Diabetic Neuropathy Research Articles

ID: 335010 10kHz SCS Treatment of Painful Diabetic Neuropathy: Results Combining Dermatomal Dysesthesias and Limb Sensory Assessments

ID: 335010 10kHz SCS Treatment of Painful Diabetic Neuropathy: Results Combining Dermatomal Dysesthesias and Limb Sensory Assessments

Single simple question in axonal polyneuropathy.

The single simple question (SSQ), "What percentage of normal (0%-100%) do you feel regarding your disease?" has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes. A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch-built Overall Disability Scale (RODS). The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = -.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%-70%, and 34% with SSQ >70%). The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length-dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP.

ID: 335559 Refractory Painful Diabetic Neuropathy with Concomitant Renal Failure Treated with Spinal Cord Neuromodulation

ID: 335559 Refractory Painful Diabetic Neuropathy with Concomitant Renal Failure Treated with Spinal Cord Neuromodulation

Mechanistic Insights into the Neuroprotective Effects of Natural Products in Diabetic Neuropathy

Diabetic neuropathy (DN) is one of the prominent complications of diabetes, which can result in pain, impaired movement, and even amputation. There are different types of DN, which can cause pain in fatal situations. In addition to altering insulin signaling, hyperglycemia and dyslipidemia cause a number of pathological changes in vascular cells, glia, as well as in neurons that can cause nerve damage and, in the end, neuropathy. Diabetic neuropathy has a poor prognosis since it doesn't show symptoms for years after diabetes starts. Despite the abundance of medications on the market, pharmacological ineffectiveness and a wide spectrum of adverse effects restrict adherence. As a result, there is a growing need to find novel compounds that show promising effects in the management of severe pain disorders. The most promising sources of novel chemical entities with potential use in medicine continue to be plant-derived products. Those products influenced the various signaling pathways, including PI3K/AKT pathway, MAPK pathway, Oxidative stress, TNF-α signaling, cyclo-oxygenase (COX 2) pathway and other molecular pathways to act as novel therapeutics for diabetic neuropathy. Basically, this mechanistic approach is implemented to improve neuroprotective activity, especially phytoconstituents derived from bioactive compounds. As neurodegenerative diseases have a complicated pathogenesis, the medications that are available on the market only treat the symptoms. Therefore, it would be highly desirable to design pharmacophores for the management of DN, with bioactive substances that have strong neuroprotective effects, using a multi-target strategy.

Ameliorative Effect of Hedysarum polybotrys Polysaccharide on Neural Tissue Fibrosis in Diabetic Peripheral Neuropathy Mice and its Mechanisms

Objective: This study aimed to investigate the role of Hedysarum polybotrys polysaccharide (HPS) in ameliorating neural tissue fibrosis in diabetic peripheral neuropathy (DPN) mice. Methods: Fifty DPN mice were selected and randomly divided into five groups (n = 10), which were the model group, positive control group (receiving only 4 mg/(kg-d) of α-lipoic acid), high-dose HPS group (200 mg/(kg-d) of HPS was given per day), medium-dose HPS group (100 mg/(kg-d) of HPS was given per day), and low-dose HPS group (50 mg/(kg-d) of HPS given daily). In addition, non-diabetic C57BL/6 wild-type mice were selected as the normal group (n = 10). The expression levels of Keap1 and Nrf2 proteins and their mRNAs in the sciatic nerve tissues of mice in each group were analyzed by Western blot technique and real-time fluorescence quantitative PCR. Results: Compared with the normal group, the expression of Keap1 protein and mRNA was increased, while the expression of Nrf2 protein and mRNA was decreased in the sciatic nerve of mice in the model group (P &lt; 0.05). Compared with the model group, Keap1 protein and mRNA expression decreased, while Nrf2 protein and mRNA expression increased in the control and high and medium dose HPS groups of mice (P &lt; 0.05). Conclusion: HPS may inhibit fibrosis of neural tissue and ameliorate nerve injury in DPN mice by regulating the Keap1/Nrf2 signaling pathway. This effect was associated with enhanced antioxidant capacity, promotion of Nrf2 activation, and increased antioxidant gene expression by HPS. Therefore, HPS has a potential therapeutic value to ameliorate DPN-associated nerve injury.

