Diabetic peripheral neuropathy (DPN) affects nearly 50% of patients with diabetes mellitus, leading to impaired balance and falls. Vibrotactile stimulation during walking is shown to improve gait performance, although the effects of targeted stimulations in the swing phase of gait are unexplored. This study investigated the effects of swing-phase vibrotactile stimulation on gait parameters in DPN. We conducted a prospective controlled study with the DPN group (DG) aged 18-75 years diagnosed with DPN and the control group (CG) with no diagnosis of diabetes. Participants completed 3-minute walk and Timed Up and Go tests with and without vibrotactile stimulation provided by smart shoes. The shoes measured gait parameters, including stride length, velocity, strike angle, heel clearance, swing-stance ratio, stride duration, and distance. Analysis included the Mann-Whitney U test, with a significance threshold set at P <.05. A total of 28 individuals were analyzed (CG n = 18; DG: n = 10). DG participants were of higher age and BMI compared with controls (P < .01). At baseline, the DG demonstrated shorter stride length, smaller normalized stride length, lower walking velocity, reduced strike angle, and shorter distance covered in the 3-minute walk (P < .01). Between-group comparisons revealed increased heel clearance in controls (P = .03), which was attenuated after adjusting for age and BMI (P = .17). Our findings did not reveal an immediate effect of swing-phase stimulation on gait parameters in DPN patients. However, temporal gait parameters may require more demanding tasks or longer exposure to yield measurable benefits. Larger, age-matched trials using variability data are warranted to determine efficacy and identify responders in DPN. Level II, prospective comparative study.

PurposeTo explore the mechanism by which alpha-lipoic acid (ALA) regulates mitochondrial axonal transport to protect the sciatic nerve in diabetic rats.MethodsAmong 55 healthy male Sprague‒Dawley rats, 40 were randomly selected, fed a high-carbohydrate/high-fat diet and intraperitoneally injected with streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into diabetic peripheral neuropathy (DPN) and alpha lipoic acid (ALA) groups, with 15 rats in each group, excluding the rats in which diabetes failed to be induced and the dead rats. The other 15 rats were used as the control group. The rats in the ALA group were administered an ALA suspension (60 mg/kg/day) by gavage for 12 weeks. The rats in the control group and DPN group were gavaged with an equal volume of distilled water every day for 12 weeks. After the intervention was complete, the motor nerve conduction velocity (MNCV) and paw withdrawal threshold (PWT) were measured. Morphological changes in the sciatic nerve were observed by HE staining. Immunofluorescence staining and Western blotting were performed to measure protein expression levels. In vitro, a model of NSC34 cell injury was established by treating cells with high concentrations of glucose and palmitic acid sodium. NSC34 cells were randomly divided into the control group, DPN group and ALA group. The ALA group was treated with ALA for 24 hours. Changes in the axons of NSC34 cells were assessed by measuring the length of the axons. Immunofluorescence staining was performed to determine the fluorescence intensity of the cells, and Western blotting was performed to determine the grayscale value of each band.ResultsALA increased the MNCV and PWT in DPN rats and increased the levels of phosphorylated AMP-activated protein kinase (p-AMPK) and phosphorylated cAMP-response element-binding protein (p-CREB). The expression of a motor protein involved in anterograde axonal mitochondrial transport, kinesin family member 5A (KIF5A), was upregulated, whereas the expression of a dynein protein involved in mitochondrial retrograde transport, Dynein cytoplasmic 1 intermediate chain 2 (DYNC1I2), was downregulated by ALA.ConclusionThe results of this study suggest that ALA alleviates peripheral nerve injury in diabetic rats by promoting the anterograde axonal transport of mitochondria, which may be related to AMPK/CREB signaling.

Dissociated Magnetic Susceptibility and White Matter Microstructure in Type 2 Diabetes with Peripheral Neuropathy.

