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The term »the diabetic hand« traditionally denotes complications affecting the hand in individuals with diabetes mellitus, such as restricted finger movement, numbness, and pain. Trigger finger, Dupuytren's disease, carpal tunnel syndrome, ulnar nerve entrapment, and osteoarthritis of the first carpometacarpal joint are all conditions that are more prevalent among individuals with both type 1 and type 2 diabetes. This overview aims to shed light on a somewhat neglected area in diabetes complications, i.e. the diabetic hand, to increase the knowledge among physicians and surgeons as well as nurses, physiotherapists, and occupational therapists treating patients with diabetes.

Objective: To evaluate the effect of nerve decompression on pain in patients with lower extremity painful diabetic peripheral neuropathy (DPN)., Background: Currently, no treatment provides lasting relief for patients with DPN. The benefits of nerve decompression remain inconclusive., Methods: This double-blinded, observation and same-patient sham surgery-controlled randomized trial enrolled patients aged 18 to 80 years with lower extremity painful DPN who failed 1 year of medical treatment. Patients were randomized to nerve decompression or observation group (2:1). Decompression-group patients were further randomized and blinded to nerve decompression in either the right or left leg and sham surgery in the opposite leg. Pain (11-point Likert score) was compared between decompression and observation groups and between decompressed versus sham legs at 12 and 56 months., Results: Of 2987 screened patients, 78 were randomized. At 12 months, compared with controls (n=37), both the right-decompression group (n=22) and left-decompression group (n=18) reported lower pain (mean difference for both: -4.46; 95% CI: -6.34 to -2.58 and -6.48 to -2.45, respectively; P < 0.0001). Decompressed and sham legs equally improved. At 56 months, compared with controls (n=m 14), pain was lower in both the right-decompression group (n=20; mean difference: -7.65; 95% CI: -9.87 to -5.44; P < 0.0001) and left-decompression group (n=16; mean difference: -7.26; 95% CI: -9.60 to -4.91; P < 0.0001). The mean pain score was lower in decompressed versus sham legs (mean difference: 1.57 95% CI: 0.46 to 2.67; P =0.0002)., Conclusions: Although nerve decompression was associated with reduced pain, the benefit of surgical decompression needs further investigation as a placebo effect may be responsible for part or all of these effects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Diabetic neuropathy is a frequent and severe degenerative complication of diabetes. The diagnosis is easily performed in painful symptomatic patients. Sensitivity disorders responsible for numbness, tingling, and loss of feeling are part and parcel of diabetic foot syndrome and require investigation in view of preventing trophic ulcers. To date, there exists no specific treatment for diabetic neuropathy possibly preventable by careful control of metabolic disorder. Effective management of diabetic patients would make it possible to limit the dramatic consequences of diabetic neuropathy while at the same time acting on other complications., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to report for this text., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN)., Research Design and Methods: This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes., Results: During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses., Conclusions: Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients., (© 2024 by the American Diabetes Association.)

Abstract: Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes. Painful diabetic neuropathy is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, axonal degeneration, and changes in cutaneous innervation. However, the complete molecular profile underlying the hyperexcitable cellular phenotype of DRG nociceptors in PDN has not been elucidated. This gap in our knowledge is a critical barrier to developing effective, mechanism-based, and disease-modifying therapeutic approaches that are urgently needed to relieve the symptoms of PDN. Using single-cell RNA sequencing of DRGs, we demonstrated an increased expression of the Mas-related G protein-coupled receptor d (Mrgprd) in a subpopulation of DRG neurons in the well-established high-fat diet (HFD) mouse model of PDN. Importantly, limiting Mrgprd signaling reversed mechanical allodynia in the HFD mouse model of PDN. Furthermore, in vivo calcium imaging allowed us to demonstrate that activation of Mrgprd-positive cutaneous afferents that persist in diabetic mice skin resulted in an increased intracellular calcium influx into DRG nociceptors that we assess in vivo as a readout of nociceptors hyperexcitability. Taken together, our data highlight a key role of Mrgprd-mediated DRG neuron excitability in the generation and maintenance of neuropathic pain in a mouse model of PDN. Hence, we propose Mrgprd as a promising and accessible target for developing effective therapeutics currently unavailable for treating neuropathic pain in PDN., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Introduction: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality., Research Design and Methods: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment., Results: The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events., Conclusions: While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes., Competing Interests: Competing interests: TWH owns shares in Novo Nordisk. NT and SAW are full-time employees of and own shares in Novo Nordisk. CL-Q has served on advisory panels and/or received research support from Pfizer, Novo Nordisk and other companies via the IMI funding scheme. PR has received consultancy and/or speaking fees (to his institution) from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Vifor, and Sanofi Aventis, and holds research grants from AstraZeneca and Novo Nordisk., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies., Objective: The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM., Methods: A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies., Results: A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM., Conclusion: Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dilixiati, Waili, Tuerxunmaimaiti, Tao, Zebibula and Rexiati.)

Preclinical studies indicate that diverse muscarinic receptor antagonists, acting via the M 1 sub-type, promote neuritogenesis from sensory neurons in vitro and prevent and/or reverse both structural and functional indices of neuropathy in rodent models of diabetes. We sought to translate this as a potential therapeutic approach against structural and functional indices of diabetic neuropathy using oxybutynin, a muscarinic antagonist approved for clinical use against overactive bladder. Studies were performed using sensory neurons maintained in vitro, rodent models of type 1 or type 2 diabetes and human subjects with type 2 diabetes and confirmed neuropathy. Oxybutynin promoted significant neurite outgrowth in sensory neuron cultures derived from adult normal rats and STZ-diabetic mice, with maximal efficacy in the 1-100 nmol/l range. This was accompanied by a significantly enhanced mitochondrial energetic profile as reflected by increased basal and maximal respiration and spare respiratory capacity. Systemic (3-10 mg/kg/day s.c.) and topical (3% gel daily) oxybutynin reversed paw heat hypoalgesia in the STZ and db/db mouse models of diabetes and reversed paw tactile allodynia in STZ-diabetic rats. Loss of nerve profiles in the skin and cornea of db/db mice was also prevented by daily topical delivery of 3% oxybutynin for 8 weeks. A randomized, double-blind, placebo-controlled interventional trial was performed in subjects with type 2 diabetes and established peripheral neuropathy. Subjects received daily topical treatment with 3% oxybutynin gel or placebo for 6 months. The a priori designated primary endpoint, significant change in intra-epidermal nerve fibre density (IENFD) in skin biopsies taken before and after 20 weeks of treatments, was met by oxybutynin but not placebo. Secondary endpoints showing significant improvement with oxybutynin treatment included scores on clinical neuropathy, pain and quality of life scales. This proof-of-concept study indicates that muscarinic antagonists suitable for long-term use may offer a novel therapeutic opportunity for treatment of diabetic neuropathy. Trial registry number: NCT03050827., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: People with diabetic peripheral neuropathy (DPN) report fluctuating foot symptoms. This study used ecological momentary assessment to: (1) compare foot symptoms between days, time points and periods with/without preceding physical activity or pain medication; and (2) determine relationships between symptoms and endogenous pain modulation., Method: Ten low-active Australian adults with probable DPN underwent temporal summation of pain (TSP) and conditioned pain modulation (CPM) then completed mobile phone surveys five times daily for seven days, where they recorded the intensity of six foot symptoms and whether they performed physical activity or consumed pain medication in the preceding three hours.  RESULTS: All foot symptoms except numbness were greater in periods following physical activity, whereas periods following pain medication showed greater shooting pain. TSP showed very large correlations with sensitivity to touch, burning pain, shooting pain and prickling/tingling.  DISCUSSION: General practitioners should be aware that physical activity might exacerbate symptoms of DPN when encouraging their patients to be active.

