. Face‐to‐face care of diabetes‐related foot complications was prioritised at this centre and may have contributed to stable amputation rates during the pandemic. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is highly prevalent among Jordanian patients, mostly are asymptomatic. Early recognition and appropriate management of neuropathy is important to improve symptoms, reduce sequelae, and improve quality of life. This study aims at exploring the role of pharmacists in the early recognition of DPN and providing quick screening for the presence of it among diabetic patients. A cross-sectional study was conducted at multi-pharmacy settings, in Irbid, Jordan. Twenty trained pharmacists who had bachelor's degrees in pharmacy participated in data collection. A total of 400 patients with confirmed diagnosis of type 2 diabetes mellitus (DM) according to the World Health Organization diagnostic criteria were recruited. DPN was assessed using the translated Arabic version of Michigan Neuropathy Screening Instrument (MNSI) history version. The mean MNSI questionnaire score for all participants was 4.40 ± 3.00. Mean age of the patients was 62.6 ± 10.7 years old and duration of diabetes was 8.25 ± 6.9. DN was present in 23.7% of the population. Diabetic patients with neuropathy were older than patients without neuropathy (p < 0.05) and had had diabetes longer (p < 0.05). Poor glycemic control, hypertension and gender, were significantly risk factors for DN (p < 0.05). In addition to delivering medications, this study suggests that pharmacists can have a role in screening and counseling about diabetic peripheral neuropathy using a simple objective, and non-invasive tool and also can determine level of damage and risk. [ABSTRACT FROM AUTHOR]

Context: Sweat glands (SGs) play a vital role in thermal regulation. The function and structure are altered during the different pathological conditions. Objective: These alterations are studied through three techniques: biopsy, sweat analytes and electrical activity of SG. Methods: The morphological study of SG through biopsy and various techniques involved in quantifying sweat analytes is focussed on here. Electrical activities of SG in diabetes, neuropathy and nephropathy cases are also discussed, highlighting their limitations and future scope. Results and Conclusion: The result of this review identified three areas of the knowledge gap. The first is wearable sensors to correlate pathological conditions. Secondly, there is no device to look for its structure and quantify its associated function. Finally, therapeutic applications of SG are explored, especially for renal failure. With these aspects, this paper provides information collection and correlates SG with pathologies related to diabetes. Hence this could help researchers develop suitable technologies for the gaps identified. [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) occurs in >50% of diabetic patients and is a high risk‐factor of balance problems and risk of falls. Impaired balance can lead to reduced function, which has a detrimental effect on patients' quality of life. Structured strength and balance training can result in sustained improvements in muscle strength, coordination, balance, functional status and quality of life. Objective: To determine the combined effects of strength and balance training versus aerobic training on balance, severity of symptoms of DPN, and quality of life in patients with DPN. Methods: This double blinded, two arm parallel design Randomized Clinical Trial. The study was conducted from March to December 2020 in the AIMS diabetic center Peshawar, Pakistan. Participants were selected through convenience sampling technique and randomly allocated into strength plus balance and aerobic training groups. Type 2 diabetic patients of both sexes, aged 40 to 80 years, with a Toronto neuropathy score ≥6 recruited, while patients with ulceration/infection of feet, medical/Surgical conditions, and non‐ambulatory patients were excluded from this study. Intervention was applied 3 days a week for 8 weeks. The Toronto clinical neuropathy system was used to assess neuropathy severity, SF‐36 to assess quality of life and the Berg balance scale was used for assessment of balance. Assessment was done at the baseline and after 8 weeks of intervention using SPSS. Version 22 was used for analysis. Results: The mean age of the participants was 60.80 ± 9.73. Between group analysis, which showed were statistically insignificant for neuropathy severity, balance and all domains of quality of life (p‐value >0.05) except SF‐36 General Health Perception Score, with Mean ± SD of 62.50 ± 7.54 in group A versus Mean ± SD of in group B 60.00 ± 15.98 (p‐value = 0.05). Within group analysis showed statistically significant results for neuropathy severity, balance and all domains of quality of life (p‐value<0.05). Conclusion: This study concluded that there is a statistically significant effect of structured balance and strength training and aerobic training on severity of DPN, balance and quality of life. But there was no statistically significant difference in improvement between the two intervention groups. [ABSTRACT FROM AUTHOR]

Persons with diabetic peripheral neuropathy (DPN) may face challenges such as balance issues due to reduced somatosensory feedback and an increased risk of developing diabetic foot ulcers (DFUs) due to increased plantar pressure. Pressure reducing footwear is thought to further impair balance. We introduced 3D-printed rocker midsoles and self-adjusting insoles that are able to reduce elevated plantar pressure values and aimed to prevent balance deterioration. However, their effect on the balance during walking (dynamic stability) is not analyzed yet. Is dynamic stability of persons with DPN impaired compared to healthy individuals and what is the effect of the 3D-printed rocker midsoles and self-adjusting insoles on the dynamic stability in this population? Dynamic stability, specifically the margins of stability (MOS) in the anterior-posterior (AP) and medio-lateral (ML) direction, was measured in ten healthy and nineteen persons with DPN. Independent-samples t-test was applied to analyze the difference in the MOS between groups. One-way repeated measures analyses of variance (ANOVA) was conducted to test the difference between the therapeutic footwear combinations within the DPN group. There is no significant difference between the healthy and DPN group in MOS-AP. MOS-ML is significantly larger in DPN compared to the healthy participants. Using the self-adjusting insole shows a significantly lower (negative) MOS-AP compared to when using a rocker shoe within the DPN group. This study provides valuable information on whether DPN and our therapeutic footwear have a negative effect on the dynamic stability. DPN does not have a negative effect on dynamic stability in the AP direction. For the ML direction, DPN seems to cause larger MOS-ML by likely using a compensation strategy (e.g., wider steps) while our experimental footwear does not further impair the MOS-ML. • DPN causes no change in anterior-posterior margins of stability (MOS-AP). • No negative effect of therapeutic footwear on MOS-AP. • No negative effect of therapeutic footwear on MOS in medio-lateral (ML) direction. • DPN causes larger MOS-ML as possible compensation strategy. [ABSTRACT FROM AUTHOR]

