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Background: Diabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM., Methods: In this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls., Results: The prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire's cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients., Conclusions: Despite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies., (© 2024. The Author(s).)

Purpose: To explore variations in systemic and ocular parameters among patients with diabetes, both with and without diabetic peripheral neuropathy (DPN) and to identify sensitive indicators for DPN diagnosis., Methods: Ninty-five patients with type 2 diabetes mellitus (T2DM) were involved in this cross-sectional study, including 49 without DPN and 46 with DPN. Ocular parameters were obtained using optical coherence tomography angiography (OCTA) and corneal confocal microscopy (CCM)., Result: Patients with DPN presented with significantly higher HbA1c (p < 0.05) and glycated albumin (GA, p < 0.01) levels, increased prevalence of diabetic retinopathy (DR, p < 0.05), and lower serum albumin (ALB, p < 0.01) and red blood cell (RBC, p < 0.05) levels. Ocular assessments revealed reduced corneal nerve fiber length (CNFL, p < 0.001) and enlarged foveal avascular zone (FAZ) area (p < 0.05) in DPN group. Logistic regression analysis indicated a significant association of presence of DR, RBC, GA, ALB, CNFL and DPN (p < 0.05, respectively). In the binary logistic regression for DPN risk, all three models including the presence of DR and CNFL exhibited the area under the curve (AUC) exceeding 0.8., Conclusion: The study establishes a strong correlation between ocular parameters and DPN, highlighting CCM's role in early diagnosis. Combining systemic and ocular indicators improves DPN risk assessment and early management., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Diabetic peripheral neuropathy (DPN) frequently occurs as a secondary condition in individuals with type 2 diabetes mellitus (T2DM)., Objective: To explore the relationship of lncRNA FTX and miR-186-5p levels with DPN in T2DM., Methods: The study enrolled 50 patients with T2DM and 45 patients with DPN. Expression levels of FTX and miR-186-5p were measured by RT-qPCR. The levels of MDA, GSH, and SOD in the serum were measured to assess the patients' oxidative stress levels. In addition, the target genes of miR-186-5p were analyzed by bioinformatics., Results: Serum FTX levels were increased and miR-186-5p levels were decreased in patients with T2DM and DPN. Both of them had high diagnostic value for T2DM and DPN. In addition, FTX and miR-186-5p were risk factors for the onset of DPN in people with T2DM and were significantly correlated with oxidative stress indicators in patients., Conclusion: FTX and miR-186-5p are closely related to the disease progression of DPN in people with T2DM and may become therapeutic targets for DPN in people with T2DM., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Oxidative stress is a risk factor for distal sensorimotor polyneuropathy (DSPN). Selenoprotein P is a protein with antioxidant properties but has not been investigated in the context of DSPN. This study aimed to assess the associations between selenoprotein P and DSPN in people without and with type 2 diabetes (T2D)., Methods: Cross-sectional and prospective analyses were based on 1053 (including 217 with T2D) and 513 participants (including 79 with T2D), respectively, aged 61-82 years from the population-based KORA F4 survey. DSPN at baseline (KORA F4) and in the follow-up survey KORA FF4 was defined based on the Michigan Neuropathy Screening Instrument. Serum levels of full-length selenoprotein P were quantified by ELISA. Associations between selenoprotein P and prevalent or incident DSPN were estimated using logistic regression analysis adjusting for multiple confounders., Results: Selenoprotein P levels were not associated with prevalent DSPN in the total sample. However, there was a significant interaction by diabetes status. Higher levels of selenoprotein P were associated with lower odds of prevalent DSPN in individuals without T2D (fully adjusted model: OR 0.825 [95 % CI 0.682, 0.998], p = 0.0476), but not in those with T2D (OR [95 % CI] 1.098 [0.829, 1.454], p = 0.5132; p interaction  = 0.0488). Selenoprotein P levels were not associated with incident DSPN over a follow-up of 6.5 years., Conclusion: In individuals without T2D from the older general population, lower selenoprotein P levels were associated with a higher prevalence of DSPN. Whether the antioxidant properties of selenoprotein P are responsible for the observed associations remains to be elucidated in future research., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest in connection with this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) is associated with increased risk of morbidity and premature mortality due to its various complications. In an Indian study, the prevalence of diabetic peripheral neuropathy (DPN) in type 2 diabetic subjects was shown to be 29.2%. There is increasing evidence that a deficiency of nerve growth factor (NGF) in diabetes, as well as the calcitonin gene-related peptide (CGRP), may also contribute to the development of DPN. The aim of the current study was to evaluate nerve growth factor levels with neuropathy in type 2 DM., Materials and Methods: Forty healthy controls and 40 patients with type 2 DM were recruited; they were asked to report to Dept. of Physiology for initial history taking, general examination and neuropathy examination. A total of 5 mL of blood was collected for neurotrophic factor estimation as well as glycemic profile estimation., Results: The brain-derived neurotrophic factor (BDNF) values were significantly lower in the DM group whereas the insulin levels were also quite high in DM. The hot thresholds for both the upper limb and lower limb were greater in the DM group suggesting the impending neuropathy. Similarly, the Michigan scores were also greater in the DM group. The neuropathy parameters especially the Michigan A and B and the hot thresholds were positively correlated with duration of DM and glucose profile., Conclusion: The neurotrophic factors especially BDNF are drastically reduced in DM patients and are negatively associated with neuropathy, and hence, BDNF can be utilized as a therapeutic target to treat and prevent neuropathy., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

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., (© 2024. The Author(s).)

Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes., (© 2024. The Author(s).)