Context: Macrovascular outcomes in type 2 diabetes have improved over recent decades. There are scant equivalent distal symmetric polyneuropathy (DSPN) data., Objective: This work aimed to characterize temporal changes in DSPN prevalence and incidence rates (IRs) in community-based Australians., Methods: An observational study was conducted among an urban population. Participants included individuals with type 2 diabetes from the Fremantle Diabetes Study phases I (FDS1; n = 1296 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011). Main outcome measures included Michigan Neuropathy Screening Instrument (MNSI) clinical grading., Results: DSPN prevalence by 8-point MNSI was 30.8% (FDS1) and 58.9% (FDS2; P < .001), and by 6-point (excluding foot appearance) and 2-point (biothesiometry alone) MNSI was 37.5% and 35.7% (P = .336), and 33.8% and 38.7% (P = .011), respectively. Given between-phase changes in appearance assessment, 8-point MNSI data were not analyzed further. In multivariable analysis, FDS2 vs FDS1 participation was associated with 6-point (odds ratio (95% CI) 0.68 (0.56-0.83); P < .001) but not 2-point (0.90 (0.74-1.11); P = .326) MNSI DSPN prevalence. Four-year DSPN IRs (95% CI) for 6-point MNSI were 13.6 (12.0-15.4) and 17.6 (15.9-19.4)/100 person-years in FDS1 and FDS2, respectively (IR ratio [IRR] 1.31 [1.12-1.55]; P < .001), and for 2-point MNSI were 13.9 (12.3-15.8) and 7.4 (16.3-8.6/100 person-years; IRR 0.53 [0.43-0.64]; P < .001). FDS2 vs FDS1 independently predicted incident DSPN for 6-point (hazard ratio [95% CI] 1.25 [1.06-1.48]; P = .009) and 2-point (0.42 [0.33-0.55]; P < .001) MNSI., Conclusion: DSPN prevalence was lower or equivalent in FDS2 vs FDS1, and its incidence was greater or lower, in multivariable models depending on the MNSI features used., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Diabetes is a global health problem causing a significant burden on the healthcare systems both due to the disease itself and associated complications. Diabetic radiculoplexus neuropathies or Bruns-Garland syndrome constitutes a rare form of microvascular complications, more commonly affecting the lumbosacral plexus and, very rarely, the cervical plexus. We describe two Sri Lankan males who presented with diabetic lumbosacral radiculoplexus neuropathy and diabetic cervical radiculoplexus neuropathy as the initial manifestation of diabetes., Case Description: Case 1: a 49-year-old Sri Lankan hotel chef presented with subacute painful weakness and wasting of the left upper arm for 3 months and weight loss. Left upper limb proximal muscles were wasted with diminished power and reflexes. A nerve conduction study showed comparative amplitude reduction. An electromyogram revealed positive sharp waves, frequent fibrillations, and high amplitude polyphasic motor unit potentials with reduced recruitment in proximal muscles of left upper limb. Case-2: a 47-year-old Sri Lankan carpenter presented with subacute progressive asymmetrical painful weakness and wasting of bilateral thighs for 5 months and weight loss. Lower limb proximal muscles were wasted with reduced power and knee jerks. The nerve conduction study was normal. The electromyogram was similar to case 1 involving both quadratus femoris muscles, which was more prominent on the left side. The work up for an underlying etiology revealed only elevated fasting blood glucose and HbA1c, suggesting a new diagnosis of diabetes associated with neurological symptoms. Patient 1 was diagnosed with diabetic cervical radiculoplexus neuropathy and patient 2 with diabetic lumbosacral radiculoplexus neuropathy. Both showed significant improvement following optimization of glycemic control together with symptomatic treatment and physiotherapy., Conclusion: Diagnosis of diabetic radiculoplexus neuropathy requires a comprehensive workup to rule out other sinister pathologies. This case report has a dual importance; it describes diabetic radiculoplexus neuropathy as the very first manifestation of two previously healthy people, giving rise to a new diagnosis of diabetes and, at the same time, reporting on diabetic cervical radiculoplexus neuropathy, which is extremely rare and has never been previously reported in Sri Lanka., (© 2024. The Author(s).)

Diabetic peripheral neuropathy is the most prominent microvascular complication of diabetes mellitus and the leading cause of ulceration, amputation, and extended hospitalization. Evidence regarding the magnitude and factors associated with diabetic peripheral neuropathy is not well documented in Ethiopia, particularly in the study area. A facility-based cross-sectional study was conducted among 293 adult type 2 diabetic patients who were on treatment and follow-up from May to June 31, 2023. To select participants in the study, a systematic random sampling method was utilized. Data were collected using semi-structured questionnaires and medical record reviews. The Michigan Neuropathy Screening Instrument (MNSI) was employed to assess diabetic peripheral neuropathy. To model the association between diabetic peripheral neuropathy and independent variables, binary logistic regression model was used. An adjusted odds ratio with a 95% confidence interval was used to estimate the association and statistical significance was proclaimed at a p-value < 0.05. The magnitude of diabetic peripheral neuropathy was 14.3% (95% CI 10.4-18.0). It was 13.4% (95% CI 8.4-19.1) among males and 15.4% (95% CI 10.1-22.2) among females. Age above 60 years (AOR = 5.06, 95% CI 1.60-15.96), being rural resident (AOR = 2.41; 95% CI 1.15-5.06), duration of diabetes above 5 years (AOR = 2.48, 95% CI 1.16-5.27) and having comorbid hypertension (AOR = 2.56, 95% CI 1.24-5.28) were independently associated with diabetic peripheral neuropathy. One in seven adult type 2 diabetes patients in the study area had diabetic peripheral neuropathy. Factors such as age, place of residence, duration of diabetes, and comorbid hypertension showed positive associations with diabetic peripheral neuropathy. Thus, it is imperative to give special consideration to diabetic patients who are elderly, living in rural areas, experiencing a prolonged duration of diabetes, or dealing with comorbid hypertension., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