Background: The main objective of the study was to carry out a systematic literature review to investigate the beneficial role of antioxidants in obesity and diabetes and the association of antioxidants in neuro-gliopathies and gut microbiome on antioxidant production and enteric nervous system (ENS) protection. Methods: A literature search was done electronically on 8 June 2022 in the databases Google Scholar, and PubMed, reviewing all the articles published in English. There were no limitations for the study (region, or any time frame). The study included randomized controlled trials (RCTs) and observational studies on a human subject, primarily focusing on information such as a change in body weight, body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), fasting blood glucose level, glycated haemoglobin (HbA1c), and other parameters that connected with diabetes and obesity. The search was also conducted for neuro-gliopathies and gut microbiome. Results: The beginning database search picked out a total of 2,428 articles, 1,310 in PubMed, 876 in Google Scholar, and 242 records from other sources. A total of 2,040 (total duplicates 388) was found after removing the duplicated articles, and after reading the title and abstracts were further decreased to 139 full-text articles. These 139 studies went for full-text analysis, which resulted in the exclusion of 123 studies and generated a final 16 articles included for systemic analysis. Discussion: This literature search of present studies shows the interconnection between antioxidant intake among obese and diabetes neuro-gliopathies. The findings indicate both obese and diabetic patients have a minimum content of antioxidants, especially carotenoids, retinol, ascorbic acid, tocopherol, magnesium, and zinc. While few research illustrated that ingestion of the abovementioned antioxidants was lowered among diabetes and obese subjects in contrast with their normal-weight population, this was not endorsed by every study.

Dawood Sayed,1 Timothy Ray Deer,2 Jonathan M Hagedorn,3 Asim Sayed,4 Ryan S D’Souza,3 Christopher M Lam,1 Nasir Khatri,5 Zohra Hussaini,1 Scott G Pritzlaff,6 Newaj Mohammad Abdullah,7 Vinicius Tieppo Francio,1 Steven Michael Falowski,8 Yussr M Ibrahim,9 Mark N Malinowski,10 Ryan R Budwany,2 Natalie Holmes Strand,11 Kamil M Sochacki,12 Anuj Shah,13 Tyler M Dunn,11 Morad Nasseri,14 David W Lee,15 Leonardo Kapural,16 Marshall David Bedder,17,18 Erika A Petersen,19 Kasra Amirdelfan,20 Michael E Schatman,21,22 Jay Samuel Grider23 1Department of Anesthesiology and Pain Medicine, The University of Kansas Medical Center, Kansas City, KS, USA; 2Pain Services, Spine and Nerve Center of the Virginias, Charleston, WV, USA; 3Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 4Podiatry/Surgery, Susan B. Allen Memorial Hospital, El Dorado, KS, USA; 5Interventional Pain Medicine, Novant Spine Specialists, Charlotte, NC, USA; 6Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 7Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; 8Neurosurgery, Neurosurgical Associates of Lancaster, Lancaster, PA, USA; 9Pain Medicine, Northern Light Eastern Maine Medical Center, Bangor, ME, USA; 10OhioHealth Neurological Physicians, OhioHealth, Columbus, OH, USA; 11Anesthesiology and Pain Medicine, Mayo Clinic, Phoenix, AZ, USA; 12Department of Anesthesiology and Perioperative Medicine, Rutgers Robert Wood Johnson, New Brunswick, NJ, USA; 13Department of Physical Medicine and Rehabilitation, Detroit Medical Center, Detroit, MI, USA; 14Interventional Pain Medicine / Neurology, Boomerang Healthcare, Walnut Creek, CA, USA; 15Pain Management Specialist, Fullerton Orthopedic, Fullerton, CA, USA; 16Carolinas Pain Institute, Winston Salem, NC, USA; 17Chief of Pain Medicine Service, Augusta VAMC, Augusta, GA, USA; 18Associate Professor and Director, Addiction Medicine Fellowship Program, Department Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, USA; 19Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 20Director of Clinical Research, Boomerang Healthcare, Walnut Creek, CA, USA; 21Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 22Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 23Anesthesiology, Division of Pain Medicine, University of Kentucky College of Medicine, Lexington, KY, USACorrespondence: Dawood Sayed, Anesthesiology and Pain Medicine, the University of Kansas Medical Center, Kansas City, KS, USA, Tel +1 785-550-5800, Email dsayed@kumc.eduIntroduction: Painful diabetic neuropathy (PDN) is a leading cause of pain and disability globally with a lack of consensus on the appropriate treatment of those suffering from this condition. Recent advancements in both pharmacotherapy and interventional approaches have broadened the treatment options for PDN. There exists a need for a comprehensive guideline for the safe and effective treatment of patients suffering from PDN.Objective: The SWEET Guideline was developed to provide clinicians with the most comprehensive guideline for the safe and appropriate treatment of patients suffering from PDN.Methods: The American Society of Pain and Neuroscience (ASPN) identified an educational need for a comprehensive clinical guideline to provide evidence-based recommendations for PDN. A multidisciplinary group of international experts developed the SWEET guideline. The world literature in English was searched using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus to identify and compile the evidence for diabetic neuropathy pain treatments (per section as listed in the manuscript) for the treatment of pain. Manuscripts from 2000-present were included in the search process.Results: After a comprehensive review and analysis of the available evidence, the ASPN SWEET guideline was able to rate the literature and provide therapy grades for most available treatments for PDN utilizing the United States Preventive Services Task Force criteria.Conclusion: The ASPN SWEET Guideline represents the most comprehensive review of the available treatments for PDN and their appropriate and safe utilization.Keywords: diabetes, painful diabetic neuropathy, neuropathy, spinal cord stimulation, chronic pain, diabetic neuropathy