Bone marrow mesenchymal stem cell and mononuclear cell combination therapy in patients with type 2 diabetes mellitus: a randomized controlled study with 8-year follow-up.

To investigate the long-term effects of combining bone marrow mesenchymal stem cells (MSCs) with mononuclear cells (MCs) in the treatment of type 2 diabetes mellitus (T2DM). T2DM patients were divided into the combination group (Dual MSC + MC, n = 33), the mononuclear cell group (MC-Only, n = 32) and the control group (Control, n = 31). All groups were treated with insulin and metformin. The Dual MSC + MC group additionally received MSC and MC infusion and the MC-Only group additionally received MC infusion. The patients were followed up for 8 years. The primary endpoint was the C-peptide area under the curve (C-p AUC) at 1 year. This study was registered with clinicaltrial.gov (NCT01719640). A total of 97 patients were included and 89 completed the follow-up. The area under the curve of C-peptide of the Dual MSC + MC group and the MC-Only group was significantly increased (50.6% and 32.8%, respectively) at 1 year. After eight years of follow-up, the incidence of macrovascular complications was 13.8% (p = 0.009) in the Dual MSC + MC group and 21.4% (p = 0.061) in the MC-Only group, while it was 44.8% in the Control group. The incidence of diabetic peripheral neuropathy (DPN) was 10.3% (p = 0.0015) in the Dual MSC + MC group, 17.9% (p = 0.015) in the MC-Only group, and 48.3% in the Control group. The combination of MSC and MC therapy can reduce the incidence of chronic diabetes complications and improves metabolic control with mild side effects in T2DM patients.

A Probiotic Mixture Decreases Neuropathy and Oxidative Stress Markers in Diabetic Rats

Diabetic neuropathy (DN) is a type of nerve damage caused by long-term hyperglycemia in diabetes mellitus (DM). The gut microbiota alters in DM. Therefore, improvement of the gut flora may affect neuropathic pain and oxidative biomarkers' responsiveness to the probiotic treatment. The present study aimed to assess the effects of probiotic supplementation on neuropathic pain and oxidative stress biomarkers in diabetic rats’ serum. Forty-eight rats (200-250 g) were randomly divided into four groups (n = 12 per group) to examine the effects of the probiotics mixture as follows: the control group (CO), and the diabetic groups received 1 ml probiotics mixture (DP) containing &lt;em&gt;Lactobacillus rhamnosus&lt;/em&gt;, &lt;em&gt;Lactobacillus acidophilus&lt;/em&gt;, &lt;em&gt;Lactobacillus delbrueckii&lt;/em&gt;, &lt;em&gt;Lactobacillus plantarum&lt;/em&gt;, and &lt;em&gt;Bifidobacterium bifidum&lt;/em&gt; (10&lt;sup&gt;9&lt;/sup&gt; CFU of each), 100 mg/kg Gabapentin (DG), or normal saline (DM) daily. The study used animals with plasma glucose concentrations between 70 and 100 mg/dl. Behavioral tests, including mechanical allodynia, cold allodynia, and thermal hyperalgesia, were used to evaluate the pain on days 1, 4, 7, 14, and 21 of the study. After that, the serum's biochemical analysis was completed. Taking the probiotics mixture decreased mechanical and cold allodynia as well as thermal hyperalgesia. The probiotics group also showed significant reductions in lipid peroxidation levels and increases in total antioxidant capacity (TAC) and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities compared to the DM group. Our results showed that supplementation with the probiotics mixture could reduce pain-related behaviors in diabetic rats by enhancing the antioxidant capacity in their serum.

Preparation and evaluation of sustained release microspheres for the treatment of diabetic neuropathy

This study aimed to prepare and evaluate sustained release microspheres for the treatment of diabetic neuropathy using Various polymers including sodium alginate, ethyl cellulose, HPMC K100, Carbopol 934, and Eudragit L-100-55. Polymers were employed to assess their impact on several crucial parameter’s entrapment efficiency, production yield Particle size analysis, swelling index, in vitro dissolution, and release kinetics. The production yield of microspheres varied depending on the polymer used, with some polymers performing in advanced yields. Entrapment effectiveness was set up to be optimal with certain polymer combinations. Particle size analysis indicated that the microspheres were within the asked range for controlled release operations. The swelling index showed polymer-dependent lump actions. In vitro dissolution studies demonstrated sustained medicine release over time, with different polymers impacting both the release rate and profile. medicine release kinetics analysis revealed that the release followed specific models, reflecting the commerce between the microsphere matrix and the medicine.