In various diseases characterized by inflammation, the C-reactive protein to albumin ratio (CAR) serves as a marker of inflammation. Type 2 diabetes mellitus (T2DM) is frequently complicated by diabetic neuropathy (DN) and timely diagnosis is crucial for treatment and potential reversal of this complication. Since both DN and T2DM are associated with chronic, low-grade inflammation, our study aimed to evaluate CAR levels in type 2 diabetic subjects with DN and compare them to those in subjects without DN. Patients presenting to our institutional outpatient clinics were divided into two groups based on the presence of DN. Data on characteristics and laboratory measures, including CAR,were compared between the DN and non-DN groups. The median CAR in the DN and non-DN groups was 2.19% (range 0.2%-49%) and 0.56% (range 0.02%-5.8%), respectively (P < 0.001). CAR showed significant positive correlations with weight (r = 0.19, P = 0.01), body mass index (BMI) (r = 0.11, P = 0.03), waist circumference (r = 0.10, P = 0.046), fasting glucose (r = 0.14, P = 0.004), serum creatinine (r = 0.25, P < 0.001), triglyceride (r = 0.17, P < 0.001), and LDL-cholesterol (r = 0.13, P = 0.001) levels, and an inverse correlation with estimated glomerular filtration rate (eGFR) (r = -0.16, P < 0.001). Additionally, CAR demonstrated a sensitivity of 78% and specificity of 73% for predicting DN at a threshold of 1.02% (area under curve [AUC] 0.84, 95% confidence interval [CI] 0.82-0.87, P < 0.001). High CAR levels were independently associated with an increased risk of DN (odds ratio [OR] 1.34, 95% CI 1.08-1.62, P < 0.001). Elevated CAR levels may thus be considered a potential marker for DN in T2DM patients.

Background: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN., Methods: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves., Results: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated., Conclusions: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Aims/introduction: To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin-like growth factor-1 (IGF-1) and DPN in individuals with type 2 diabetes., Materials and Methods: A total of 790 patients with type 2 diabetes participated in a cross-sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non-DPN). Blood samples were taken to measure IGF-1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing., Results: Patients with DPN exhibited significantly lower levels of IGF-1 compared with non-DPN patients (P < 0.001). IGF-1 was positively correlated with the average amplitude of both motor (P < 0.05) and sensory nerves (P < 0.05), but negatively correlated with the vibration perception threshold (P < 0.05). No significant difference was observed between IGF-1 and nerve conduction velocity (P > 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA 1c , and the low levels of IGF-1 as independent risk factors (P < 0.001). Receiver operating characteristic analysis determined that at 8 years duration of diabetes, 8.5% (69.4 mmol/mol) HbA 1c and 120 ng/mL IGF-1, the optimal cut-off points, indicated DPN (P < 0.001)., Conclusions: A reduction of IGF-1 in patients with DPN suggests a potential protective role against axon injury in large fiber nerves of type 2 diabetes patients., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Previous studies have revealed that thyroid hormone (TH) levels are associated with the risk of diabetic peripheral neuropathy (DPN) in euthyroid patients with type 2 diabetes mellitus (T2DM). However, the relationship between TH sensitivity, a complementary method for assessing thyroid function, and DPN remains unclear. This study aimed to investigate the correlation between DPN and TH sensitivity in euthyroid patients with T2DM. Exactly 708 euthyroid adults with T2DM were retrospectively enrolled. The FT3/FT4 ratio was used to estimate peripheral TH sensitivity. Central TH sensitivity was assessed using the Thyrotroph T4 Resistance Index (TT4RI), Thyroid-Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). DPN was assessed using neurologic symptoms, signs, and nerve conduction velocity tests. The relationship between DPN and TH sensitivity was examined using logistic regression analysis. We observed that an elevated FT3/FT4 ratio was associated with DPN (OR = 1.36, 95%CI: 1.13-1.63, p = 0.0012). For each standard deviation (SD) increase in the TT4RI, TSHI, TFQI, and PTFQI, the OR of DPN was 0.80 (95%CI: 0.68-0.94, p = 0.0078), 0.72 (95%CI: 0.60-0.86, p = 0.0002), 0.69 (95%CI: 0.58-0.83, p < 0.0001), and 0.69 (95%CI: 0.58-0.82, p < 0.0001), respectively. These results suggested that reduced central and peripheral TH sensitivity is associated with a decreased risk of developing DPN., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the association of fasting C-peptide and glucagon with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2DM)., Methods: A comprehensive evaluation was conducted on 797 patients with T2DM to assess the various risk factors affecting DPN. The subjects were categorized into short duration and long duration group according to the duration of diabetes with a threshold of 10 years. Logistic regression analysis was employed to examine the association between DPN and islet function, as well as other parameters. Receiver operating characteristic curve analysis was performed to evaluate the predictive capability of glucagon., Results: The fasting C-peptide levels were significantly lower in the DPN patients with short duration of diabetes, but lost significance in the long duration group. Conversely, a decreased level of glucagon was only observed in DPN patients with long duration of diabetes. For the group with long duration of diabetes, glucagon was the sole risk factor associated with DPN. The receiver operating characteristic curve analysis revealed that glucagon in the long duration group exhibited a moderate area under the curve of 0.706., Conclusions: The serum glucagon levels in T2DM patients with DPN exhibited bidirectional changes based on the duration of diabetes. Decreased glucagon was associated with DPN in T2DM patients with long duration of diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine how plasma fibrinogen levels impact the severity of microvascular complications in people with type 2 diabetes while focussing on the molecular mechanisms of fibrinogen's role in such complications., Methods: The analytical, cross-sectional study was conducted from September 2022 to March 2023 at the Department of Medicine, Mardan Medical Complex and Teaching Hospital, Khyber Pakhtunkhwa, Pakistan, and comprised adult patients of either gender who had been diagnosed with type 2 diabetes and microvascular complications. Each patient was subjected to an evaluation of microvascular complications, including diabetic retinopathy, nephropathy and neuropathy, using validated diagnostic criteria and clinical examinations. Data was analysed using SPSS 26., Results: Of the 174 patients 97(%) were males and 77(%) were females. Retinopathy was found in 57(32.7) patients with median age 53 years (interquartile range: 46-63 years). Nephropathy was found in 55(31.6%) subjects with median age 54 years (interquartile range: 50-61 years). Neuropathy was found in 62(35.6%) patients with median age 53 years (interquartile range: 48-58 years). Diabetic neuropathy was significantly associated with elevated plasma fibrinogen levels and various biomarkers, such as creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05). Diabetic retinopathy was significantly linked with higher levels of fibrinogen, which manifested through symptoms, like floaters or dark spots, impaired colour vision, difficulty seeing at night, blurred or fluctuating vision and vision loss (p<0.05). Diabetic nephropathy and the progression of its severity was significantly associated with increased fibrinogen levels, as well as markers, like albuminuria, creatinine, urea, fasting blood glucose, glycated haemoglobin and estimated average glucose (p<0.05)., Conclusions: Elevated plasma fibrinogen levels in patients with type 2 diabetes significantly correlated with increased microvascular complications, underscoring the importance of monitoring and managing fibrinogen levels to mitigate diabetes-associated vascular pathologies.