The exact mechanism by which diabetic neuropathy develops is still not fully known, despite our advances in medical knowledge. Progressing neuropathy may occur with a persistently favorable metabolic status in some patients with diabetes mellitus, while, in others, though seldom, a persistently unfavorable metabolic status is not associated with significant neuropathy. This might be significantly due to genetic differences. While recent years have brought compelling progress in the understanding of the pathogenetic background—in particular, accelerated progress is being made in understanding molecular biological mechanisms—some aspects are still not fully understood. A comparatively small amount of information is accessible on this matter; therefore, by summarizing the available data, in this review, we aim to provide a clearer picture of the current state of knowledge, identify gaps in the previous studies, and possibly suggest directions for future studies. This could help in developing more personalized approaches to the prevention and treatment of diabetic neuropathy, while also taking into account individual genetic profiles. [ABSTRACT FROM AUTHOR]

Neuropathy is a damage, disease, or dysfunction of one or more nerves especially of the peripheral nervous system. One of the most common disease causing neuropathy is diabetes mellitus. Diabetic neuropathy is a serious consequence that arises when nerve tissue is damaged by prolonged hyperglycemia. It affects a considerable portion of those who have the disease. This article covers every component of this complexed disease. We will discuss the definition, etiology, risk factors that patients can control and that are uncontrollable, and forms of neuropathies linked to diabetes such as peripheral, autonomic and focal. For more clinical approach signs and symptoms, diagnostic methods which are a mix of clinical evaluations, neurological exams, electrophysiological testing, and, in certain situations, imaging modalities and complicated nature of treating diabetic neuropathy will be explored. Moreover, challenges in treating this disease and future directions and research will be elaborated. What is more it interdisciplinary care will be explored as a key element in addressing complexed nature of diabetic neuropathy. In addition to highlighting the complexity of neuropathy in diabetes mellitus and emphasizing the vital significance of early recognition and specialized interventions for the best possible patient outcomes, the article aims to present a thorough grasp of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Purpose of Review: Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field. Recent Findings: This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. Summary: In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications. [ABSTRACT FROM AUTHOR]

Purpose: In this extensive review work, the important role of AMP-activated protein kinase (AMPK) in causing of diabetes mellitus has been highlighted. Structural feature of AMPK as well its regulations and roles are described nicely, and the association of AMPK with the diabetic complications like nephropathy, neuropathy and retinopathy are also explained along with the connection between AMPK and β-cell function, insulin resistivity, mTOR, protein metabolism, autophagy and mitophagy and effect on protein and lipid metabolism. Methods: Published journals were searched on the database like PubMed, Medline, Scopus and Web of Science by using keywords such as AMPK, diabetes mellitus, regulation of AMPK, complications of diabetes mellitus, autophagy, apoptosis etc. Result: After extensive review, it has been found that, kinase enzyme like AMPK is having vital role in management of type II diabetes mellitus. AMPK involve in enhance the concentration of glucose transporter like GLUT 1 and GLUT 4 which result in lowering of blood glucose level in influx of blood glucose into the cells; AMPK increases the insulin sensitivity and decreases the insulin resistance and further AMPK decreases the apoptosis of β-cells which result into secretion of insulin and AMPK is also involve in declining of oxidative stress, lipotoxicity and inflammation, owing to which organ damage due to diabetes mellitus can be lowered by activation of AMPK. Conclusion: As AMPK activation leads to overall control of diabetes mellitus, designing and developing of small molecules or peptide that can act as AMPK agonist will be highly beneficial for control or manage diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation. Methods: This review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database. Results: This review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM's full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM's impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance. Conclusion: Clinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted. [ABSTRACT FROM AUTHOR]

Diabetic painful neuropathy (DPN) is one of the most detrimental complications of diabetes. Alterations in neuroinflammatory mediators play significant roles in the development of DPN. Infiltration of the neutrophils and monocyte/macrophages contributes substantial role in the degenerative process of the distal sciatic nerve by forming neutrophil extracellular traps (NETs) under diabetic condition. Citrullination of histones due to increase in protein arginine deiminase (PAD) enzyme activity under hyperglycemia may promote NET formation, which can further increase the cytokine production by activating macrophages and proliferation of neutrophils. This study reveals that the increase in histone deacetylases (HDAC) is crucial in DPN and inhibition of HDAC using HDAC inhibitor (HDACi) FK228 would suppress NETosis and alleviate diabetic nerve degeneration and pain. FK228, also known as romidepsin, is FDA approved for the treatment of cutaneous T-cell lymphoma yet the molecular mechanisms of this drug are not completely understood in DPN. In this study, type 2 diabetic (T2D) mice with pain were treated with HDACi, FK228 1 mg/kg; I.P. 2 × /week for 3 weeks. The results demonstrate that FK228 treatment can alleviate thermal hyperalgesia and mechanical allodynia significantly along with changes in the expression of HDACs in the dorsal root ganglia (DRG) and spinal cord dorsal horn neurons of diabetic animals. The results also indicate that FK228 treatment can alter the expression of neutrophil elastase (NE), extracellular or cell free DNA (cfDNA), citrullinated histone-3 (CitH3), PADI4, growth-associated protein (GAP)-43, and glucose transporter (GLUT)-4. Overall, this study suggests that FK228 could amend the expression of nerve regeneration markers and inflammatory mediators in diabetic animals and may offer an alternative treatment approach for DPN. [ABSTRACT FROM AUTHOR]