Redefining C-peptide: Therapeutic Potential in Mitigating Diabetic Microvascular Complications

This review examines the changing insights into C-peptide and its potential for therapeutic actions against the backdrop of diabetic microvascular complications. C-peptide, formerly regarded as just a byproduct of insulin production, has recently surfaced as a bioactive peptide with important physiological effects. Findings indicate that C-peptide has anti-inflammatory and antioxidant capabilities, strengthens glucose utilization, and raises insulin sensitivity. Trial results for C-peptide replacement therapy show hope for treating diabetic neuropathy and nephropathy conditions. The article reviews the influence of C-peptide on cells, focusing on interactions with cell surface receptors and the stimulation of signaling molecules inside cells. C-peptide's role in generating nitric oxide, activating Na+K+ATPase, and improving the flow of blood in microvessels is emphasized. The review explores how C-peptide affects red blood cell deformability and its potential capabilities in reducing multiple diabetic complications. Besides, the article examines current research into C-peptide analogs that have a long-lasting effect and clinical trials that assess C-peptide replacement therapy. ErsattaTM, a new generation of weekly dosage disease-modifying replacement peptides, is seen as a promising advance in the treatment of chronic diabetes complications. Overall, this review stresses the increased acceptance of C-peptide as a powerful agent for the management of microvascular complications in diabetes, giving hope for superior results in patients with both type 1 and potentially type 2 diabetes.

Effects of adipose tissues on the relationship between type 2 diabetes mellitus and reduced heart rate variability: mediation analysis.

Type 2 diabetes mellitus (T2DM) is associated with decreased heart rate variability (HRV) with an unclear intermediate mechanism. This study aimed to conduct mediation analysis to explore the impact of various adipose tissues on the relationship between T2DM and HRV. A total of 380 participants were enrolled for analysis, including 249 patients with T2DM and 131 non-diabetic controls. The thicknesses of four adipose tissues (subcutaneous, extraperitoneal, intraperitoneal, and epicardial) were measured by abdominal ultrasound or echocardiography respectively. HRV was assessed by 24-hour Holter for monitoring both frequency domain indices (LF, HF, and LF/HF) and time domain indices (SDNN, SDANN, SDNN index, rMSSD and pNN50). Mediation analysis was used toexamine whether adipose tissues mediated the relationship between T2DM and each index of HRV. Then, a latent variable - HRV burden - was constructed by structural equation model with selected HRV indices to comprehensively assess the whole HRV. Compared to non-diabetic controls, patients with T2DM exhibited a significant reduction in indices of HRV, and a remarkable increase in the thicknesses of extraperitoneal, intraperitoneal, and epicardial adipose tissues. Mediation analysis found significant indirect effects of T2DM on six indices of HRV, including HF, SDNN, SDANN, SDNN index, rMSSD, and pNN50, which was mediated by epicardial adipose tissue rather than other adipose tissues, with the mediation proportions of 64.21%, 16.38%, 68.33%, 24.34%, 24.10% and 30.51%, respectively. Additionally, epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV burden (24.26%), which composed by SDNN, SDNN index, rMSSD, and pNN50. Epicardial adipose tissue partially mediated the relationship between T2DM and reduced HRV, which reinforces the value of targeting heart-specific visceral fat to prevent cardiac autonomic neuropathy in diabetes.

Glycemic variability’s impact on painful diabetic peripheral neuropathy in type 2 diabetes patients

Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN.

Update on Biomarkers of Chronic Inflammatory Processes Underlying Diabetic Neuropathy.