Aims/introduction: Although several studies have shown the association between continuous glucose monitoring (CGM)-derived glycemic variability (GV) and diabetic peripheral neuropathy, no studies have focused on outpatients or used NC-stat®/DPNCheck™, a new point-of-care device for nerve conduction study (NCS). We investigated the association between CGM-derived GV and NCS using DPNCheck™ in outpatients with type 2 diabetes, and further analyzed the difference in results between patients with and without well-controlled HbA1c levels., Materials and Methods: All outpatients with type 2 diabetes using the CGM device (FreeStyle Libre Pro®) between 2017 and 2022 were investigated. Sural nerve conduction was evaluated by sensory nerve action potential (SNAP) amplitude and sensory conduction velocity (SCV) using DPNCheck™. Associations of CGM-derived GV metrics with SNAP amplitude and SCV were investigated., Results: In total, 304 outpatients with type 2 diabetes were included. In a linear regression model, most CGM-derived GV metrics except for the mean amplitude of glucose excursion and low blood glucose index were significantly associated with SCV, but not with SNAP amplitude. The significant associations of most CGM-derived GV metrics with SCV remained after adjustment for possible confounding factors, but not after adjustment for glycated hemoglobin (HbA1c). Most CGM-derived GV metrics were significantly associated with SCV after adjustment for HbA1c in patients with a HbA1c ≤ 6.9%, but not in those with a HbA1c ≥ 7.0%., Conclusions: In outpatients with type 2 diabetes, multiple CGM-derived GV metrics were significantly associated with SCV obtained by DPNCheck™. GV may have independent impacts on peripheral nerve function, particularly in patients with well-controlled HbA1c levels., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims: To assess if advanced characterization of serum glycoprotein and lipoprotein profile, measured by proton nuclear magnetic resonance spectroscopy ( 1 H-NMRS) improves a predictive clinical model of cardioautonomic neuropathy (CAN) in subjects with type 1 diabetes (T1D)., Methods: Cross-sectional study (ClinicalTrials.gov Identifier: NCT04950634). CAN was diagnosed using Ewing's score. Advanced characterization of macromolecular complexes including glycoprotein and lipoprotein profiles in serum samples were measured by 1 H-NMRS. We addressed the relationships between these biomarkers and CAN using correlation and regression analyses. Diagnostic performance was assessed by analyzing their areas under the receiver operating characteristic curves (AUC ROC )., Results: Three hundred and twenty-three patients were included (46% female, mean age and duration of diabetes of 41 ± 13 years and 19 ± 11 years, respectively). The overall prevalence of CAN was 28% [95% confidence interval (95%CI): 23; 33]. Glycoproteins such as N-acetylglucosamine/galactosamine and sialic acid showed strong correlations with inflammatory markers such as high-sensitive C-reactive protein, fibrinogen, IL-10, IL-6, and TNF-α. On the contrary, we did not find any association between the former and CAN. A stepwise binary logistic regression model (R 2  = 0.078; P = 0.003) retained intermediate-density lipoprotein-triglycerides (IDL-TG) [β:0.082 (95%CI: 0.005; 0.160); P = 0.039], high-density lipoprotein-triglycerides (HDL-TGL)/HDL-Cholesterol [β:3.633 (95%CI: 0.873; 6.394); P = 0.010], and large-HDL particle number [β: 3.710 (95%CI: 0.677; 6.744); P = 0.001] as statistically significant determinants of CAN. Adding these lipoprotein particles to a clinical prediction model of CAN that included age, duration of diabetes, and A 1c enhanced its diagnostic performance, improving AUC ROC from 0.546 (95%CI: 0.404; 0.688) to 0.728 (95%CI: 0.616; 0.840)., Conclusions: When added to clinical variables, 1 H-NMRS-lipoprotein particle profiles may be helpful to identify those patients with T1D at risk of CAN., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Aims/introduction: Deficiency of neurotropic factors is implicated in diabetic neuropathy (DN). Netrin-1 is a neurotropic factor, but its association with DN has not been explored. We have assessed the association between serum netrin-1 levels and early diabetic neuropathy assessed by quantifying corneal nerve fiber loss using corneal confocal microscopy., Materials and Methods: A total of 72 participants with type 2 diabetes, without and with corneal nerve fiber loss (DN- n = 42, DN+ n = 30), and 45 healthy controls were studied. Serum netrin-1 levels were measured by enzyme-linked immunosorbent assay, and corneal nerve morphology was assessed using corneal confocal microscopy., Results: Corneal nerve fiber density, branch density, fiber length and serum netrin-1 levels were significantly lower in the DN- and DN+ groups compared with controls (P < 0.001). Netrin-1 levels correlated with corneal nerve fiber length in the DN+ group (r = 0.51; P < 0.01). A receiver operating characteristic curve analysis showed that a netrin-1 cut-off value of 599.6 (pg/mL) had an area under the curve of 0.85, with a sensitivity of 76% and specificity of 74% (P < 0.001; 95% confidence interval 0.76-0.94) for differentiating patients with and without corneal nerve loss., Conclusions: Serum netrin-1 levels show a progressive decline with increasing severity of small nerve fiber damage in patients with diabetes. Netrin-1 could act as a biomarker for small nerve fiber damage in DN., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: The white blood cell count to mean platelet volume ratio (WMR) is considered a promising inflammatory marker, and its recognition is increasing. Inflammation is closely related to metabolic diseases such as diabetes and its complications. However, there are currently no reports on the correlation between WMR and type 2 diabetic peripheral neuropathy (DPN). This study aims to explore the correlation between WMR and DPN in type 2 diabetes patients. By understanding this association, we hope to provide a theoretical basis for preventing DPN through the improvement of inflammatory responses., Methods: This was a cross-sectional study involving 2515 patients with T2DM. Logistic regression analysis was conducted to assess the associations between WMR and DPN. Finally, the receiver operating characteristic curve (ROC curve) was employed to evaluate the predictive efficacy of WMR for DPN., Results: Patients in higher WMR quartiles exhibited increased presence of DPN. Additionally, WMR remained significantly associated with a higher odds ratio (OR) of DPN (OR 4.777, 95% confidence interval [CI] 1.296-17.610, P < 0.05) after multivariate adjustment. Moreover, receiver operating characteristic curve analysis indicated that the optimal cutoff value for WMR in predicting DPN presence was 0.5395 (sensitivity: 65.40%; specificity: 41.80%; and area under the curve [AUC]: 0.540)., Conclusions: In patients with T2DM, WMR was significantly increased in DPN and independently associated with an increased risk of DPN presence in Chinese patients. This suggests that WMR may serve as a useful and reliable biomarker of DPN, highlighting the importance of paying more attention to T2DM patients with high WMR to further prevent and reduce the development of DPN and related unfavorable health outcomes., (© 2024. The Author(s).)