The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending nociceptive drive due to amplification of, or a failure to suppress, incoming signals from the periphery. We aimed to explore whether a putative biomarker of spinal disinhibition, impaired rate-dependent depression of the Hoffmann reflex, is associated with a mechanistically appropriate and distinct pain phenotype in patients with painful diabetic neuropathy. In this cross-sectional study, 93 patients with diabetic neuropathy underwent testing of Hoffmann reflex rate-dependent depression and detailed clinical and sensory phenotyping, including quantitative sensory testing. Compared to neuropathic patients without pain, patients with painful diabetic neuropathy had impaired Hoffmann reflex rate-dependent depression at 1, 2 and 3 Hz (P ≤ 0.001). Patients with painful diabetic neuropathy exhibited an overall loss of function profile on quantitative sensory testing. However, within the painful diabetic neuropathy group, cluster analysis showed evidence of greater spinal disinhibition associated with greater mechanical pain sensitivity, relative heat hyperalgesia and higher ratings of spontaneous burning pain. These findings support spinal disinhibition as an important centrally mediated pain amplification mechanism in painful diabetic neuropathy. Furthermore, our analysis indicates an association between spinal disinhibition and a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive.

Abstract Background Peripheral neuropathy predisposes to diabetic foot and this predilection is worsened by poorly controlled sugars. Diabetic foot increases the mortality and morbidity associated with diabetes. Thus, it is crucial to screen for diabetic polyneuropathy. Early detection of diabetic polyneuropathy improves foot care and decreases morbidity. This study aimed to assess the sensitivity of Semmes Weinstein monofilament test in the diagnosis of Diabetic Peripheral Neuropathy. Forty-three Type 2 diabetes mellitus patients availing IP/OP services of a Medical College Hospital were included for the study. Patients underwent Semmes Weinstein monofilament test, following which they were subjected to nerve conduction study of both lower limbs. Results Forty six and half percentage of patients had diabetic peripheral neuropathy, taking NCS as gold standard.Of these 80% of the cases were also detected by the monofilament test.The specificity of the monofilament test was 100%. Positive predictive value was 100% and negative predictive value was 85.19% and the overall accuracy of the test was 90.7%. Conclusions In this study, we found that sensitivity and specificity of the SWM test are fairly high; thus, it can be used as a valid screening tool for DPN in resource limited settings, such as India.

Background: If unrecognized, Charcot neuro-osteoarthropathy (CNO) can be a devastating complication of diabetes. Methods: The aim of this retrospective study was to evaluate the outcomes in a cohort of diabetic patients diagnosed with active CNO managed in a tertiary level diabetic foot clinic (DFC). We included consecutive patients with active CNO, stage 0–1, according to the Eichenholtz–Shibata classification, who were referred from 1 January 2019 to 27 September 2022. Diagnosis of CNO was based on clinical signs and imaging (X-rays and magnetic resonance). All patients were completely offloaded by a total-contact cast (TCC) or removable knee-high device. Each patient was closely monitored monthly until CNO remission or another outcome. At 12 months of follow-up, the following outcomes were analyzed: remission, time to remission, major amputations (any above the ankle), and surgical indication. Results: Forty-three patients were included. The mean age was 57.6 ± 10.8 years; 65% were males and 88.4% had type 2 diabetes, with a mean duration of 20.6 ± 9.9 years. At baseline, 32.6% was affected by peripheral artery disease. Complete remission was recorded in 40/43 patients (93%), with a mean time to remission of 5.6 ± 1.5 months; major amputation and surgical indication occurred, respectively in 1/43 patients (2.3%) and 3/43 patients (7%). Conclusions: Early treatment of active Stage 0/1 CNO leads to high rates of remission and limb salvage. [ABSTRACT FROM AUTHOR]

Introduction: Autonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy. Methods: FINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (=12 points, n = 44; control <12 points, n = 28). HbA1c levels >5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model. Results: Mean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m² vs. 25.9 ± 8.9 kg/m²). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08-32.68; p < 0.041). Discussion: An increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic neuropathy can lead to decreased peripheral sensation and motor neuron dysfunction associated with impaired postural control and risk of falling. However, the relationship between decreased peripheral sensation and impaired vestibular function in diabetes mellitus is poorly investigated. Therefore, the aim of this study was to investigate the relationship between peripheral and autonomic measurements of diabetic neuropathy and measurements of vestibular function. Methods: A total of 114 participants with type 1 diabetes (n = 52), type 2 diabetes (n = 51) and controls (n = 11) were included. Vestibular function was evaluated by video head impulse testing. Peripheral neuropathy was assessed by quantitative sensory testing and nerve conduction. Autonomic neuropathy using the COMPASS 31 questionnaire. Data were analyzed according to data type and distribution. Results: Measurements of vestibular function did not differ between participants with type 1 diabetes, type 2 diabetes or controls (all p-values above 0.05). Subgrouping of participants according to the involvement of large-, small- or autonomic nerves did not change this outcome. Correlation analyses showed a significant difference between COMPASS 31 and right lateral gain value (ρ = 0.23, p = 0.02,), while no other significant correlations were found. Conclusion: Diabetic neuropathy does not appear to impair vestibular function in diabetes, by means of the VOR. Clinical trials: NCT05389566, May 25th, 2022. [ABSTRACT FROM AUTHOR]

Diabetic sensory-motor neuropathy (DSMN) is a prevalent complication of diabetes mellitus characterized by nerve damage leading to sensory deficits, motor dysfunction, and neuropathic pain. This abstract examines the clinical and diagnostic significance of the Systemic Immune Inflammation Index (SII) in DSMN. Recent research has highlighted the association between systemic inflammation and the pathogenesis of DSMN. The SII, calculated based on peripheral blood cell counts, serves as a composite marker reflecting the balance between systemic immune responses and inflammatory status. Clinical studies have demonstrated a positive correlation between elevated SII levels of DSMN. Patients with higher SII values exhibit more pronounced neuropathy symptoms and impaired nerve conduction velocities, indicating a potential link between inflammation-mediated processes and neuropathic damage. Furthermore, the SII has emerged as a valuable diagnostic tool for predicting DSMN related inflammatory sequel and monitoring disease progression. Its non-invasive nature and cost-effectiveness make it a promising biomarker for identifying individuals at risk of developing neuropathic complications in diabetes. This abstract underscores the clinical relevance of the SII in enhancing our understanding of the inflammatory mechanisms underlying DSMN and its potential utility in early detection and management strategies. Further investigation into the predictive value and therapeutic implications of the SII in DSMN is warranted to optimize patient care and outcomes. The present study aims to evaluate the potential role of SII in predicting inflammation in patients with Diabetic Sensory-motor Neuropathy. [ABSTRACT FROM AUTHOR]