There is an increasing prevalence of diabetes mellitus (DM), particularly type 2 DM (T2DM), and its associated complications. T2DM is linked to insulin resistance, chronic inflammation, and oxidative stress, which can lead to both macrovascular and microvascular complications, including peripheral diabetic neuropathy (PDN). Inflammatory processes play a key role in the development and progression of T2DM and its complications, with specific markers like C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor (TNF)-α being associated with increased risk. Other key inflammatory markers such as nuclear factor kappa B (NF-κB) are activated under hyperglycemic and oxidative stress conditions and contribute to the aggravation of PDN by regulating inflammatory gene expression and enhancing endothelial dysfunction. Other important roles in the inflammatory processes are played by Toll-like receptors (TLRs), caveolin 1 (CAV1), and monocyte chemoattractant protein 1 (MCP1). There is a relationship between vitamin D deficiency and PDN, highlighting the critical role of vitamin D in regulating inflammation and immune responses. The involvement of macrophages in PDN is also suspected, emphasizing their role in chronic inflammation and nerve damage in diabetic patients. Vitamin D supplementation has been found to reduce neuropathy severity, decrease inflammatory markers, and improve glycemic control. These findings suggest that addressing vitamin D deficiency could offer therapeutic benefits for PDN. These molecular pathways are critical in understanding the pathogenesis of DM complications and may offer potential biomarkers or therapeutic targets including anti-inflammatory treatments, vitamin D supplementation, macrophage phenotype modulation, and lifestyle modifications, aimed at reducing inflammation and preventing PDN. Ongoing and more extensive clinical trials with the aim of investigating anti-inflammatory agents, TNF-α inhibitors, and antioxidants are needed to advance deeper into the understanding and treatment of painful diabetic neuropathy.

Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy.

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.

Biomarkers and Novel Therapies of Diabetic Neuropathy: An Updated Review.

Diabetic neuropathy is a persistent consequence of the biochemical condition known as diabetes mellitus. As of now, the identification and management of diabetic neuropathy continue to be problematic due to problems related to the safety and efficacy of existing therapies. This study examines biomarkers, molecular and cellular events associated with the advancement of diabetic neuropathy, as well as the existing pharmacological and non-pharmacological treatments employed. Furthermore, a holistic and mechanism-centric drug repurposing approach, antioxidant therapy, Gene and Cell therapies, Capsaicin and other spinal cord stimulators and lifestyle interventions are pursued for the identification, treatment and management of diabetic neuropathy. An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer using the keywords "Diabetic Neuropathy", "Biomarkers", "Cellular and Molecular Mechanisms", and "Novel Therapeutic Targets".Thus, we may conclude that non-pharmacological therapies along with palliative treatment, may prove to be crucial in halting the onset of neuropathic symptoms and in lessening those symptoms once they have occurred.

Diosmin and Hesperidin Have a Protective Effect in Diabetic Neuropathy via the FGF21 and Galectin-3 Pathway.

Background and Objectives: This study aimed to investigate the protective effect of diosmin and hesperidin in diabetic neuropathy using a rat model, focusing on their impact on nerve regeneration through the fibroblast growth factor 21 (FGF21) and galectin-3 (gal3) pathway. Materials and Methods: Forty adult male Wistar rats were used in this study. Diabetes was induced using streptozotocin (STZ), and the rats were divided into control, diabetes and saline-treated, diabetes and diosmin + hesperidin (150 mg/kg) treated, and diabetes and diosmin + hesperidin (300 mg/kg) treated groups. Electromyography (EMG) and inclined plane testing were performed to assess nerve function and motor performance. Sciatic nerve sections were examined histopathologically. Plasma levels of FGF21, galectin-3, and malondialdehyde (MDA) were measured as markers of oxidative stress and inflammation. Results: Diabetic rats treated with saline displayed reduced nerve conduction parameters and impaired motor performance compared to controls. Treatment with diosmin and hesperidin significantly improved compound muscle action potential (CMAP) amplitude, distal latency, and motor performance in a dose-dependent manner. Histopathological examination revealed decreased perineural thickness in treated groups. Additionally, treatment with diosmin and hesperidin resulted in increased plasma FGF21 levels and reduced plasma levels of galectin-3 and MDA, indicating decreased oxidative stress and inflammation. Conclusions: Diosmin and hesperidin exhibited protective effects in diabetic neuropathy by promoting nerve regeneration, enhancing nerve conduction, and improving motor performance. These effects were associated with modulation of the FGF21 and galectin-3 pathway. These findings suggest that diosmin and hesperidin may hold potential as adjunctive therapies for diabetic neuropathy.