About 20% of patients with diabetes suffer from chronic pain with neuropathic characteristics. We investigated the multivariate associations between 92 neurology-related proteins measured in serum from 190 patients with painful and painless diabetic neuropathy. Participants were recruited from the Pain in Neuropathy Study, an observational cross-sectional multicentre study in which participants underwent deep phenotyping. In the exploration cohort, two groups were defined by hierarchical cluster analyses of protein data. The proportion of painless vs painful neuropathy did not differ between the two groups, but one group had a significantly higher grade of neuropathy as measured by the Toronto Clinical Scoring System (TCSS). This finding was replicated in the replication cohort. Analyzing both groups together, we found that a group of 11 inter-correlated proteins (TNFRSF12A, SCARB2, N2DL-2, SKR3, EFNA4, LAYN, CLM-1, CD38, UNC5C, GFR-alpha-1, and JAM-B) were positively associated with TCSS values. Notably, EFNA4 and UNC5C are known to be part of axon guidance pathways. To conclude, although cluster analysis of 92 neurology-related proteins did not distinguish painful from painless diabetic neuropathy, we identified 11 proteins which positively correlated to neuropathy severity and warrant further investigation as potential biomarkers., (© 2024. The Author(s).)

Background: The evidence supporting a connection between elevated serum uric acid (SUA) levels and diabetic peripheral neuropathy (DPN) is controversial. The present study performed a comprehensive evaluation of this correlation by conducting a systematic review and meta-analysis of relevant research., Method: PubMed, Web of Science (WOS), Embase, and the Cochrane Library were searched for published literature from the establishment of each database to January 8, 2024. In total, 5 cohort studies and 15 cross-sectional studies were included, and 2 researchers independently screened and extracted relevant data. R 4.3.0 was used to evaluate the included literature. The present meta-analysis evaluated the relationship between SUA levels and the risk of DPN in type 2 diabetes (T2DM) by calculating the ratio of means (RoM) and 95% confidence intervals (CIs) using the method reported by JO Friedrich, and it also analyzed continuous outcome measures using standardized mean differences (SMDs) and 95% CIs to compare SUA levels between DPN and non-DPN groups. Funnel plot and Egger's test were used to assess publication bias. Sensitivity analysis was conducted by sequentially removing each study one-by-one., Results: The meta-analysis included 20 studies, with 12,952 T2DM patients with DPN and 16,246 T2DM patients without DPN. There was a significant correlation between SUA levels and the risk of developing DPN [odds ratio (OR) = 1.23; 95% CI: 1.07-1.41; p = 0.001]. Additionally, individuals with DPN had higher levels of SUA compared to those without DPN (SMD = 0.4; 95% CI: -0.11-0.91; p < 0.01)., Conclusion: T2DM patients with DPN have significantly elevated SUA levels, which correlate with a heightened risk of peripheral neuropathy. Hyperuricemia (HUA) may be a risk indicator for assessing the risk of developing DPN in T2DM patients., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024500373., Competing Interests: Author JG was employed by the company Amazon. The remaining 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 Zhang, Zhang, Li, Zhao, Wei, Shi, Yang, Fan, Zhao, Zhu, Du, Guo and Cao.)

Background and Objectives: Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM)., Methods: We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression., Results: We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users., Discussion: High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.

Pain is one of many complaints expressed by patients with diabetic polyneuropathy. However, no objective measure for pain severity has been available. Neurofilament light chains have been widely used for assessing axonal damage in the neuronal system. Hence, we sought to investigate whether neurofilament light chains can serve as a marker reflecting pain severity in diabetic polyneuropathy. We enrolled the patients with diabetic polyneuropathy. Serum concentrations of neurofilament light chain were then measured using a single-molecule array. Pain severity was evaluated using painDETECT and the Brief Pain Inventory. Moreover, laboratory results including, serum creatinine, HbA1c, and glomerular filtration rate. A correlation test was used to analyze each variable. A total of 42 patients were enrolled. Neurofilament light chain levels were unable to reflect current neuropathic pain severity. However, high levels of neurofilament light chain were a significant predictor of poor diabetes control (r = 0.41; p = 0.02) and kidney damage (r = 0.45; p = 0.01). Serum levels of neurofilament light chain could not reflect current pain severity but was strongly associated with kidney dysfunction and poor diabetes control. Other biomarkers that could predict pain severity need to be uncovered., (© 2024. The Author(s).)