ObjectiveTo quantify circulating levels of C-C chemokine receptor-2 (CCR2) and indoleamine-2,3-dioxygenase-1 (IDO1) in patients with type 2 diabetes mellitus (T2DM) complicated by diabetic peripheral neuropathy (DPN) and to evaluate their potential as early biomarkers for DPN detection.MethodsIn this retrospective observational study, 367 patients with T2DM admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei between January 2021 and November 2024 were consecutively enrolled. Participants were stratified into a DPN group (n = 108) and a non-DPN group (n = 259) based on the presence or absence of DPN. Clinical baseline data were collected, and serum CCR2 and IDO1 levels were determined by enzyme-linked immunosorbent assays (ELISA). Their associations with DPN and predictive performance were evaluated using Spearman correlation, multivariate logistic regression, random-forest modeling, and receiver operating characteristic (ROC) curve analyses.ResultsMedian serum CCR2 (7.32 ng/mL) and IDO1 (9.77 ng/mL) concentrations were both significantly higher in the DPN cohort than in the non-DPN group (P < 0.05 for each) and were positively correlated (r = 0.384, P < 0.001). Multivariable logistic regression identified elevated CCR2 (OR 1.460, 95% CI 1.047–2.035) and IDO1 (OR 1.317, 95% CI 1.220–1.421) as independent risk factors for DPN. In a random forest model, CCR2 and IDO1 ranked as the third and fourth most important predictors, respectively. ROC analysis yielded areas under the curve (AUCs) of 0.728 for CCR2 and 0.749 for IDO1 individually; combining the two biomarkers increased the AUC to 0.786 (95% CI 0.729–0.844), with 62.0% sensitivity and 89.6% specificity.ConclusionSerum CCR2 and IDO1 are significantly up-regulated in patients with DPN and represent independent risk factors for its development. Their combined measurement enhances early detection accuracy, offering a clinically useful biomarker panel for DPN.

Background: A debilitating complication of diabetes is diabetic peripheral neuropathy (DPN), for which effective therapy remains limited. In this research, we evaluated the effects of quercetin, pioglitazone, insulin, and a novel thiazolidine-2,4-dione derivative (TZDd) on the nerve functions in a streptozotocin (STZ)-induced rat model of DPN. Methods: In the experimental groups, STZ (60 mg/kg) was administered to Wistar rats to induce type 1 diabetic neuropathy, and the control and experimental DPN groups were treated with quercetin, pioglitazone, insulin, or TZDd for 5 weeks. The sensory and motor symptoms of DPN were evaluated via behavioral tests, nerve conduction velocity measurements, and electrophysiological assessment, and the synthesized TZDd was evaluated in silico for its pharmacokinetic, toxicological, and drug-likeness properties. Results: The diabetic rats developed DPN after 2 weeks of STZ administration, as evidenced by the significant reduction in the sensory and motor nerve conduction velocities (SNCVs and MNCVs) and increased mechanical hyperalgesia; on the other hand, quercetin, pioglitazone, insulin, and TZDd administration ameliorated the nerve functions of the DPN rats. In the in silico predictions, the novel TZDd exhibited no toxicity risks and demonstrated drug-like properties. Conclusions: Quercetin, pioglitazone, insulin, and TZDd showed neuroprotective effects that enhanced functional recovery in experimental DPN. These findings highlight that TZDd may represent a valuable compound with neuroprotective effects that could be used in DPN therapy and management.

The morphological alterations of the tibial nerve in patients with diabetes mellitus, both with and without diabetic peripheral neuropathy (DPN), are challenging to differentiate using B-mode ultrasound. In this study, we assessed the stiffness changes of the tibial nerve by 2-dimensional shear-wave elastography (2D-SWE). We gathered data from 70 adults with valid 2D-SWE measurements, comprising 25 individuals in DPN Group A who were diagnosed with DPN and had peripheral nerve symptoms in the past 6 months, 15 individuals in DPN Group B who were diagnosed with DPN but had no peripheral nerve symptoms in the past 6 months, 16 individuals with type 2 diabetes but without DPN, and 14 healthy individuals. The maximal thickness, cross-sectional area, and stiffness of the tibial nerve among groups were analyzed. DPN Group A had higher tibial nerve stiffness than Group B, non-DPN, and control groups (p < .05). The area under the curve (AUC) for 2D-SWE parameters in detecting increased nerve stiffness was 0.956 for G1 (mean stiffness) and 0.979 for G3 (distal stiffness), respectively, with optimal cut-off values of 20.01 and 28.41 kPa. 2D-SWE is a promising non-invasive technique for early diagnosis of DPN, effectively reflecting changes in nerve stiffness associated with the condition. This method may enhance clinical interventions aimed at preventing disease progression.