High-Concentration Capsaicin Topical System for Painful Diabetic Peripheral Neuropathy

High-Concentration Capsaicin Topical System for Painful Diabetic Peripheral Neuropathy

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic β-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

Expression of microRNA-27b in type 2 diabetic patients and relation to microvascular complications

ABSTRACT In this study, we aimed to explore whether circulating microRNA-27b (miR-27b) is affected in diabetic patient with microvascular complications Methods This study was conducted on 90 participants, 30 had type 2 diabetes with chronic limb ischemia, 30 diabetics without chronic limb ischemia and 30 healthy controls. The relative expression of microRNA 27b was assessed in the patient groups and its relation between diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). Results Concerning relation between miR-27b and other microvascular complications, DR & DN, miR-27b plasma expression showed no significant difference between T2DM patients with increased VPT compared to those with normal VPT. Comparably, there was no significant difference in the plasma miR-27b expression between patients with DR and those with normal fundus examination. Additionally, neither DR nor VPT correlated with plasma miR-27bexpression. Conclusion Plasma miR-27b expression showed no change between the patient groups and there was no correlation with microvascular complications and miR-27b expression.

Interconnections between diabetic corneal neuropathy and diabetic retinopathy: diagnostic and therapeutic implications.

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus. Diabetic corneal neuropathy refers to the progressive damage of corneal nerves. Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature. However, growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit, which includes both the retinal vascular structures and neural tissues. Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening. However, diabetic corneal neuropathy is commonly overlooked and underdiagnosed, leading to severe ocular surface impairment. Several studies have found that these two conditions tend to occur together, and they share similarities in their pathogenesis pathways, being triggered by a status of chronic hyperglycemia. This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy, whether diabetic corneal neuropathy precedes diabetic retinopathy, as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy. We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

Establishment and external validation of an early warning model of diabetic peripheral neuropathy based on random forest and logistic regression

ObjectiveThe primary objective of this study was to investigate the risk factors for diabetic peripheral neuropathy (DPN) and to establish an early diagnostic prediction model for its onset, based on clinical data and biochemical indices.MethodsRetrospective data were collected from 1,446 diabetic patients at the First Affiliated Hospital of Anhui University of Chinese Medicine and were split into training and internal validation sets in a 7:3 ratio. Additionally, 360 diabetic patients from the Second Affiliated Hospital were used as an external validation cohort. Feature selection was conducted within the training set, where univariate logistic regression identified variables with a p-value < 0.05, followed by backward elimination to construct the logistic regression model. Concurrently, the random forest algorithm was applied to the training set to identify the top 10 most important features, with hyperparameter optimization performed via grid search combined with cross-validation. Model performance was evaluated using ROC curves, decision curve analysis, and calibration curves. Model fit was assessed using the Hosmer-Lemeshow test, followed by Brier Score evaluation for the random forest model. Ten-fold cross-validation was employed for further validation, and SHAP analysis was conducted to enhance model interpretability.ResultsA nomogram model was developed using logistic regression with key features: limb numbness, limb pain, diabetic retinopathy, diabetic kidney disease, urinary protein, diastolic blood pressure, white blood cell count, HbA1c, and high-density lipoprotein cholesterol. The model achieved AUCs of 0.91, 0.88, and 0.88 for the training, validation, and test sets, respectively, with a mean AUC of 0.902 across 10-fold cross-validation. Hosmer-Lemeshow test results showed p-values of 0.595, 0.418, and 0.126 for the training, validation, and test sets, respectively. The random forest model demonstrated AUCs of 0.95, 0.88, and 0.88 for the training, validation, and test sets, respectively, with a mean AUC of 0.886 across 10-fold cross-validation. The Brier score indicates a good calibration level, with values of 0.104, 0.143, and 0.142 for the training, validation, and test sets, respectively.ConclusionThe developed nomogram exhibits promise as an effective tool for the diagnosis of diabetic peripheral neuropathy in clinical settings.