Introduction: Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades., Methods: The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized., Results: The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise., Conclusions: The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM-SVM-RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co-upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co-upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory-oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM-RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Diabetic complications, especially diabetic retinopathy, diabetic nephropathy and painful diabetic neuropathy, account for a large portion of patients with diabetes and display rising global prevalence. They are the leading causes of blindness, kidney failure and hypersensitivity to pain caused by diabetes. Current approved therapeutics against the diabetic complications are few and exhibit limited efficacy. The enhanced cell-specificity, stability, biocompatibility, and loading capacity of drugs are essential for the mitigation of diabetic complications. In the article, we have critically discussed the recent studies over the past two years in material sciences and biochemistry. The insightful concepts in these studies drive the development of novel nanoparticles and mesenchymal stem cells-derived extracellular vesicles to meet the need for treatment of diabetic complications. Their underlying biochemical principles, advantages and limitations have been in-depth analyzed. The nanoparticles discussed in the article include double-headed nanodelivery system, nanozyme, ESC-HCM-B system, soft polymer nanostars, tetrahedral DNA nanostructures and hydrogels. They ameliorate the diabetic complication through attenuation of inflammation, apoptosis and restoration of metabolic homeostasis. Moreover, mesenchymal stem cell-derived extracellular vesicles efficiently deliver therapeutic proteins to the retinal cells to suppress the angiogenesis, inflammation, apoptosis and oxidative stress to reverse diabetic retinopathy. Collectively, we provide a critical discussion on the concept, mechanism and therapeutic applicability of new delivery tools to treat these three devastating diabetic complications., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Background: Patients suffering from polyneuropathy often complain of pain, tingling, and numbness sensations, as well as an increased risk of falling with the corresponding subsequent complications. If symptoms persist after conservative treatment options have been exhausted, nerve decompression in the lower extremity, as described by Dellon, can bring about an improvement in symptoms in many patients. Dellon originally reported that this surgery led to very successful outcomes in patients with diabetic polyneuropathy. In this study, we compare our postsurgical results in patients with diabetic versus idiopathic polyneuropathy., Methods: Thirty-three patients with idiopathic or diabetic polyneuropathy who had undergone Dellon nerve decompression in the lower extremity between 2011 and 2013 were included in the retrospective study. Pain (numeric rating scale [NRS] 0-10; 0, no pain; 10, worst imaginable pain), tingling, numbness, Hoffmann-Tinel sign, and Semes-Weinstein monofilament were assessed in 20 patients with diabetic polyneuropathy and in 13 patients with idiopathic polyneuropathy., Results: Three months after surgery, a significant reduction in pain was evident in patients with diabetic polyneuropathy, from a preoperative level of NRS 4.9 (minimum, 0; maximum, 10) to 2 (minimum, 0; maximum, 8; P = 0.005). Ninety percent of patients complained of tingling ( P = 0.000) before surgery and 18% after surgery, whereas 100% complained of numbness before surgery and 41% ( P = 0.000) after surgery. One hundred percent of patients had no measurable surface sensitivity before surgery (measured with the Semes-Weinstein monofilament), whereas 3 months after surgery, only 24% of patients still had no measurable surface sensitivity ( P = 0.000). A positive Hoffmann-Tinel sign was recorded in 85% of patients before surgery and only in 11% 3 months after surgery ( P = 0.000). In the case of patients with idiopathic polyneuropathy, a reduction in pain was evident 3 months after surgery, from a preoperative level of NRS 3.9 (minimum, 0; maximum, 9) to 2.2 (minimum, 0; maximum, 9; P = 0.058). Seventy-seven percent of patients complained of tingling before surgery and 42% after surgery ( P = 0.111), whereas 92% complained of numbness before surgery and 50% after surgery ( P = 0.030). Seventy-seven percent of patients had no measurable surface sensitivity before surgery (measured with the Semes-Weinstein monofilament), whereas 3 months after surgery, only 33% of patients still had no measurable surface sensitivity ( P = 0.047). A positive Hoffmann-Tinel sign was recorded in 62% of patients before surgery and only in 17% 3 months after surgery ( P = 0.041)., Conclusions: Not only patients with diabetic polyneuropathy but also those with idiopathic polyneuropathy benefit from Dellon nerve decompression surgery in the lower extremities., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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/m 2 vs. 25.9 ± 8.9 kg/m 2 ). 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Körei, Békeffy, Menyhárt, Osgyán, Istenes, Horváth and Kempler.)

Background: This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting., Methods: This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h)., Results: Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation., Conclusion: DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy., (© 2024. The Author(s).)

A majority of older patients suffer from neuropathic pain (NP) that significantly alters their daily activities and imposes a significant burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it challenging to determine the appropriate drug, dosage, and maintenance of therapy. Age-dependent processes play a contributing role in neuropathy given that diabetic neuropathy (DN) is the most common form of neuropathy. This narrative review is mainly focused on the drug treatment approach for neuropathy-associated pain in aged people including both drugs and dietary supplements, considering the latter as add-on mechanism-based treatments to increase the effectiveness of usual treatments by implementing their activity or activating other analgesic pathways. On one hand, the limited clinical studies assessing the effectiveness and the adverse effects of existing pain management options in this age segment of the population (> 65), on the other hand, the expanding global demographics of the elderly contribute to building up an unresolved pain management problem that needs the attention of healthcare providers, researchers, and health authorities as well as the expansion of the current therapeutic options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetic Peripheral Neuropathy (DPN) causes various physical problems such as the increased risk of falling, loss of balance and coordination while standing or walking, susceptibility to injuries due to sensory loss., Aims: The aim of the study was to evaluate and compare the effects of neuropathic pain (NP) in individuals with DPN on balance and gait., Methods: This prospective controlled study was conducted on 42 adults aged between 40-65 years. The participants were divided into three groups; individuals with DPN and NP (DPN+NP/n = 14), individuals with DPN without NP (DPN-NP/n = 14), and the control group ( n  = 14), respectively. The Force Plate system and Core Balance System measured static and dynamic postural balance and stability limits. Gait and dynamic plantar pressure distribution analyses were performed with a computerized gait evaluation system., Results: The score of LANSS, and VAS during gait were higher in DPN+NP group than in DPN-NP ( p  < 0.05). No significant difference was observed between the groups in balance parameters ( p  > 0.05). The right-left heel maximum forces were lower in both groups with DPN compared to the control group ( p  < 0.05). In terms of spatiotemporal parameters of the gait, there was a difference between the groups only in step width and left single support line parameters ( p  < 0.05)., Conclusions: The results of this study indicate that the individuals with DPN have an increased step width, their left single support line was shortened, and the maximum force on the heel decreased. The NP did not cause any change in balance and gait parameters.