Diabetic peripheral neuropathy (DPN) is a major complication of type 2 diabetes mellitus (T2D) that reduces quality of life and increases the risk of foot ulcers and amputations. Early detection is essential, and blood-based biomarkers may support improved screening and timely intervention. This study aimed to identify novel circulating biomarkers for the identification of DPN in patients with T2D. In the screening phase, plasma samples from 43 participants (10 healthy volunteers [HV], 20 T2D without complications, and 13 T2D with DPN) were analyzed using an antibody array targeting 310 proteins. Thirteen differentially expressed proteins were identified, and six hub proteins were selected through bioinformatic analysis. In the validation phase, plasma concentrations of the six proteins were measured by ELISA in 252 subjects (100 HV, 97 T2D without complications, and 55 T2D with DPN). Mucin-1 expression in sciatic nerves was further evaluated in db/db mice. Of the six hub proteins (TGFB1, MUC1, PF4, IL2RA, SELL, B2M), only mucin-1 showed a significant increase in the DPN group. Plasma mucin-1 positively correlated with MNSI scores and negatively with motor and sensory nerve conduction velocities. In db/db mice, sciatic nerve mucin-1 expression was elevated, while CD31 expression was reduced. Plasma mucin-1 is strongly associated with DPN in both humans and animals and may serve as a promising biomarker for the screening and early identification of DPN.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus, and is often underdiagnosed because of its variable clinical presentation and operator-dependent diagnostic tools. Shear wave elastography (SWE), which quantitatively evaluates tissue stiffness, has the potential to enhance conventional ultrasound by improving diagnostic accuracy and consistency. Nevertheless, a comprehensive analysis examining the extent to which the integration of SWE with conventional ultrasound can enhance the diagnostic performance of radiologists across varying levels of expertise has yet to be performed. In this study, a total of 458 lower extremities from patients with type 2 diabetes were examined via ultrasound and SWE. Four radiologists (two seniors and two juniors) independently assessed the grayscale ultrasound, SWE, and combined images. Diagnostic performance was compared via receiver operating characteristic (ROC) curves and sensitivity and specificity metrics. SWE measurements revealed significantly greater stiffness of the tibial nerve in the DPN group than in the non-DPN group, with values of 37.30kPa versus 25.40kPa (P < 0.001) and corresponding shear wave velocities of 3.54m/s versus 2.90m/s (P < 0.001). The combined images improved diagnostic accuracy across all readers. Notably, junior radiologists exhibited a substantial improvement in terms of sensitivity (ΔSensitivity = 25.565, 95% CI: 18.477-32.653, P = 0.004). In contrast, for the senior radiologists, neither the sensitivity nor the specificity significantly increased with increasing integration SWE. Combining SWE with conventional ultrasound improves the diagnostic accuracy for DPN and helps reduce performance gaps between junior and senior radiologists. SWE may serve as an effective adjunct to support early detection and consistent evaluation of DPN in clinical practice.

Objective: Diabetic peripheral neuropathy (DPN) is a common chronic complication in older adults with type 2 diabetes mellitus (T2DM). Early diagnosis is essential for delaying disease progression. This study set out to explore the predictive value of the combined detection of serum adipocytokine adipsin and 25-hydroxyvitamin D [25(OH)D] in elderly DPN patients, and to provide new strategies for early intervention. Methods: Based on the electronic medical records of our hospital from January 2024 to June 2025, 150 elderly patients with T2DM (104 in DPN group and 57 in non-DPN group) were enrolled. Serum adipsin was detected by ELISA, and 25(OH)D was measured via chemiluminescent immunoassay. The diagnostic efficacy of the combined detection was confirmed by univariate analysis, Logistic regression model, and ROC curves. Disease course and age-stratified subgroup analyses were further carried out. Results: DPN patients showed higher serum adipsin but lower 25(OH)D levels than non-DPN cases (P&lt;0.05). Adipsin + 25(OH)D detection exhibited an AUC of 0.831 (sensitivity: 64.42%, specificity: 87.72%), higher than single-index predictions. Subgroup analysis indicated superior prediction efficiency of the combined detection in patients with a course of disease ≥6 years (AUC&gt;0.85). According to correlation analysis, adipsin was positively correlated with FPG, HbA1c, and VPT, and negatively correlated with NCV and SCV; while the opposite was true for 25(OH)D. Conclusion: Serum adipsin combined with 25(OH)D has high predictive value for elderly DPN, and their synergistic effect may be exerted through the "inflammation-oxidative stress-metabolic disorder" axis.