Background: The assessment of the normative values of sensory nerve action potentials (SNAP) and their diagnostic accuracies using validated neuropathy‐assessment tools to classify participants into groups with and without neuropathy was not previously described in the literature. Methods: The Utah Early Neuropathy Scale (UENS), Michigan neuropathy‐screening instrument, and nerve conduction data were collected prospectively. We described and compared the values of the sural, superficial peroneal sensory (SPS), and superficial radial SNAP amplitude in different age groups for three groups. Group 1 (G1)—control participants (UENS <5), group 2 (G2)—participants with diabetes without clinical diabetic neuropathy (UENS <5), and group 3 (G3)—participants with clinical diabetic neuropathy (UENS ≥5). We also described the diagnostic accuracy of single‐nerve amplitude and a combined sensory polyneuropathy index (CSPNI) that consists of four total points (one point for each of the following nerves if their amplitude was <25% lower limit of normal: right sural, left sural, right SPS, and left SPS potentials). Results: We assessed 135 participants, including 41, 37, and 57 participants in G1, G2, and G3, respectively, with age median (interquartile ranges) of 51 (45–56), 47 (38–56), and 54 (51–61) years, respectively, whereas 19 (46.3%), 18 (48.7%), and 32 (56.14%) of them were males, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) scores were 68.4%, 92.3%, 86.7%, and 80% for the sural amplitude; 86%, 58.3%, 62%, and 84% for the SPS amplitude; 66.7%, 94.4%, 90.5%, and 78.2% for the CSPNI of 3; and 54.4%, 98.6%, 96.9%, and 73.2% for the CSPNI of 4, respectively. Conclusion: Sural nerve had a high specificity for neuropathy; however, the CSPNI had the highest specificity and PPV, whereas the SPS had the highest sensitivity and NPV. We described the sensitivity, specificity, positive predictive value, and negative predictive values of sensory nerve action potentials. We used a validated neuropathy scales to classify our participants into neuropathy and no neuropathy groups. These diagnostic accuracies were not reported in the previous literature. [ABSTRACT FROM AUTHOR]

Background: Peripheral neuropathy predisposes to diabetic foot and this predilection is worsened by poorly controlled sugars. Diabetic foot increases the mortality and morbidity associated with diabetes. Thus, it is crucial to screen for diabetic polyneuropathy. Early detection of diabetic polyneuropathy improves foot care and decreases morbidity. This study aimed to assess the sensitivity of Semmes Weinstein monofilament test in the diagnosis of Diabetic Peripheral Neuropathy. Forty-three Type 2 diabetes mellitus patients availing IP/OP services of a Medical College Hospital were included for the study. Patients underwent Semmes Weinstein monofilament test, following which they were subjected to nerve conduction study of both lower limbs. Results: Forty six and half percentage of patients had diabetic peripheral neuropathy, taking NCS as gold standard.Of these 80% of the cases were also detected by the monofilament test.The specificity of the monofilament test was 100%. Positive predictive value was 100% and negative predictive value was 85.19% and the overall accuracy of the test was 90.7%. Conclusions: In this study, we found that sensitivity and specificity of the SWM test are fairly high; thus, it can be used as a valid screening tool for DPN in resource limited settings, such as India. [ABSTRACT FROM AUTHOR]

N-arachidonoylethanolamine (also known as anandamide) and 2-arachidonoylglycerol are activators of the cannabinoid receptors. The endocannabinoid system also includes structurally and functionally related lipid mediators that do not target cannabinoid receptors, such as oleoylethanolamide, palmitoylethanolamide, and stearoylethanolamide. These bioactive lipids are involved in various physiological processes, including regulation of pain. The primary aim of the study was to analyze associations between serum levels of these lipids and pain in participants in the Pain in Neuropathy Study, an observational, cross-sectional, multicentre, research project in which diabetic patients with painless or painful neuropathy underwent deep phenotyping. Our hypothesis was that painful neuropathy would be associated with higher levels of the 5 lipids compared with painless neuropathy. Secondary aims were to analyze other patient-reported outcome measures and clinical data in relationship to lipid levels. The lipid mediators were analyzed in serum samples using liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum levels of anandamide were significantly higher in the painful group, but the effect size was small (Cohen d = 0.31). Using cluster analysis of lipid data, patients were dichotomized into a “high-level” endocannabinoid group and a “low-level” group. In the high-level group, 61% of patients had painful neuropathy, compared with 45% in the low-level group (P = 0.039). This work is of a correlative nature only, and the relevance of these findings to the search for analgesics targeting the endocannabinoid system needs to be determined in future studies. [ABSTRACT FROM AUTHOR]