Objective: To determine the prevalence of insomnia and the effectiveness of its treatment in patients with a painful form of diabetic polyneuropathy (DPN)., Material and Methods: Fifty patients with the painful form of DPN were randomly divided into 2 groups: the standard therapy group (ST) and the extended therapy group (ET). In the ST group, a single lesson on sleep hygiene was conducted, in the ET group there were 3-4 face-to-face individual sessions for the treatment of insomnia for two weeks. Both groups were interviewed at the time of hospitalization, after 3 and 6 months. The severity of polyneuropathy and the nature of neuropathic pain were assessed using the Neuropathic Neuropathy Impairment Score in the Lower Limbs (NIS-LL) and the Neuropathy Total Symptom Score - 9 (NTSS-9); the intensity of pain was assessed using a Visual Analog Scale (VAS). Sleep disorders were analyzed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI)., Results: Sleep disorders of varying severity were observed in 82% of patients in the initial survey. In both groups, improvement in sleep quality was noted during treatment, but significantly better results were in the ET group, the ISI score after 6 months was 7.15±2.08 for the ST group and 3.07±2.49 for the ET group ( p <0.0001). In the ST group, there was no significant decrease in the intensity of pain and the severity of polyneuropathy in dynamics. In the ET group, a significant decrease in NTSS-9 and VAS scores was found during the initial survey and after 6 months ( p <0.0001). The intensity of pain also significantly decreased in the ET group compared with the ST group ( p <0.0001) at the end of follow-up, which indicates the importance of sleep normalization in the treatment of neuropathic pain., Conclusion: Most patients with the painful form of DPN have insomnia. Treatment of insomnia has shown its effectiveness as part of a multimodal approach to the managing of neuropathic pain in DPN and improving the quality of life of patients.

Background: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are common complications of type 2 diabetes mellitus (T2DM). Although nerve conduction studies (NCS) and sympathetic skin response (SSR) can detect DPN, the more sensitive method for early diagnosis remains unclear. Furthermore, whether DPN can be used as a predictor for diabetic nephropathy needs clarification., Methods: We evaluated nerve conduction studies, sympathetic skin response, and the diabetic nephropathy indicator microalbuminuria (MAU) in 192 patients with type 2 diabetes mellitus and 50 healthy controls., Results: Patients with type 2 diabetes mellitus showed a lower sensory nerve conduction velocity (SCV), sensory active nerve potential (SNAP), motor nerve conduction velocity (MCV), and compound motor action potential (CMAP) than the controls on NCS. Abnormal rates for nerve conduction studies and sympathetic skin response were 75.0% and 83.3%, respectively, in patients with type 2 diabetes mellitus. Interestingly, 54.2% of patients with normal nerve conduction studies had an abnormal sympathetic skin response. Moreover, we found a positive correlation between sympathetic skin response and microalbuminuria for the first time. The abnormal rate of microalbuminuria was 53.8%, lower than that of abnormal nerve conduction studies or sympathetic skin response patients., Conclusion: Sympathetic skin response is a more sensitive method than nerve conduction studies for the early diagnosis of diabetic peripheral neuropathy. Abnormal sympathetic skin response might serve as an indicator for early diabetic nephropathy. Additionally, diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the development of type 2 diabetes mellitus., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Diabetic peripheral neuropathy (DPN) is one of the common chronic complications of diabetes, resulting in neuropathy of spinal nerve, cranial nerve, and vegetative nerve. Diabetic distal symmetric multiple neuropathy is the most representative lesion of DPN, including symptoms of bilateral limbs pain, numbness, and paresthesia, etc. DPN is one of the main reasons causing diabetic foot ulcer (DFU). Schwann cells (SCs) are the primary glia cells of the peripheral nervous system, which play very important role in repairing after nerve injury. As the target cells of chronic hyperglycemia, SCs' functions, including the formation of myelin sheath, the secretion of neurotrophic factors, energy supplying for the axon, and the guidance of axon regeneration, etc., are damaged under the action of high glucose. The destroyed functions of SCs can inhibit the repair of damaged nerves and accelerate the progress of DPN. Therefore, if the damage of high glucose to SCs can be effectively reduced, it will provide a new way for the treatment of DPN and DFU and reduce the morbidity of DFU. This review focuses on the function of SCs and its relationship with DPN.

Background: The anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of these complications. This study aims to investigate the association between renal function-related indicators and the occurrence of peripheral neuropathy and retinopathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) who currently have normal renal function., Methods: Patients with T2DM who met the criteria were selected from the MMC database and divided into diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR) groups, with a total of 859 and 487 patients included, respectively. Multivariate logistic regression was used to analyze the relationship between blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), urine albumin(ALB), albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and diabetic peripheral neuropathy and retinopathy. Spearman correlation analysis was used to determine the correlation between these indicators and peripheral neuropathy and retinopathy in diabetes., Results: In a total of 221 patients diagnosed with DPN, we found positive correlation between the prevalence of DPN and eGFR (18.2, 23.3, 35.7%, p  < 0.05). Specifically, as BUN (T1: references; T2:OR:0.598, 95%CI: 0.403, 0.886; T3:OR:1.017, 95%CI: 0.702, 1.473; p  < 0.05) and eGFR (T1: references; T2:OR:1.294, 95%CI: 0.857, 1.953; T3:OR:2.142, 95%CI: 1.425, 3.222; p  < 0.05) increased, the odds ratio of DPN also increased. Conversely, with an increase in Cr(T1: references; T2:OR:0.86, 95%CI: 0.56, 1.33; T3:OR:0.57, 95%CI: 0.36, 0.91; p  < 0.05), the odds ratio of DPN decreased. Furthermore, when considering sensitivity and specificity, eGFR exhibited a sensitivity of 65.2% and specificity of 54.4%, with a 95% confidence interval of 0.568-0.656., Conclusion: In this experimental sample, we found a clear positive correlation between eGFR and DPN prevalence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Chen, Chen and Wan.)