Aim: To evaluate the association between liver fibrosis, investigated by non-invasive fibrosis scores and measurement of stiffness, and diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM). Methods: We conducted a cross-sectional, retrospective study including individuals with T2DM and hepatic steatosis who underwent a DPN examination. Liver fibrosis risk was estimated using the fibrosis-4 score (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), aspartate transaminase (AST)/alanine transaminase (ALT) ratio, and the AST to platelet ratio index. Fibrosis was investigated using the vibration-controlled transient elastography (Fibroscan®) in a subgroup of patients. Liver stiffness measurement (LSM) ≥ 7.0 kPa defined significant fibrosis. Results: Eighty-six T2DM subjects (mean age 59.22 ± 13.18 years; 69.8% male; DPN prevalence 43%) were included. Higher risk scores of liver fibrosis (FIB-4 and AST/ALT) in subjects with DPN compared to those without DPN were detected (FIB-4: 1.23 ± 0.66 vs. 1.63 ± 0.85; P = 0.018; AST/ALT: 0.89 ± 0.23 vs. 1.11 ± 0.61; P = 0.026). The DPN group showed higher LSM values, and the Michigan Diabetic Neuropathy Score was directly related to LSM (Rho: 0.304, P = 0.026). Moreover, a higher prevalence of alteration in vibration or reflexes was observed in subjects with LSM ≥ 7 kPa (P = 0.025 and P = 0.042, respectively). Finally, the evaluation of vibration or reflexes in individuals at high risk of liver fibrosis at FIB-4 and AST/ALT was associated with DPN (FIB-4 + abnormal vibration: P = 0.047; FIB-4 + abnormal reflexes: P = 0.013; AST/ALT + abnormal vibration: P &lt; 0.001; AST/ALT + abnormal reflexes: P &lt; 0.001). Conclusion: The evaluation of vibration or reflexes would be useful in identifying DPN in T2DM with Metabolic Dysfunction-Associated Steatotic Liver Disease at high risk of fibrotic evolution.

As corneal dendritic cells (DCs) are immune cells that can reflect systemic inflammatory activity, this study aimed to investigate whether the density and maturity of corneal DCs are associated with diabetes, diabetic peripheral neuropathy (DPN), and neuropathic pain. Participants included individuals with type 1 diabetes mellitus (T1DM) and painful DPN (n = 19), T1DM and painless DPN (n = 15), T1DM without DPN (n = 19), and healthy controls (n = 20). Corneal confocal microscopy was used to quantify and categorize DCs as either mature or immature and based on their proximity to corneal nerves. No significant differences between groups were observed in total DC density (p = 0.34). Subgroup analysis revealed distinct patterns in which participants with DPN (regardless of pain status) exhibited a higher density of immature DCs distant from corneal nerves compared to those without DPN (14.4 [6.64-37.5] vs. 3.75 [0-17.7] no./mm2, p < 0.05). Healthy controls had a greater density of immature DCs near the nerves compared to the T1DM + DPN group (2.8 [0-8.44] vs. 8.3 [3.12-15.1] no./mm2), while the T1DM + DPN group had a higher density than the painful DPN (3.1 [1.25-5.62] no./mm2). For mature DCs near the nerves, individuals with painful DPN (2.5 [1.4-3.12] no./mm2) had a lower density compared to all other groups. This study demonstrates distinct patterns of corneal DC distribution in relation to painful and painless DPN. The findings suggest that immune-mediated mechanisms may play a role in the development of neuropathy and neuropathic pain in diabetes. The pathophysiological significance remains to be clarified. ClinicalTrials.gov: NCT04078516.