Introduction: The increasing incidence of diabetes mellitus, especially in low-income countries, poses challenges to healthcare systems. Diabetic foot, a serious and preventable complication, results in high healthcare costs. Patient and family education, along with a structured care approach, reduces rates of ulceration, infection, and amputation in individuals with diabetes. This study evaluates the impact of diabetic foot on patients with diabetes mellitus from a Health Benefit Plan Administrator and proposes an educational model for its prevention. Methodology: Retrospective observational study analyzing patients with diabetes mellitus registered in a specific software, excluding those with other chronic diseases. Computer tools were used to identify cases of diabetic neuropathy, hospitalizations, and amputations due to diabetic foot, collecting data from 2020 and 2021 to analyze prevalence and incidence rates. A validated survey was designed to assess foot care in patients with diabetes mellitus. Results: These indicate a significant prevalence and incidence of diabetic foot complications in the studied patient cohort, with only 1.4% affected by diabetic neuropathy. An increase in the amputation rate was observed between 2020 and 2021 due to diabetic foot and its complications, accounting for 90% of hospitalizations among DM patients. The survey revealed symptoms related to diabetic foot in 70% of patients, emphasizing the need for early detection. The use of social marketing strategies is suggested to implement educational programs that reduce complications and improve the quality of life of patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background. Peripheral neuropathy is prevalent among patients with chronic kidney disease (CKD). Sudoscan non-invasively detects polyneuropathy by measuring electrochemical skin conductance (ESC). We conducted a study on sudomotor function in CKD patients across various stages based on their estimated glomerular filtration rate (eGFR). Methods. In this cross-sectional study of 700 CKD patients, all underwent Sudoscan. Pathological ESC was defined as hands < 40 μS or feet < 50 μS. Clinical neuropathy scores including Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique en 4 questionnaire (DN4) were obtained. Results. Among participants, 344 had diabetes and 356 did not. Hands and feet ESC decreased with CKD progression (median (IQR) in stage 1–2, 3, 4–5: 54.0 (39.0–68.0), 45.5 (30.0–63.0), 41.8 (26.5–60.5), p trend < 0.001; 64.5 (53.5–74.0), 60.5 (43.0–72.5), 55.0 (39.0–69.8), p trend < 0.001). Pathological hands and feet ESC increased in later CKD stages (stage 1–2, 3, 4–5: 26.6%, 40.9%, 45.7%, p trend < 0.001; 21.7%, 34.0%, 40.6%, p trend < 0.001). Positive hands and feet ESC-eGFR correlation existed irrespective of diabetes. Diabetic patients had lower hands and feet ESC than non-diabetics as CKD progressed. However, multivariate regression found no significant ESC-eGFR association. Sudoscan correlated with clinical neuropathy scores. Conclusion. Pathological sudomotor function was common in non-dialysis CKD stages 4–5. Diabetic patients had worse function. Sudomotor dysfunction progressed with renal disease but eGFR was not an independent risk factor. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), one of the most serious non-communicable diseases, has long-term negative effects on the healthcare system due to its microvascular and macrovascular manifestations, which can be fatal if left untreated. Nutraceuticals, on the other hand, are alternative therapy choices of orally consumed natural food ingredients applicable in the management of several diseases, including diabetes mellitus. Through their antioxidant capabilities and bioactive components, nutraceuticals have been clinically demonstrated to be effective in preventing a number of ailments, including cancer, diabetes, heart disease, and kidney problems. Flavonoids, which are categorized as phytochemicals, are present in several of these nutraceuticals. Cocoa, one of the flavanols engaged in the treatment of diabetes mellitus, provides an additional non-pharmaceutical intervention in the management of diabetes mellitus, which, in part, is because of its high antioxidant capacity. Additionally, flavonoids improve insulin resistance and sensitivity, dyslipidemia, endothelial function, and blood pressure, as well as lower oxidative stress and inflammatory processes. As a result, they may be able to stop the progression of long-term vascular consequences of diabetes, such as cardiovascular disease, neuropathy, nephropathy, and retinopathy. Therefore, the effects of nutraceuticals (as an alternative treatment) on diabetic-related micro- and macrovascular problems are the main focus of this review. [ABSTRACT FROM AUTHOR]

Copyright of Al-Anbar Journal of Veterinary Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Levodopa‐carbidopa intestinal gel therapy (LCIG), an effective treatment for advanced Parkinson's disease, can cause peripheral neuropathy. We present a 39‐year‐old man with LCIG‐related neuropathy with de novo diabetes mellitus (DM), decreased vitamin B6 and folate levels, and elevated homocysteine levels that developed over 2 years of LCIG treatment. Physicians should assess levels of levodopa metabolism‐associated vitamins and monitor risk factors of peripheral neuropathy, such as DM, before and after LCIG initiation. [ABSTRACT FROM AUTHOR]

Introduction: Distal polyneuropathy is a common complication of diabetes mellitus with a considerable negative impact on the quality of life. The aim of this study was to evaluate the effect of dry cupping on distal polyneuropathy in diabetic patients.Methods: This controlled clinical trial was performed on 34 patients with diabetic polyneuropathy (DPN) for eight weeks. The non-invasive dry and fixed cupping therapy was performed on the sole of the right foot in the patients three times a week for 10 min, and the left foot of the same patient was considered as a control. The severity of diabetic neuropathy was measured using the modified Toronto Clinical Neuropathy Score (mTCNS), and the symptom and sensory test scores were determined.Results: 20 patients (40 feet) completed the study. There was a significant difference between the control foot and the treated foot in terms of the mTCNS after four and eight weeks (p-values = 0.004 and 0.001, respectively), in terms of the sensory test scores after four and eight weeks (p-values = 0.007 and 0.005, respectively), and in terms of the symptom scores after eight weeks (p-value = 0.002).Conclusion: For the first time, this study demonstrated that cupping therapy might be effective as a complementary treatment in alleviating the symptoms of DPN, although understanding the underlying mechanism requires further investigation.