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Background: Diabetes Mellitus represents a major socio-economic issue both by influencing the patient's quality of life and also considering the impact on the healthcare system. Diabetic neuropathy is one of the main complications associated, in most cases being present from the moment of diagnosis. Considering the high incidence of diabetes among patients with biliodigestive surgical conditions, a thorough analysis of the evolution and management of these patients is necessary. Materials and Methods: The association between the evolution of diabetic patients with biliodigestive conditions and diabetic neuropathy as well as risk criteria and associated complications were analyzed in a descriptive, correlational study (314 patients) conducted in the Dr. I. Cantacuzino Clinical Hospital during 2020-2022. In the study, the patients were distributed into two groups, one consisting in patients without diabetes mellitus (control group) and the second further subdivided into two groups of study, first (2a) containing patients with type II with diabetic neuropathy and high and medium risk rate, and a second one (2b) including patients with diabetes mellitus type II with confirmed neuropathy and low risk rate. Clinical and laboratory evaluations were performed and management protocols applied. Results: Statistically significant correlations were highlighted between diabetic neuropathy and the variables tested which were subsequently combined to achieve a risk score and a management protocol. Conclusions: Diabetes mellitus associated with diabetic neuropathy represents a negative prognostic factor for the postoperative outcome being associated with high risk of morbidity and mortality. The risk score and the management protocol described as results of this study represent feasible solutions and a subservient instrument in preventing the occurrence of complications in patients with bilio-digestive surgical pathologies in order to improve the prognosis and survival of the patients., (Celsius.)

Painful diabetic neuropathy (PDN) is a serious and very common complication of diabetes mellitus (DM). It negatively affects the quality of life, increases morbidity and poses a financial burden on the health care system. Currently, treatment of PDN focuses on glycaemic control, while pathogenesis-oriented therapy has not yielded satisfactory results. The need to improve therapy remains. There is accumulating evidence on the potential benefit of nutritional interventions. This narrative review aims to examine the potential benefit of dietary and nutritional supplementation for PDN management. According to the preliminary research, supplementation with vitamin E, B-complex, omega-3 fatty acids, CoQ10 or N-acetylcysteine seems to be associated with promising results in improving PDN symptoms., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. N. Papanas has been an advisory board member of Astra-Zeneca, Boehringer Ingelheim, MSD, Novo Nordisk, Pfizer, Roche, Takeda, TrigoCare International; has participated in sponsored studies by Astra- Zeneca, Eli-Lilly, GSK, MSD, Novo Nordisk, Novartis, Sanofi-Aventis; has received honoraria as a speaker for Abbott, Astra-Zeneca, Boehringer Ingelheim, Eli-Lilly, ELPEN, Galenica, Medtronic, MSD, Mylan, Novo Nordisk, Pfizer, Sanofi-Aventis, Takeda, Vianex; and attended conferences sponsored by Astra-Zeneca, Coloplast, TrigoCare International, Eli-Lilly, ELPEN, Galenica, Novo Nordisk, MSD, Mylan, Boehringer Ingelheim, Pfizer, Sanofi-Aventis, Vianex. Kyriaki Apergi is employed by the European Food Safety Authority (EFSA) in the Food Ingredients and Packaging Unit & Methodology and Scientific Support Unit that provides scientific and administrative support to the Panel of Food Contact Materials, Enzymes and Processing Aids. However, the present article is published under the sole responsibility of the author and may not be considered as an EFSA scientific output. The positions and opinions presented in this article are those of the author alone and do not necessarily represent the views or scientific work of EFSA. To learn about the views or scientific outputs of EFSA, please consult its website under http://www.efsa.europa.eu., (Thieme. All rights reserved.)

Exploitation of nanocarriers provides a compartment for enclosing drugs to protect them from degradation and potentiate their therapeutic efficiency. In the current study, amitriptyline- and liraglutide-loaded proniosomes were constructed for management of diabetic neuropathy, a serious complication associated with diabetes, that triggers spontaneous pain in patients and results in impaired quality of life. The developed therapeutic proniosomes were extensively characterized via dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and Fourier transform-infrared spectroscopy. High entrapment efficiency could be attained for both drugs in the proniosomes, and the reconstituted amitriptyline- and liraglutide-loaded niosomes possessed spherical morphology and particle sizes of 585.3 nm and 864.4 nm, respectively. In a diabetic neuropathy rat model, oral administration of the developed amitriptyline- and liraglutide-loaded proniosomes significantly controlled blood glucose levels, reduced neuropathic pain, oxidative stress and inflammatory markers, and improved histological structure of the sciatic nerve as compared to the oral and subcutaneous administration of amitriptyline and liraglutide, respectively. Loading of the tricyclic antidepressant amitriptyline and the antidiabetic peptide liraglutide into proniosomes resulted in exceptional control over hyperglycemia and neuropathic pain, and thus could provide an auspicious delivery system for management of neuropathic pain and control of blood glucose levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetic neuropathy is an important long-term complication of diabetes. This study explored the hypothesis that hydrogen sulfide (H 2 S) ameliorates neuropathic pain by controlling antiapoptotic and pro-apoptotic processes. The effects of a slow-releasing H 2 S donor, GYY4137, on the expression of antiapoptotic and pro-apoptotic genes and proteins, such as B-cell lymphoma 2 (Bcl2) and Bcl-2-like protein 4 (Bax), as well as caspases, cyclooxygenase (COX)-1 and COX-2, monocytes/macrophages, and endothelial cells, in the spinal cord of male Sprague-Dawley rats with streptozotocin-induced peripheral diabetic neuropathy, were investigated using reverse transcription-PCR, western blot and immunohistochemistry. The antihypoalgesic activities of GYY4137 on diabetic rats were evaluated using the tail flick test. Treatment of diabetic rats with GYY4137 attenuated thermal hypoalgesia and prevented both the diabetes-induced increase in Bax mRNA expression ( p = 0.0032) and the diabetes-induced decrease in Bcl2 mRNA expression ( p = 0.028). The GYY4137-treated diabetic group had increased COX-1 ( p = 0.015), decreased COX-2 ( p = 0.002), reduced caspase-7 and caspase-9 protein expression ( p < 0.05), and lower numbers of endothelial and monocyte/macrophage cells ( p < 0.05) compared to the non-treated diabetic group. In summary, the current study demonstrated the protective properties of H 2 S, which prevented the development of neuropathy related behavior, and suppressed apoptosis activation pathways and inflammation in the spinal cord. H 2 S-releasing drugs could be considered as possible treatment options of diabetic peripheral neuropathy.