Cerebral alterations are associated with diabetic peripheral neuropathy (DPN) and neuropathic pain, including reductions in brain volumes, cortical thickness, sulcus depth, and alterations in metabolites and functional connectivity. This study combined multimodal magnetic resonance imaging (MRI) data to differentiate clinical phenotypes and uncover distinct associated brain features using machine-learning based classification. Seventy-six participants were recruited: 20 healthy and 56 with type 1 diabetes mellitus: 18 without DPN, 19 with painless DPN, and 19 with painful DPN. Three machine learning classifiers were evaluated, including accompanying feature importance from the highest performing classifier. Class membership probabilities (predicted probability of belonging to a group) were compared across classes and correlated with clinical measures of pain and nerve function for the class concerned. Accuracies were≥0.75 for all classes except painless DPN, though separated by painful membership probability (p≤0.02). Overall classification accuracy was 0.71. The most informative features were functional connectivity, followed by N-acetylaspartate/creatine and sulcal depth. The painful DPN group was separated from the remaining groups by painful membership probability (p≤0.01), which correlated with pain measures. Diabetes without DPN membership probability correlated with sural nerve conduction (p≤0.001, rs≥0.49) and warm detection thresholds (p≤0.001, rs=-0.51). This exploratory study suggests that different MRI modalities provide complementary information describing phenotypes of diabetes, DPN and DPN related pain, with functional connectivity being most essential. Thus, implying a multifactorial cerebral manifestation of neuropathy and pain in diabetes and aiding the development of grading and prognostic tools for personalised treatments. Studies of larger cohorts should validate these findings.

The aim of this study is to ascertain the role of high-resolution nerve ultrasound (NUS) and shear wave elastography (SWE) in assessing the stratified diagnosis of diabetic peripheral neuropathy (DPN). To assess the potential diagnostic worth of NUS and SWE, across different levels of DPN. To determine whether the integration of NUS with SWE can enhance diagnostic accuracy. This retrospective study enrolled a total of 121 patients diagnosed with type 2 diabetes mellitus from September 2022 to May 2024, including 91 patients with DPN. All participants were categorized into 4 groups: group A (subclinical-DPN), group B (suspected-DPN), group C (clinically diagnosed-DPN), group D (confirmed-DPN), with a control group of type 2 diabetes mellitus patients without DPN. NUS and SWE examinations were performed to generate the receiver operating characteristics (ROC) curves of different diagnostic methods, determine the diagnostic threshold and compare the difference in diagnostic efficacy. Significant differences were observed in tibial nerve characteristics between DPN patients and controls. The DPN group had a larger cross-sectional area (CSA; 24.78 ± 4.75 mm² vs 22.40 ± 3.19 mm², P < .05) and higher mean elasticity modulus (Emean; 54.46 ± 16.76 kPa vs 34.37 ± 9.37 kPa, P < .05). ROC curve analysis was performed to evaluate the diagnostic performance of CSA, Emean, and combined model (Emean + CSA) in detecting DPN. The area under the ROC curve of Emean was significantly higher than NUS (z = −4.032, P < .001). The combined model showed no significant improvement over SWE alone (z = −1.486, P = .137). Stratified analysis revealed that CSA measurements are more reliable in advanced disease stages; Emean demonstrated significantly superior diagnostic efficacy compared to CSA for all disease stages. The combination of Emean and CSA showed more pronounced improvements in all disease stages compared to CSA alone, while only showing marginal improvement trends in subclinical and confirmed-DPN, without reaching statistical significance compared to Emean. This study establishes an evidence-based, stage-specific framework for the diagnosis of DPN. The combined NUS + SWE approach offers unparalleled advantages for early detection, whereas SWE alone may suffice in advanced stages.

Diabetic foot ulcers (DFUs) and diabetic peripheral neuropathy (DPN) are severe complications in type 2 diabetes mellitus (T2DM). Selenium (Se) is an important element with antioxidant properties, which is crucial for human homeostasis. In this narrative mini review, we summarise the evidence on the potential association of Se with DPN and DFUs. Generally, in most of the limited number of studies, serum Se levels were significantly lower in subjects with DPN or DFUs. In addition, one study demonstrated that urinary Se levels were lower in the DPN group. Nevertheless, further investigations are needed to confirm these preliminary findings.