Objectives: Patients with ankle fractures associated with diabetes experience more complications following standard open reduction–internal fixation (ORIF) than those without diabetes. Augmented fixation strategies, namely extended ORIF and hindfoot nails (HFNs), may offer better results and early weightbearing in this group. The aim of this study was to define the population of patients with diabetes undergoing primary fixation for ankle fractures. Secondarily, we aimed to assess the utilisation of standard and augmented strategies and the effect of these choices on surgical outcomes, including early post-operative weightbearing and surgical complications. Methods: A national multicentre retrospective cohort study was conducted between January and June 2019 in 56 centres (10 major trauma centres and 46 trauma units) in the United Kingdom; 1360 patients with specifically defined complex ankle fractures were enrolled. The patients’ demographics, fixation choices and surgical and functional outcomes were recorded. Statistical analysis was performed to compare high-risk patients with and without diabetes. Results: There were 316 patients in the diabetes cohort with a mean age of 63.9 yrs (vs. 49.3 yrs. in the non-diabetes cohort), and a greater frailty score > 4 (24% vs. 14% (non-diabetes cohort) (p < 0.03)); 7.5% had documented neuropathy. In the diabetes cohort, 79.7% underwent standard ORIF, 7.1% extended ORIF and 10.2% an HFN, compared to 87.7%, 3.0% and 10.3% in the non-diabetes cohort. Surgical wound complications after standard-ORIF were higher in the diabetes cohort (15.1% vs. 8.7%) (p < 0.02), but patients with diabetes who underwent augmented techniques showed little difference in surgical outcomes/complications compared to non-diabetes patients, even though early-weightbearing rates were greater than for standard-ORIF. Conclusions: Ankle fractures in diabetes occur in older, frailer patients, whilst lower-than-expected neuropathy rates suggest a need for improved assessment. Augmented surgical techniques may allow earlier weightbearing without increasing complications, in keeping with modern guidelines in ankle fracture management.

Introduction: People with diabetic peripheral neuropathy (DPN) and limited joint mobility syndrome (LJMS) can experience increased forefoot peak plantar pressures (PPPs), a known risk factor for ulceration. The aim of this study was to investigate whether ankle and 1st metatarsophalangeal (MTP) joint mobilisations and home-based stretches in people with DPN improve joint range of motion (ROM) and reduce forefoot PPPs. Design and methods: Sixty-one people with DPN (IWGDF risk 2), were randomly assigned to a 6-week programme of ankle and 1st MTP joint mobilisations (n = 31) and home-based stretches or standard care only (n = 30). At baseline (T0); 6-week post intervention (T1) and at 3 months follow-up (T2), a blinded assessor recorded dynamic ankle dorsiflexion range using 3D (Codamotion) motion analysis and the weight bearing lunge test, static 1st MTP joint dorsiflexion ROM, dynamic plantar pressure and balance. Results: At T1 and T2 there was no difference between both groups in ankle dorsiflexion in stance phase, plantar pressure and balance. Compared to the control group, the intervention group showed a statistically significant increase in static ankle dorsiflexion range (Left 1.52 cm and 2.9cms, Right 1.62 cm and 2.7 cm) at 6 (T1) and 18 weeks (T2) respectively p < 0.01). Between group differences were also seen in left hallux dorsiflexion (2.75°, p < 0.05) at T1 and in right hallux dorsiflexion ROM (4.9°, p < 0.01) at T2 follow up. Further, functional reach showed a significant increase in the intervention group (T1 = 3.13 cm p < 0.05 and T2 = 3.9 cm p < 0.01). Intervention adherence was high (80%). Conclusions: Combining ankle and 1st MTP joint mobilisations with home-based stretches in a 6-week programme in people with DPN is effective in increasing static measures of range. This intervention may be useful for improving ankle, hallux joint mobility and anteroposterior stability limits in people with diabetes and neuropathy but not for reducing PPP or foot ulcer risk. Trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT03195855. [ABSTRACT FROM AUTHOR]

Zebrafish is now an excellent model in the world of research, with its genome making it a relevant subject of study for research into human diseases in order to understand cellular mechanisms. It is also easy to manipulate, small, transparent, and inexpensive. Nowadays, it is increasingly used to study diabetes and its complications at different levels of the body. In this way, in the present context, we are describing here some zebrafish-induced model of diabetes, focusing on the relevance of their associated neuropsychiatric manifestations, oxidative stress, gut microbiota, neuropathy and other relevant aspects. [ABSTRACT FROM AUTHOR]

Objective: Diabetic neuropathy is the most common chronic complication of diabetes mellitus. The vagal nerve and its branches might be affected, and the consequences can be very disastrous. This study aims to show if there is any subclinical vagal nerve involvement in diabetes mellitus. Methods: Fourteen patients with diabetic neuropathy without swallowing difficulty and dysphonia and 15 healthy controls were included in this prospective study. Nerve conduction studies, blink reflex, and swallowing studies were conducted. The results were compared between 2 groups. Results: Blink reflex exhibited abnormalities in patients compared to healthy controls. The recurrent laryngeal nerve motor response latency was significantly longer in patients (P < .001), whereas there was no significant difference for the pause period of swallowing. Conclusion: Prolonged distal motor latency of the recurrent laryngeal nerve in spite of normal swallowing pattern at the cricopharyngeal muscle electromyography in patients with diabetic neuropathy suggests subclinical vagal neuropathy and so lower cranial involvement. Patients should be informed about this clinical condition and closely followed up. [ABSTRACT FROM AUTHOR]

This document presents findings from a study on cardiovascular autonomic neuropathy (CAN) in patients with diabetes. The study aimed to identify risk factors for mortality in individuals with CAN. The results showed that older age at CAN diagnosis, decreased body mass index (BMI), and neurogenic orthostatic hypotension (NOH) were significant risk factors for mortality. Additionally, a genetic variant near the NR5A2 gene was associated with increased risk of CAN in non-Hispanic Caucasians. The study suggests that these findings could inform the development of guidelines for prevention and further research on CAN mortality risk factors. [Extracted from the article]

Background: Sudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (µS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting. Methods: In patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 µS and > 50 µS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 µS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland-Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices. Results: A total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [-5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®. Conclusion: The ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice. [ABSTRACT FROM AUTHOR]