Background: Lumbosacral radiculoplexus neuropathy, also known as amyotrophy, is an uncommon monophasic disorder characterized by inflammation of the lumbosacral nerve roots and plexuses. Lumbosacral radiculoplexus neuropathy is usually associated with diabetes mellitus, is typically painful at presentation, and often associated with long-term residual neurologic deficits. We report a case of painless, nondiabetic lumbosacral radiculoplexus neuropathy in a young Chinese woman, who made a full recovery after treatment with intravenous immunoglobulin, adding an atypical case to the scarce literature on lumbosacral radiculoplexus neuropathy., Case Presentation: A 35-year-old Chinese woman presented to our emergency department with 1-week history of painless left lower limb weakness and numbness. Examination revealed weakness confined to the left lower limb but spanning various nerves and myotomes, with abnormal sensation. Clinical localization to the lumbosacral plexus was supported by neurodiagnostic tests, and magnetic resonance imaging of the lumbosacral plexus showed that the nerve roots were also involved. After treatment with intravenous immunoglobulin for nondiabetic lumbosacral radiculoplexus neuropathy, the patient had a full recovery., Conclusion: Our patient's case highlights that lumbosacral radiculoplexus neuropathy, an already rare disorder, can occur in the absence of diabetes mellitus and pain, making it even harder to recognize. A systematic and meticulous clinical approach, supported by intelligent selection of adjunctive tests, is required for localization and diagnosis. With an accurate diagnosis, our case also demonstrates that appropriate and prompt treatment can lead to complete recovery, despite previous reports suggesting a high prevalence of long-term residual deficits after lumbosacral radiculoplexus neuropathy., (© 2023. The Author(s).)

Background: Diabetes-related peripheral neuropathy (DPN) and limited joint mobility of the foot and ankle are implicated in the development of increased plantar pressures and diabetes-related foot ulcers. The extent of this relationship has not been conclusively established. We aimed to determine the relationship between ankle joint and first metatarsophalangeal joint dorsiflexion range of motion and DPN using a cross-sectional observational study design., Methods: Primary outcomes were DPN status, ankle joint range of motion (extended and flexed knee lunge tests), and nonweightbearing first metatarsophalangeal joint range of motion. Correlations were performed using Pearson r, and hierarchical regression analyses were undertaken to determine the independent contribution of DPN to the variance in dorsiflexion range of motion of ankle and first metatarsophalangeal joints using standardized β regression coefficients, controlling for age, sex, body mass index, diabetes duration, and hemoglobin A1c level., Results: One hundred one community-dwelling participants (mean ± SD age, 65.0 ± 11.2 years; 55 men; 97% type 2 diabetes; mean ± SD diabetes duration, 8.7 ± 7.8 years; 23% with DPN) were recruited. Diabetes-related peripheral neuropathy demonstrated significant correlations with reduced range of motion at the ankle joint (knee extended: r = -0.53; P < .001 and knee flexed: r = -0.50; P < .001) and the first metatarsophalangeal joint (r = -0.37; P < .001). Also, DPN made significant, unique contributions to the regression models for range of motion at the ankle joint (knee extended: r2 change = 0.121; β = -0.48; P < .001 and knee flexed: r2 change = 0.109; β = -0.45; P < .001) and first metatarsophalangeal joint (r2 change = 0.037; β = -0.26; P = .048)., Conclusions: These findings suggest that DPN contributes to reduced ankle and first metatarsophalangeal joint range of motion. Due to the established link between reduced ankle and first metatarsophalangeal joint range of motion and risk of diabetes-related foot ulcer, we recommend that clinicians assess dorsiflexion range of motion at these joints as part of routine foot assessment in people with diabetes, especially those with DPN. Globally, approximately 436 million adults aged 20 to 79 years are living with diabetes.1 Diabetes is the leading cause of lower-limb amputation and is associated with a lifetime incidence of diabetes-related foot ulcer (DFU) of up to 34%.2 Diabetes-related peripheral neuropathy (DPN) affects approximately 30% to 50% of people with diabetes3 and is one of the most significant risk factors for the development of DFU and amputation.4 Diabetes-related peripheral neuropathy occurs as a result of neural ischemia and perineural edema causing neural demyelination, affecting nerve conductivity.5 In the presence of DPN, intrinsic foot muscle wasting can lead to the development of foot deformities such as digital clawing, which, when coupled with structural and functional changes to the skin, make it less resistant to shear forces and further increase plantar pressure and risk of DFU.6,7.

Aims: To investigate the cross-sectional association between deep and superficial diabetic neuropathy, postural impairment assessed by wearable inertial sensors, and the risk of fall among patients with diabetic foot., Methods: Diabetic patients attending a University Podiatric Clinic were evaluated for the presence of deep and superficial peripheral neuropathy in sensory tests. Postural impairment was assessed using a wearable inertial sensor, and the evaluation of balance/gait and risk of fall was determined by the Tinetti Scale and Downton Index, respectively. Glycemic control was measured by glycated haemoglobin concentration and fasting glycaemia. The postural parameters measured were the anteroposterior and medio-lateral sway of the center of mass (CoM) and the sway area (area traveled by the CoM per second). The results were analyzed through a logistic regression model to assess those posture variables mostly significantly associated with neuropathy and risk of fall scales., Results: A total of 85 patients were evaluated. Spearman's rank correlation coefficients showed a strong and significant relationship (p < 0.05) between deep diabetic neuropathy assessed by Semmes-Weinstein monofilament, diapason and biothensiometer and postural alterations, whereas no significant correlations between superficial (painful sensitivity) neuropathy and the postural parameters. The sway path of the displacement along the anterior-posterior axis recorded during tests performed with eyes open and feet close together were significantly (p < 0.05) correlated with a poor glycemic (glycated haemoglobin concentration) control and each other with all diabetic neuropathy tests, fall risk scales, muscular weakness, ankle joint limitation and history of ulcers., Conclusions: The results support the existence of a strong association between alterations of the deep somato-sensitive pathway (although depending on the tool used to measure peripheral neuropathy), glycemic control and balance impairments assessed using a wearable sensors. Wearable-based postural analysis might be part of the clinical assessment that enables the detection of balance impairments and the risk of fall in diabetic patients with diabetic peripheral neuropathy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Aims: To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population., Methods: This cross-sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed., Results: A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high-density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C-peptide, and uric acid were negatively associated with DPN., Conclusions: Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low-income, and undereducated patients., (© 2023 John Wiley & Sons Ltd.)