UFP-101 alleviates diabetic peripheral neuropathy through membrane metallo-endopeptidase.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM), associated with chronic hyperglycemia, insulin resistance, and neuroinflammation. Despite the widespread use of Michigan Neuropathy Screening Instrument (MNSI) for early identification in neuropathy screening, studies assessing its relationship between NGF, insulin resistance, and neuropathy in T2DM patients, particularly in Indonesia, remain limited. Therefore, this study was conducted to evaluate associations between serum NGF, insulin resistance, β-cell function, and MNSI scores in T2DM.METHODS: Seventy-seven T2DM subjects were classified into DPN and non-DPN groups using MNSI. Subjects were excluded if they have comorbidities and conditions potentially affecting metabolic, immune, or organ function. Enzyme-linked immunosorbent assay (ELISA) was used for the measurement of serum NGF, enzymatic hexokinase method for fasting plasma glucose (FPG) and 2-hour postprandial glucose (2HPP), high-performance liquid chromatography (HPLC) for glycated hemoglobin (HbA1c), and chemiluminescent immunoassay for fasting insulin. Homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were then calculated.RESULTS: Most of the study subjects had NGF level of &lt;11 pg/mL. NGF concentrations showed inverse correlations with HOMA-IR (r=–0.263, p=0.021) and HOMA-β (r=–0.316, p=0.005). In the DPN subgroup, NGF demonstrated a stronger negative correlation with HOMA-β (r=–0.425, p=0.009), whereas no significant correlation was found in non-DPN. HbA1c was higher in DPN (p=0.014). No significant associations were observed between NGF and HbA1c, FPG, or 2HPP. NGF was significantly associated with MNSI Part B scores (p=0.032), reflecting objective neuropathic findings, but not with MNSI Part A or total scores.CONCLUSION: Lower NGF levels were significantly associated with insulin resistance and β-cell dysfunction in T2DM. The association with MNSI part B suggests that physical examination findings may reflect NGF-related neuropathic alterations better than symptom-based assessments.KEYWORDS: diabetic peripheral neuropathy, HOMA-IR, HOMA-β, Michigan Neuropathy Screening Instrument, nerve growth factor, T2DM

ObjectiveTo evaluate the diagnostic potential of viscosity (Vi) imaging and shear wave elastography (SWE) of the tibial nerve in diabetic peripheral neuropathy (DPN).Materials and MethodsThis prospective study enrolled 40 patients with type II diabetes mellitus (T2DM) accompanied by DPN, 40 T2DM patients without DPN, and 40 healthy controls between January 2025 and April 2025. The bilateral tibial nerves were examined using SWE and Vi imaging to measure shear wave speed (Cs, m/s) and Vi (Pa·s). The reference standards for the DPN diagnosis comprised clinical examination, electromyography, and quantitative sensory testing. Diagnostic performance was assessed using receiver operating characteristic curve analysis and by calculating sensitivity and specificity at the optimal cutoff values for Cs and Vi. The areas under the curve (AUCs) were compared using DeLong’s test.ResultsOn the right side, the DPN group exhibited significantly higher Csmean (median: 4.05 m/s [interquartile range: 3.30–4.51] vs. 3.25 m/s [2.95–3.45]; P < 0.05) and Vimean (median: 3.51 Pa·s [2.70–4.58] vs. 2.43 Pa·s [2.20–2.97]; P < 0.05) compared to the non-DPN group, with similar trends observed on the left side. Both Csmean (AUC = 0.826 [95% confidence interval: 0.725–0.902]) and Vimean (AUC = 0.765 [0.657–0.852]) demonstrated favorable diagnostic performance for DPN, without a significant difference (P = 0.144). Combining Csmean and Vimean resulted in a sensitivity of 62.5% (25/40), a specificity of 95.0% (38/40), and an AUC of 0.828 (0.727–0.903), without significant improvement compared to Csmean or Vimean alone (P = 0.573 and 0.148, respectively).ConclusionVi imaging quantifies nerve Vi in DPN and offers a novel, non-invasive diagnostic approach to distinguish patients with DPN from those without the condition. However, viscoelastic imaging does not provide greater diagnostic value than SWE.