Background: Diabetic amyotrophy, also known as diabetic proximal neuropathy, is a rare neuropathic complication of diabetes mellitus. It is most commonly characterized by severe pain in the hip and thigh, followed by asymmetric weakness and wasting of the proximal muscles of the lower limbs. Case Report: This paper presents the case of a 68-year-old man with an 8-month history of poorly controlled Type-2 diabetes mellitus who developed progressive asymmetrical weakness and atrophy in his left thigh. After a physical examination, magnetic resonance imaging, and electrophysiological studies, diabetic amyotrophy was diagnosed. Conclusion: Physicians should consider the possibility of diabetic amyotrophy in patients with diabetes mellitus who exhibit primary involvement of proximal muscles of the lower limbs, marked by pain, weakness, and atrophy. [ABSTRACT FROM AUTHOR]

Background: Worldwide, retinopathy, nephropathy, and neuropathy are the major diabetes-related microvascular complications. In Palestine, a low-middle-income country, diabetes is the fourth reason for death. However, a few studies examined diabetes microvascular consequences and its management. Therefore, we carried out a national study that aims to investigate the factors associated with diabetes-related microvascular complications among individuals seeking care in primary healthcare settings of the West Bank of Palestine. Method: Using a cluster systematic sampling technique, 882 participants with diabetes patients were chosen for a cross-sectional study from primary healthcare facilities operated by the Ministry of Health (PMoH), the United Nations Relief and Works Agency (UNRWA), and the Palestinian Medical Relief Society (PMRS). Data about patients related to diabetes-related complications, medication use, and other diseases were extracted from patients' medical records. In addition, an interview face-to-face questionnaire was used to collect information about patients' sociodemographic variables, medical history, smoking habits, duration of the disease, presence of concurrent conditions previous referrals, and hospital admissions, as well as their level of knowledge regarding diabetes, complications, and treatments. Results: Approximately 34.4% of persons with diabetes patients in Palestine encounter at least one microvascular complication associated with diabetes. The most prevalent diabetes-related microvascular complication was retinopathy (17.3%), 23.4% of participants had more than one microvascular complication, and 29% of male patients had erectile dysfunction. A higher probability of having any microvascular complications was associated with older age (over 60 years). Participants with diabetes patients with fundoscopy or ophthalmology reports, according to diabetes follow-up guidelines, were less likely to develop retinopathy. Also, those who performed regular kidney function testing were less likely to have nephropathy, and those who performed a regular foot exam were less likely to develop diabetic foot. Conclusions: Diabetes-related microvascular complications were associated with patient age, low education level, residency location, and adherence to diabetes follow-up guidelines of diabetes management; i.e., having been tested for HbA1c, consulting with specialists, regular kidney function, and foot examination. These factors can be utilized in setting up proper management protocols to prevent or delay microvascular complications in many patients. [ABSTRACT FROM AUTHOR]

To update the literature on the effectiveness of photobiomodulation (PBM) therapy in relieving pain in patients with diabetic peripheral neuropathy (DPN) compared to the effects of post-intervention, control/placebo groups, and other therapies. Search on the following databases: PORTAL PERIODICOS CAPES, PUBMED, GOOGLE ACADEMIC/SCHOLAR, SCOPUS, SCIELO, CENTRAL, and MEDLINE. Manual search: 1) manually capture the references of relevant articles originally selected to be included in the eligible studies. Two independent researchers performed the screening and selection of studies, methods assessment, and data extraction with unblinded authors and impressions. Subsequently, the full text of the originally selected studies was screened. The screening form registered the criteria for excluding literature from the full-text screening. The screening resulted in a total of 1692 citations. Out of these, 1402 citations were examined for titles and abstracts, followed by the removal of duplicated studies; therefore, 68 articles remained for full-text evaluation. 54 articles were excluded after full-text screening. Fourteen articles met the selection criteria, hence being selected and included in this narrative review. PBM showed to be a promising modality in relieving painful symptoms in DPN, especially when implemented in combination with other therapies, by improving the quality of life of diabetic patients. [ABSTRACT FROM AUTHOR]

Appropriate animal models, mimicking conditions of both health and disease, are needed to understand not only the biology and the physiology of neurons and other cells under normal conditions but also under stress conditions, like nerve injuries and neuropathy. In such conditions, understanding how genes and different factors are activated through the well-orchestrated programs in neurons and other related cells is crucial. Knowledge about key players associated with nerve regeneration intended for axonal outgrowth, migration of Schwann cells with respect to suitable substrates, invasion of macrophages, appropriate conditioning of extracellular matrix, activation of fibroblasts, formation of endothelial cells and blood vessels, and activation of other players in healthy and diabetic conditions is relevant. Appropriate physical and chemical attractions and repulsions are needed for an optimal and directed regeneration and are investigated in various nerve injury and repair/reconstruction models using healthy and diabetic rat models with relevant blood glucose levels. Understanding dynamic processes constantly occurring in neuropathies, like diabetic neuropathy, with concomitant degeneration and regeneration, requires advanced technology and bioinformatics for an integrated view of the behavior of different cell types based on genomics, transcriptomics, proteomics, and imaging at different visualization levels. Single-cell-transcriptional profile analysis of different cells may reveal any heterogeneity among key players in peripheral nerves in health and disease. [ABSTRACT FROM AUTHOR]

IntroductionDiabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation.MethodsThis review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database.ResultsThis review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM’s full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM’s impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance.ConclusionClinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted.

Abstract Background The assessment of the normative values of sensory nerve action potentials (SNAP) and their diagnostic accuracies using validated neuropathy‐assessment tools to classify participants into groups with and without neuropathy was not previously described in the literature. Methods The Utah Early Neuropathy Scale (UENS), Michigan neuropathy‐screening instrument, and nerve conduction data were collected prospectively. We described and compared the values of the sural, superficial peroneal sensory (SPS), and superficial radial SNAP amplitude in different age groups for three groups. Group 1 (G1)—control participants (UENS