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D ( n = 48, age 38 ± 4 years) and a healthy control group ( n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls ( p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = -0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria.

Aims: We have evaluated long-term weighted mean HbA 1c (wHbA 1c ), HbA 1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes., Materials and Methods: In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA 1c by integrating the area under all HbA 1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA 1c variability were computed as the standard deviation of all HbA 1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records., Results: In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA 1c, and increased HbA 1c variability. The lowest wHbA 1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy., Conclusions: More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA 1c of less than 62 mmol/mol (7.8%)., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Aims: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN)., Materials and Methods: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%. Prospective analyses used data from 505 participants without DSPN at baseline, of whom 125 had developed DSPN until the KORA FF4 survey. DSPN was defined based on the examination part of the Michigan Neuropathy Screening Instrument. Serum levels of neurological biomarkers were measured using proximity extension assay technology. Associations between 88 biomarkers and prevalent or incident DSPN were estimated using Poisson regression with robust error variance and are expressed as risk ratios (RR) and 95% CI per 1-SD increase. Results were adjusted for multiple confounders and multiple testing using the Benjamini-Hochberg procedure., Results: Higher serum levels of CTSC (cathepsin C; RR [95% CI] 1.23 (1.08; 1.39), p B-H  = 0.044) and PDGFRα (platelet-derived growth factor receptor A; RR [95% CI] 1.21 (1.08; 1.35), p B-H  = 0.044) were associated with prevalent DSPN in the total study sample. CDH3, JAM-B, LAYN, RGMA and SCARA5 were positively associated with DSPN in the diabetes subgroup, whereas GCP5 was positively associated with DSPN in people without diabetes (all p B-H for interaction <0.05). None of the biomarkers showed an association with incident DSPN (all p B-H >0.05)., Conclusions: This study identified multiple novel associations between neurological biomarkers and prevalent DSPN, which may be attributable to functions of these proteins in neuroinflammation, neural development and myelination., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM)., Methods: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated., Results: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients., Conclusion: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN)., Methods: The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60)., Results: The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995-1.000, P < 0.05). Serum Metrnl level was negatively correlated with age and SBP after a simple logistic regression analysis., Conclusion: Serum Metrnl concentration is independently correlated with DPN., (© 2024. The Author(s).)

Objective: To investigate the longitudinal development of neurofilament light chain (NfL) levels in type 2 diabetes with and without diabetic polyneuropathy (+/-DPN) and to explore the predictive potential of NfL as a biomarker for DPN., Research Design and Methods: We performed retrospective longitudinal case-control analysis of data from 178 participants of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Denmark (ADDITION-Denmark) cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-ups were analyzed for serum NfL (s-NfL) using single-molecule array, and the results were compared with established reference material to obtain NfL z-scores. DPN was diagnosed according to Toronto criteria for confirmed DPN at the 10-year follow-up., Results: s-NfL increased over time in +DPN (N = 39) and -DPN participants (N = 139) at levels above normal age-induced s-NfL increase. Longitudinal s-NfL change was greater in +DPN than in -DPN participants (17.4% [95% CI 4.3; 32.2] or 0.31 SD [95% CI 0.03; 0.60] higher s-NfL or NfL z-score increase in +DPN compared with -DPN). s-NfL at the 5-year follow-up was positively associated with nerve conduction studies at the 10-year follow-up (P = 0.02 to <0.001), but not with DPN risk. Areas under the curve (AUCs) for s-NfL were not inferior to AUCs for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated with higher DPN risk (odds ratio 1.36 [95% CI 1.08; 1.71] per 1 ng/L/year)., Conclusions: Our findings suggest that preceding s-NfL trajectories differ slightly between those with and without DPN and imply a possible biomarker value of s-NfL trajectories in DPN., (© 2024 by the American Diabetes Association.)

Background: Spexin is a novel peptide hormone and has shown antinociceptive effects in experimental mice. This study is aimed at evaluating the association of serum spexin level with diabetic peripheral neuropathy (DPN) and related pain in a Chinese population. Methods: We enrolled 167 type 2 diabetes mellitus (T2DM) including 56 patients without DPN (non-DPN), 67 painless DPN, and 44 painful DPN. Serum spexin was measured using ELISA. Logistic regression models were performed to analyze the independent effects of spexin on prevalence of DPN and painful DPN. In streptozotocin (STZ)-induced diabetic mice, mechanical pain threshold was measured using electronic von Frey aesthesiometer. Human peripheral blood mononuclear cells (PBMCs) were isolated and further stimulated with lipopolysaccharide without or with spexin. The gene expression was assayed by qPCR. Results: Compared with non-DPN, serum spexin level decreased in painless DPN and further decreased in painful DPN. The odds of DPN was associated with low spexin level in T2DM, which was similar by age, sex, BMI, and diabetes duration, but attenuated in smokers. The odds of having pain was associated with decreased spexin level in DPN, which was similar by age, sex, smoking status, and diabetes duration, but attenuated in normal weight. Furthermore, we observed that mechanical pain threshold increased in spexin-treated diabetic mice. We also found that lipopolysaccharide treatment increased the mRNA level of TNF- α , IL-6, and MCP-1 in human PBMCs, while spexin treatment prevented this increase. Conclusions: These results suggested that spexin might serve as a protective factor for diabetes against neuropathology and pain-related pathogenesis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ying Liu et al.)