Aim: This study aims to investigate the association among metformin use, vit B12 deficiency, and DPN occurrence in diabetes., Methods: This retrospective, propensity-matched cohort study was performed using National Health Insurance Service database - National Sample Cohort in South Korea. Study 1 analyzed DPN incidence according to vit B12 deficiency and study 2 analyzed vit B12 deficiency incidence according to the presence/absence of DPN. Moreover, we compared the results with respect to metformin use., Results: In study 1, DPN incidence per 10000 person-year (PY) was 179.7 and 76.6 in the vit B12 and non-vit B12 deficiency groups, respectively. The adjusted HR was 1.32 (95% CI; 1.21-1.44, P < 0.05) and metformin use elicited a more significant effect of DPN occurrence in patient with vit B12 deficiency (HR: 5.76 (95% CI; 5.28-6.29). In study 2, vit B12 deficiency incidence per 10000 PY was 250.6 and 129.4 in the DPN and non-DPN groups, respectively. The adjusted HR was 2.44 (95% CI; 2.24-2.66, P < 0.05), however, metformin prescription was associated with the reduced incidence of vit B12 deficiency in DPN patients (HR 0.68 (95% CI; 0.62-0.74, P < 0.05)., Conclusion: DPN occurrence increased in diabetes with vit B12 deficiency and the incidence of vit B12 deficiency was also high in DPN patients. However, metformin showed opposite effects in both cohorts. Further studies clarifying the causal relationship among DPN occurrence, vit B12 deficiency, and metformin use are warranted., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: Sudomotor dysfunction is linked to small fibers damage. We investigated sudomotor dysfunction in a large group of participants with diabetes, prediabetes, and nondiabetic healthy subjects. This study aimed to complete knowledge on sudomotor dysfunction in this population, especially regarding the threshold values for the electrochemical skin conductance (ESC) and factors affecting it., Materials and Methods: A total of 690 volunteers in four groups were included in the study (type 1 [T1DG]: n = 80, 61.3% women; type 2 diabetes [T2DG]: n = 438, 63.5% women; prediabetes [Pre-DG]: n = 88, 80.7% women; healthy control [HC-G]: n = 84, 67.5% women). All subjects were investigated for clinical diabetic peripheral polyneuropathy and sudomotor dysfunction. The characteristics of participants obtained from outpatient records were evaluated. We used the Sudoscan device to measure ESC which was normalized for BMI, to improve the discriminative capability of the method., Results: Diabetic polyneuropathy was found in 17.5% of T1DG, 27.4% of T1DG, and 10.2% of Pre-DG. The mean ESC/BMI was lower in subgroups with diabetic polyneuropathy than those without. Mean ESC/BMI was lowest in T2DG and highest in HC-G but comparable in T1DG and Pre-DG. We accepted the "mean ESC/BMI-1 SD" in the HC-G as the threshold for sudomotor dysfunction. Accordingly, the prevalence of sudomotor dysfunction was 18.8%, 44.3%, 59.1%, and 15% in T1DG, T2DG, Pre-DG, and HC-G, respectively. In T2DG, sudomotor dysfunction was found in 66.7% of persons with retinopathy, of which 56.3% had clinical diabetic polyneuropathy. The prevalence of sudomotor dysfunction in subjects with peripheral artery disease, chronic kidney disease, cardiovascular disease, and hypertension was 46.7%, 47.4%, 43.4%, and 50%, respectively, and 42.9%, 38.9%, 45.5%, and 37.3% of whom in the same order detected with clinical diabetic polyneuropathy. Considering the entire group, a logistic regression model demonstrated that the variables associated with SMD were: retinopathy (OR: 2.969; 95% CI: 1.723, 5.114), female gender (OR: 1.952; 95% CI: 1.287, 2.962), and e-GFR (OR: 0.989; 95% CI: 0.981, 0.998). Since the rate of complications was very low in T1DG, excluding this group, a new model similarly revealed that retinopathy and female gender were associated with SMD, however, the association with e-GFR was disappeared., Conclusion: The prevalence of sudomotor dysfunction is high when established peripheral polyneuropathy was present in diabetes. Even though, sudomotor dysfunction can also occur before clinical polyneuropathy in both types of diabetes (T1DG: 18.8%, T2DG 44.3%), prediabetes (59.1%), and nondiabetic healthy subjects (15%). The variables associated with sudomotor dysfunction were retinopathy and female sex. Normalization of ESC for BMI would be a beneficial approach. However, before this method is included in the routine screening programs for diabetic polyneuropathy, large-scale and prospective studies are required to reach a consensus on the pathological threshold values., Competing Interests: Declaration of Competing Interest The authors: B.F.C., S.C., C.I., E.B., H.I., and I.S. declared that they have no conflict of interest. J-H.C. was former Medical Director of IMPETO Medical between 2010 and 2021., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying pathogenesis of these complications are unclear. In this study, we optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background. Glomeruli and sciatic nerve transcriptomic data from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both complications in T1D and T2D mice. Gene-level analysis identified a high degree of concordance in shared differentially expressed genes (DEGs) in both complications and across diabetes type when using mice from the same cohort and genetic background. As we have previously shown a low concordance of shared DEGs in DPN when using mice from different cohorts and genetic backgrounds, this suggests that genetic background may influence diabetic complications. Collectively, these findings support the role of inflammation and indicate that genetic background is important in complications of both T1D and T2D., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Aims: Increasing numbers of reports link vitamin D deficiency to diabetic peripheral neuropathy (DPN), yet evidence regarding neurological deficits and electromyogram is scarce. The present multi-centre study sought to investigate these associations based on objective quantifications., Materials and Methods: Information on DPN-related symptoms, signs, all diabetic microvascular complications, and nerve conduction abilities (quantified by nerve conduction amplitude and velocity, F-wave minimum latency (FML) of peripheral nerves) were collected from a derivation cohort of 1192 patients with type 2 diabetes (T2D). Correlation, regression analysis, and restricted cubic splines (RCS) were used to explore linear and non-linear relationships between vitamin D and DPN, which were validated in an external cohort of 223 patients., Results: Patients with DPN showed lower levels of vitamin D than those without DPN; patients with vitamin D deficiency (<30 nmol/L) tended to suffer more DPN-related neurological deficits (paraesthesia, prickling, abnormal temperature, ankle hyporeflexia, and distal pall hypoesthesia correlating with MNSI-exam score (Y = -0.005306X + 2.105, P = 0.048). Worse nerve conduction abilities (decreased motor nerve amplitude, sensory nerve amplitude, motor nerve velocity, and increased FML) were also observed in these patients. Vitamin D had a significant threshold association with DPN (adjusted OR = 4.136, P = 0.003; RCS P for non-linearity = 0.003) and correlates with other microvascular complications (diabetic retinopathy and diabetic nephropathy)., Conclusions: Vitamin D is associated with the conduction ability of peripheral nerves and may have a nerve- and threshold-selective relationship with the prevalence and severity of DPN among patients with T2D., (© 2023 John Wiley & Sons Ltd.)