Abstract Background Diabetic peripheral neuropathy (DPN) has emerged as one of the most potent predictors of decreased quality of life in type 2 diabetes (T2D) patients. Early detection is essential for avoiding or delaying DPN hazards. Early neural damage is typically misdiagnosed by nerve electrophysiological tests. Thus, there is an increased need for simple and specific biomarkers for nerve damage that reflect early DPN. Phosphorylated neurofilament-heavy chain protein (pNF-H) is the main structure of neural axons that is released from axons into the blood upon axonal injury, making it a biomarker of axonal damage. Aim To study the application of serum pNF-H level as a biomarker for DPN in patients with T2D. Patients and methods Ninety age, gender, and body mass index-matched participants were recruited. The study included 35 T2D patients with DPN (DPN group), 35 T2D patients without DPN (non-DPN group), and 20 nondiabetic healthy individuals (control group). DPN was assessed by Neurological Symptomology Score (NSS), modified Neuropathy Disability Score (NDS), neurothesiometer, and 10-g monofilament. Clinical data and laboratory parameters were collected. Serum pNF-H levels were measured via ELISA. Results pNF-H serum levels were significantly higher in both diabetic groups versus the control group (p &lt; 0.001) and in the DPN group than in those without neuropathy (p &lt; 0.001). HbA1c, NSS, and NDS were positively correlated with pNF-H in the DPN group (p = 0.01, &lt; 0.001, and &lt; 0.001, respectively). Age, diabetes duration, BMI, low-density lipoprotein, fasting plasma glucose, NSS, and NDS were positively correlated with pNF-H in the non-DPN group (p = 0.003, 0.024, 0.041, 0.013, 0.011, &lt; 0.001, and &lt; 0.001, respectively). pNF-H was independently correlated with DPN. The cutoff value of serum pNF-H above which diabetic subjects were likely to develop DPN was 33.45 ng/dl. Conclusion Serum pNF-H levels are significantly higher in diabetic subjects, specifically those with peripheral neuropathy. pNF-H could be a potential biomarker of DPN in patients with T2D.

Introduction. Type 2 diabetes mellitus (T2DM) is the leading metabolic disease in Indonesia. Diabetic peripheral neuropathy (DPN), a major complication of T2DM, was associated with insulin resistance and adipose dysfunction. Visceral adiposity index (VAI) is a tool to measure visceral fat as the indicator of adipose dysfunction and insulin sensitivity. The association between VAI and DPN has not been widely researched, especially in Indonesia. This study aims to assess the association between them. Methods. This was a cross-sectional study conducted on adult patients (aged ≥18 years) with T2DM at H. Adam Malik General Hospital, Medan, from December 2024 to March 2025. DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI), consisting of a questionnaire (MNSI A) and physical examination (MNSI B). VAI was calculated using waist circumference, body mass index (BMI), triglyceride level, and high-density lipoprotein (HDL) cholesterol level. A bivariate analysis was conducted to compare mean VAI values between patients with and without DPN and to assess correlations between VAI and MNSI scores. Results. From a total of 80 subjects, the average age was 56 years (SD 9), and the majority were female (56.3%). The median VAI value in the DPN group was 2.863 (0.401–11.665), slightly higher than in the non-DPN group, which was 2.549 (0.781–17.414), but the difference was not statistically significant (p=0.34). No statistically significant correlation was found between VAI and MNSI A score (r=0.092; p=0.42) or MNSI B score (r=0.12; p=0.31). Conclusion. There was no significant association between VAI and DPN in patients with T2DM.

ObjectivesEvidence suggests a link between gut microbiota and diabetes mellitus, yet the specific role in diabetic peripheral neuropathy (DPN) remains elusive. The study aims to explore the association through Mendelian randomization and 16S rRNA gene sequencing analysis.Materials and methodsMendelian randomization (MR) analysis was employed to investigate the causal association between gut microbiota and diabetic neuropathy. Diabetes mellitus (DM) and DPN mice models were developed via high-fat diet (HFD) feeding followed by intraperitoneal streptozotocin (STZ) administration at 30 mg/kg (DM group) or 60 mg/kg (DPN group). The occurrence of diabetic neuropathy was determined by evaluating pain-related behavioral parameters in mice. Additionally, fecal samples from mice and patients with diabetic neuropathy were collected, and 16S rRNA sequencing was performed to analyze the composition of gut microbiota.ResultsMendelian randomization analysis identified 14 gut microbiota species exhibiting a causal relationship with diabetic neuropathy. In animal studies, diabetic neuropathy mice exhibited decreased mechanical pain thresholds and reduced thermal withdrawal latency. Sequencing analyses further revealed significant alterations in gut microbiota composition in both DPN mice and DPN patients compared to control group.ConclusionThis study integrates Mendelian randomization analysis with 16S rRNA fecal assessments from animal models and clinical patients, revealing that gut microbiota imbalances may contribute to diabetic neuropathy development and providing novel insights for its prevention and therapeutic strategies.