Objective: To observe the clinical effect on diabetic peripheral neuropathy (DPN) treated with acupuncture combined with medication and explore its effect mechanism., Methods: Sixty-two patients of DPN were randomly divided into a combined therapy group (31 cases) and a medication group (31 cases, 2 cases dropped out); besides, 20 healthy subjects were recruited as a normal group. On the base of routine intervention, in the medication group, thioctic acid capsules were administrated orally, 0.2 g each time, 3 times a day. In the combined therapy group, besides the medication as the medication group, acupuncture was performed on bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Tianshu (ST 25), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) and the needles were retained for 30 min, acupuncture was delivered once daily, 6 times a week. The duration of treatment was 4 weeks in the two groups. The score of Toronto clinical scoring system (TCSS), the nerve conduction velocity of median nerve (MN) and common peroneal nerve (CPN) were observed before and after treatment in the two intervention groups; and the serum lipid metabolism was detected before and after treatment in the two intervention groups and the normal group., Results: Compared with that before treatment, the scores of TCSS were reduced in the combined therapy group and the medication group ( P <0.05) after treatment, and the score decrease in the combined therapy group was larger than that of the medication group ( P <0.001). The motor nerve conduction velocity and the sensory nerve conductive velocity of MN and CPN after treatment all increased in the combined therapy group and the medication group compared with those before treatment ( P <0.05), and the improvements in the combined therapy group were larger than those of the medication group ( P <0.001). Before treatment DPN patients had 365 differential lipid metabolites, including sphingosine (SPH, d18:0), involved in the inositol phosphate metabolism, compared with the subjects of the normal group. There were 103 differential lipid metabolites in the medication group before and after treatment, including lysophosphatidyl ethanolamine (LPE, 18:1/0:0), participated in glycerophospholipid metabolism. In the combined therapy group, before and after treatment, there were 99 differential lipid metabolites, including lysophosphatidylcholine (LPC, 18:0/0:0), participated in the neuroactive ligand-receptor interaction. Acupuncture greatly affected 50 lipid metabolites such as lysophosphatidic acid (LPA, 0:0/22:6), LPA(0:0/18:2) and LPC(O-18:0), which was mainly involved in glycerophospholipid metabolism., Conclusion: Acupuncture combined with medication ameliorates the symptoms and the nerve conduction velocity in DPN patients, which may be related to the regulation of serum lipid metabolism.

Introduction: Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B 12 (Vit B 12 )., Materials and Methods: This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN., Results: The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant., (© Journal of the Association of Physicians of India 2024.)

Glycemic variability (GV) has been related to complications in patients with diabetes. The aim of the systematic review and meta-analysis was to investigate whether GV is also associated with the incidence of diabetic peripheral neuropathy (DPN). A systematic search of Medline, Web of Science, Embase, and Cochrane Library database was conducted to identify relevant observational studies with longitudinal follow-up. The Newcastle-Ottawa Scale was used for study quality evaluation. A random-effects model was utilized to pool the results, accounting for heterogeneity. Ten observational studies including 72 565 patients with diabetes were included. The quality score was 8-9, indicating generally good quality of the included studies. With a mean follow-up duration of 7.1 years, 11 532 patients (15.9%) were diagnosed as DPN. Compared to patients with low GV, patients with high GV were associated with an increased risk incidence of DPN (risk ratio: 1.51, 95% confidence interval: 1.23 to 1.85, p<0.001; I2=78%). In addition, subgroup analysis showed consistent results in patients with type 1 and type 2 diabetes, and in studies evaluating the short-term and long-term GV (p for subgroup difference=0.82 and 0.53). Finally, results of subgroup analysis also suggested that the association between GV and risk of DPN were not significantly affected by study design, follow-up durations, diagnostic methods for DPN, adjustment of mean glycated hemoglobin A1c, or study quality scores (p for subgroup difference all>0.05). A high GV may be associated with an increased incidence of DPN., Competing Interests: The author declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN., Methods: In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011-2014 and followed up until 2019-2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow-up., Findings: After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR < 9.15) group was significantly higher than in the high baseline eGDR (eGDR ≥ 9.15) group (62.37% vs. 45.56%, p = .0013). The incidence of DPN was significantly higher in patients with sustained lower eGDR level (63.69%) compared with those with sustained higher eGDR level (35.80%). Subjects with low baseline eGDR (eGDR < 9.15) had significantly higher risk of DPN at the end of follow-up (odds ratio = 1.75), even after adjusting for other known DPN risk factors., Conclusions: The 5-year follow-up study highlights the importance of insulin resistance represented by eGDR in the development of DPN in T2DM. Diabetic patients with low eGDR are more prone to DPN and, therefore, require more intensive screening and more attention., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM)., Methods: A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019., Results: In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019., Conclusion: Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups., 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 Wang, Pai, Lin, Lee, Chen and Chang.)

Background: The systemic immuno-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are widely used and have been shown to be predictive indicators of various diseases. Diabetic nephropathy (DN), retinopathy (DR), and peripheral neuropathy (DPN) are the most prominent and common microvascular complications, which have seriously negative impacts on patients, families, and society. Exploring the associations with these three indicators and diabetic microvascular complications are the main purpose., Methods: There were 1058 individuals with type 2 diabetes mellitus (T2DM) in this retrospective cross-sectional study. SII, NLR, and PLR were calculated. The diseases were diagnosed by endocrinologists. Logistic regression and subgroup analysis were applied to evaluate the association between SII, NLP, and PLR and diabetic microvascular complications., Results: SII, NLR, and PLR were significantly associated with the risk of DN [odds ratios (ORs): 1.52, 1.71, and 1.60, respectively] and DR [ORs: 1.57, 1.79, and 1.55, respectively] by multivariate logistic regression. When NLR ≥2.66, the OR was significantly higher for the risk of DPN (OR: 1.985, 95% confidence interval: 1.29-3.05). Subgroup analysis showed no significant positive associations across different demographics and comorbidities, including sex, age, hypertension, HbA1c (glycated hemoglobin), and dyslipidemia., Conclusion: This study found a positive relationship between NLR and DN, DR, and DPN. In contrast, SII and PLR were found to be only associated with DN and DR. Therefore, for the diagnosis of diabetic microvascular complications, SII, NLR and PLR are highly valuable., 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 Li, Wang, Jia, Wang, Wang, Diao, Ou, Ma and Yang.)