Objective: We aimed to investigate whether serum cortisol associate with diabetic microvascular compliments in patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: The subjects were recruited from hospitalized patients with T2DM from 2019 to 2021. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to cortisol quartiles were obtained by multiple logistic regression analysis., Results: (1) Cortisol level was positively correlated with the severity of microalbuminuria. The OR (95% CI) of microalbuminuria and macroalbuminuria in the last quartile were 3.396 (2.030, 5.682) and 8.407 (3.726, 18.971) compared with the first quartile (p < 0.001). (2) Cortisol level was positively correlated with the severity of diabetic retinopathy (DR). The OR (95% CI) of non-proliferative diabetic retinopathy group (NPDR) and proliferative diabetic retinopathy group (PDR) in the last quartile were 2.007 (1.401, 2.875) and 7.122 (2.525, 20.090) compared with the first quartile. (3) Elevated cortisol level was associated with diabetic peripheral neuropathy. The OR (95% CI) of diabetic peripheral neuropathy (DPN) in the last quartile was 1.956 (1.371, 2.792) and that in the third quartile was 1.854 (1.319, 2.608)., Conclusions: High serum cortisol levels were significantly associated with diabetic microvascular compliments in inpatients. Its causality remains to be further studied., Clinical Trial Registration Number: ChiCTR2100051749., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: A variety of medications are available to manage painful diabetic peripheral neuropathy (DPN), but the proper treatment remains challenging. Accordingly, various neuromodulation modalities have been used. However, no prospective clinical trials have evaluated the use of scrambler therapy (ST) in painful DPN. This study aimed to explore the long-term effects of ST in managing painful DPN., Methods: The patients received 10 consecutive STs of 45 minutes every 1 to 2 days. The primary outcome was pain score. We measured the visual analog scale (VAS) pain scores at baseline, during ST, immediately after ST, and at 1, 2, 3, and 6 months after ST. The secondary outcomes were Michigan Neuropathy Screening Instrument (MNSI), Semmes-Weinstein monofilament test, and Leeds Assessment of Neuropathic Symptoms and Signs pain scores, which were measured at baseline, immediately after ST, and at 1, 2, 3, and 6 months after ST., Results: VAS scores showed significant improvement at the 8th, 9th, and 10th sessions during ST and 1 month after ST. The MNSI self-report component score was decreased 1 month after the ST. However, all other outcomes did not show significant differences compared to the baseline., Conclusion: ST may have short-term effects and limited long-term effects on painful DPN., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Peripheral neuropathy is a common microvascular complication in diabetes and a risk factor for the development of diabetic foot ulcers and amputations. Vibrasense (Ayati Devices) is a handheld, battery-operated, rapid screening device for diabetic peripheral neuropathy (DPN) that works by quantifying vibration perception threshold (VPT). In this study, we compared Vibrasense against a biothesiometer and nerve conduction study for screening DPN., Methods: A total of 562 subjects with type 2 diabetes mellitus underwent neuropathy assessments including clinical examination, 10-g monofilament test, VPT evaluation with Vibrasense and a standard biothesiometer. Those with an average VPT ≥ 15 V with Vibrasense were noted to have DPN. A subset of these patients (N = 61) underwent nerve conduction study (NCS). Diagnostic accuracy of Vibrasense was compared against a standard biothesiometer and abnormal NCS., Results: Average VPTs measured with Vibrasense had a strong positive correlation with standard biothesiometer values (Spearman's correlation 0.891, P < 0.001). Vibrasense showed sensitivity and specificity of 87.89% and 86.81% compared to biothesiometer, and 82.14% and 78.79% compared to NCS, respectively., Conclusions: Vibrasense demonstrated good diagnostic accuracy for detecting peripheral neuropathy in type 2 diabetes and can be an effective screening device in routine clinical settings., Trial Registration: Clinical trials registry of India (CTRI/2022/11/047002). Registered 3 November 2022.  https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=76167 ., (© 2023. The Author(s).)

Aims/introduction: Distal symmetric polyneuropathy (DSPN) is a common complication of type 2 diabetes mellitus, but the underlining mechanisms have not yet been elucidated. The current study was designed to screen the feature metabolites classified as potential biomarkers, and to provide deeper insights into the underlying distinctive metabolic changes during disease progression., Materials and Methods: Plasma metabolite profiles were obtained by the ultra-high liquid chromatography coupled to tandem mass spectrometry method from healthy control participants, patients with type 2 diabetes mellitus and patients with DSPN. Potential biomarkers were selected through comprehensive analysis of statistically significant differences between groups., Results: Overall, 938 metabolites were identified. Among them, 12 metabolites (dimethylarginine, N6-acetyllysine, N-acetylhistidine, N,N,N-trimethyl-alanylproline betaine, cysteine, 7-methylguanine, N6-carbamoylthreonyladenosine, pseudouridine, 5-methylthioadenosine, N2,N2-dimethylguanosine, aconitate and C-glycosyl tryptophan) were identified as the specific biomarkers. The content of 12 metabolites were significantly higher in the DSPN group compared with the other two groups. Additionally, they showed good performance to discriminate the DSPN state. Correlation analyses showed that the levels of 12 metabolites might be more closely related to the glucose metabolic changes, followed by the levels of lipid metabolism., Conclusions: The finding of the 12 signature metabolites might provide a novel perspective for the pathogenesis of DSPN. Future studies are required to test this observation further., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: Diabetic plexopathy is among the most unusual and disabling complication type 2 diabetic mellitus (T2DM) causing major suffering among affected individuals. The clinical presentation includes asymmetric muscle atrophy, weakness, and pain, typically associated with sudden weight loss. In part due to its rarity, this condition can be easily missed with serious consequences including potentially fatal complications., Methods and Results: A single case report of a 59-year-old woman with T2DM complicated by a lumbosacral plexopathy that presented with unusual clinical signs, symptoms and metabolic changes including (i) a life-threatening cardiac arrest due to a massive saddle pulmonary embolism (PE) secondary to a lower limb deep venous thrombosis ipsilateral to the plexopathy and (ii) an unexpected partial spontaneous remission of T2DM., Conclusions: This case highlights the need for increased awareness and improved investigation and understanding of the pathogenesis and management of diabetic plexopathy, especially in rehabilitation settings for optimizing functional outcomes from rehabilitation input. Implications for rehabilitationDiabetic lumbosacral plexopathy (DLSP) is a distinct cause of neurological impairment requiring rehabilitation with a different natural history and prognosis. Its incidence almost three times higher than that of other common inflammatory neuropathies such as Guillain-Barré.Early recognition of DLSP in order to provide interventions, assessment, and therapeutic strategies in Rehabilitation.Diabetes plexopathy should remain an important consideration in the differential diagnoses when assessing any patient with diabetes presenting with acute pain and weakness in the extremities.

Objective: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity., Research Design and Methods: We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S., Results: A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S., Conclusions: Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN., (© 2023 by the American Diabetes Association.)