Aims: We conducted a systematic review and meta-analysis to investigate the effect of exercise training on HbA1c, and on fasting and postprandial plasma glucose concentrations in patients with diabetic peripheral neuropathy (DPN)., Methods: Two independent researchers performed a systematic search in the electronic databases of PubMed, Web of Science and Scopus. Studies investigating the effect of exercise training on patients diagnosed with DPN using a randomized-controlled design were included in the meta-analysis., Results: Of 1254 retrieved studies, 68 studies were identified to undergo full-text review; out of these a total of 13 randomized trials met the inclusion criteria. Eleven studies assessed HbA1c, 8 fasting plasma-glucose concentration, and 3 postprandial plasma-glucose concentration. Overall, exercise training significantly decreased HbA1c [-0.54% (95% CI -0.78 to -0.31%)], fasting plasma glucose [-32.6 mg/dl [-1.8 mmol/L] (-44.2 to -20.9 mg/dl [-2.4 to -1.1 mmol/L])] and postprandial plasma glucose [-67.5 mg/dl [-3.7 mmol/L] (-129.5 to -5.4 mg/dl [-7.1 to -0.3 mmol/L])]. Studies with aerobic training intervention yielded the largest significant mean reduction in HbA1c (-0.75%) and fasting plasma glucose concertation (34.0 mg/dl)., Conclusions: aerobic training is the most effective modality to reduces HbA1c, fasting and postprandial plasma glucose concentration in patients with DPN. From a metabolic perspective, the magnitude precision range of the reduction in HbA1c is of clinical importance for patients with DPN. This area of research warrants further attention to investigate the impact of various exercise modalities on glycemic control. Registration number CRD42023413687., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes mellitus (T2DM). A comprehensive understanding of DPN's causal factors is pivotal for effective prevention and treatment, but the precise clinical pathogenesis remains unclear., Objective: To investigate the correlation between blood selenium (Se) levels and DPN in T2DM patients and analyze factors contributing to lesion development., Methods: We selected 51 patients with DPN and 57 with T2DM alone between June 2021 and August 2022. Blood glucose, lipid, and Se levels were assessed. Electromyographic evoked potentials measured motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) in DPN patients., Results: DPN patients exhibited lower Se, MNCV, and SNCV compared to DM patients, with higher glucose and lipid levels (P < .05). Logistic regression analysis identified age (95%CI 1.256-9.631), disease duration (95%CI 2.160-11.816), fasting blood glucose (95%CI 2.160-11.816), and HbA1c (95%CI 1.064-7.632) as independent risk factors for DPN in T2DM, while Se (95%CI 0.324-1.126) emerged as an independent protective factor (P < .05)., Conclusions: Blood selenium levels and DPN are closely related, with selenium emerging as a significant factor in DPN occurrence among T2DM patients.

Aims: To investigate whether higher serum CCL11/Eotaxin-1, a biomarker for aging and neurodegenerative and neuroinflammatory disorders, is associated with diabetic sensorimotor polyneuropathy (DSPN), peripheral nerve dysfunction, and cardiac autonomic neuropathy in people with type 2 diabetes., Methods: This cross-sectional study included 106 patients with type 2 diabetes and 40 healthy controls, matched for the age and sex distribution of the diabetes group as a whole. The CC chemokines CCL11/Eotaxin-1 and CCL22/MDC were measured in fasting serum samples. DSPN and peripheral nerve function were assessed by neurological examination and nerve conduction studies, and cardiac autonomic function, by heart rate variability (HRV) and corrected QT (QTc) time. The cardio-ankle vascular index (CAVI) was measured as a marker for arterial stiffness., Results: Serum CCL11/Eotaxin-1 levels were significantly higher in diabetic patients than in healthy controls (183 ± 63.5 vs. 113.1 ± 38.5 pg/ml, p  < 0.001), but serum CCL22/MDC levels were not significantly different between the two groups. In the diabetes group, the serum CCL11/Eotaxin-1 level was positively correlated with ulnar and sural nerve conduction velocities ( p  = 0.0009, p  = 0.0208, respectively) and sensory nerve action potential ( p  = 0.0083), and CAVI ( p  = 0.0005), but not with HRV indices or QTc time, and serum CCL22/MDC was not significantly correlated with any indices of nerve conduction. In a model adjusted for age and duration of diabetes, serum CCL11/Eotaxin-1 was still associated with ulnar nerve conduction velocity ( p  = 0.02124). Serum CCL11/Eotaxin-1, but not CCL22/MDC, was significantly higher in patients with than in those without DSPN (208.2 ± 71.6 vs. 159.1 ± 45.1 pg/ml, respectively; p  < 0.0001)., Conclusions: Serum CCL11/Eotaxin-1 is elevated in patients with DSPN and is associated with peripheral nerve dysfunction, in particular sensory nerve conduction velocity, suggesting that serum CCL11/Eotaxin-1 may be a potential biomarker for DSPN., Clinical Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000040631).

Background: Many studies have examined the role of inflammation in the development of diabetic neuropathy (DPN)., Objective: Evaluate the relation of the serum level of Transforming Growth Factor-β and Tumor Necrosis Factor-α and development of diabetic peripheral neuropathy DPN., Methods: In a case-control study, randomly selected 140 diabetic patients were included, the randomly selected patients were divided equally and matched into a case group who have diabetic peripheral neuropathy and diabetic neuropathy-free patients as a control group. For both groups whole blood sample was examined to compare for (TGF-β), and (TNF-α) levels determination by ELISA technique., Results: The age of the study samples ranged from 25 to 80 years with a male ratio of 1.45:1 although the sex differences between both groups were not significant. The mean levels of (TNF-α) and (TGF-β) was significantly higher among cases group than that of controls group (254.86 ± 75.9 vs158.01 ± 50.600) for TNF-α and for TGF- β (312.85 ± 62.27 vs. 217.82 ± 52.95) respectively. Both TNF-α and TGF-β have high sensitivity and specificity in detection of DPN. The sensitivity of TNF-α was 95.7% and specificity of 61.4% area under the ROC curve (AUC) of 0.870 ± 0.029, while the sensitivity of TGF-β was 91.4%, and specificity of 67.1 with good area under the ROC curve (AUC) of 0.891 ± 0.026 (P=0.000)., Conclusions: TNF-α and TGF -β are significantly elevated levels in patients with DPN, these cytokines could be used as indicators for the development of DPN.

Background: Diabetic Peripheral Neuropathy (DPN) is a chronic complication in Type 2 Diabetes Mellitus (T2DM) patients and is characterized by paresthesia, pain, and hypoesthesia of the extremities. The Diabetic Neuropathy Symptom-Score (DNS) is a quick, inexpensive, and easy-to-perform tool to detect DPN in clinical practice. Biochemical markers like Nitric Oxide (NO) and Vascular Endothelial Growth Factor (VEGF) play a role in the early detection of DPN. This study aims to investigate the relationship between risk factors and these biomarkers. So, it is expected to improve the prevention and treatment of diabetic neuropathy more effectively., Method: A cross-sectional method was used for this study. The sample size was 85 patients with T2DM who visited several primary healthcare in Medan, selected by consecutive sampling method based on eligibility criteria. Data collected included DNS, assessment of NO, VEGF, Glycated Hemoglobin (HbA1c), plasma blood glucose (PBG), and lipid profile. The collected data were analyzed using an independent T-test., Result: The results showed that most T2DM patients, namely 73 people (85.9%), experienced DPN. From the bivariate analysis results, the risk factors associated with the prevalence of DPN in T2DM patients were found to be increased levels of total cholesterol, HbA1c, NO, and VEGF (p < 0.05). Meanwhile, blood pressure, fasting BGL, HDL-C, LDL-C, and triglycerides were not related to the occurrence of DPN in this study (p> 0.05)., Conclusion: DNS can be used as a quick and easy initial screening tool implemented in clinical practice for screening DPN. Diabetic patients with DPN tend to have lower NO and increased VEGF; besides, NO levels are also associated with the progression of DPN. Furthermore, education, blood sugar control, and physical exercise, especially leg exercises, can prevent progressive DPN., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P&lt;0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P&lt;0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P&lt;0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P&lt;0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P&lt;0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Two dimensional GC (GC × GC)-time-of-flight mass spectrometry (TOFMS) has been used to improve accurate metabolite identification in the chemical industry, but this method has not been applied as readily in biomedical research. Here, we evaluated and validated the performance of high resolution GC × GC-TOFMS against that of GC-TOFMS for metabolomics analysis of two different plasma matrices, from healthy controls (CON) and diabetes mellitus (DM) patients with kidney failure (DM with KF). We found GC × GC-TOFMS outperformed traditional GC-TOFMS in terms of separation performance and metabolite coverage. Several metabolites from both the CON and DM with KF matrices, such as carbohydrates and carbohydrate-conjugate metabolites, were exclusively detected using GC × GC-TOFMS. Additionally, we applied this method to characterize significant metabolites in the DM with KF group, with focused analysis of four metabolite groups: sugars, sugar alcohols, amino acids, and free fatty acids. Our plasma metabolomics results revealed 35 significant metabolites (12 unique and 23 concentration-dependent metabolites) in the DM with KF group, as compared with those in the CON and DM groups (N = 20 for each group). Interestingly, we determined 17 of the 35 (14/17 verified with reference standards) significant metabolites identified from both the analyses were metabolites from the sugar and sugar alcohol groups, with significantly higher concentrations in the DM with KF group than in the CON and DM groups. Enrichment analysis of these 14 metabolites also revealed that alterations in galactose metabolism and the polyol pathway are related to DM with KF. Overall, our application of GC × GC-TOFMS identified key metabolites in complex plasma matrices., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To analyze the associations of circulating C1q/tumor necrosis factor-related protein-3 (CTRP3) concentrations with several metabolic parameters and to investigate the possible role of CTRP3 in subjects with diabetic peripheral neuropathy (DPN)., Research Design and Methods: A total of 347 participants were recruited in this study, and plasma CTRP3 concentrations were analyzed in subjects with DPN (n=172) and without DPN (non-DPN, n=175). The nerve conduction test and oral glucose tolerance test were performed, and Neuropathy Symptom Score (NSS)/Neuropathy Disability Score (NDS) and biochemical parameters were measured in all participants., Results: Plasma CTRP3 concentrations were significantly lower in patients with DPN compared with those in patients with diabetes without DPN (p<0.01), despite the comparable glucose and lipid metabolism levels in both groups. Groups with a higher plasma CTRP3 level had a faster nerve conduction velocity. In addition, plasma CTRP3 concentrations were negatively correlated with hemoglobin A1c (HbA1c), urea acid (UA), triglyceride, NSS and NDS (p<0.05) after being adjusted for age and sex. Multivariate logistic regression analysis revealed that plasma CTRP3 concentrations were significantly correlated with DPN after being controlled for age, sex, body mass index, HbA1c, blood pressure, lipid profiles, and renal function., Conclusions: Plasma CTRP3 concentrations were significantly lower in patients with DPM and positively correlated with nerve conduction velocity. The relationship between CTRP3 levels and DPN is independent of the glucose and lipid status. Therefore, circulating CTRP3 might serve as a predictor of impairment of nerve conduction in patients with DPN., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the significance and clinical value of dynamic monitoring of lipid metabolism indexes in patients with diabetic peridiabetic lesions., Methods: A total of 192 patients with type 2 diabetes (T2DM) treated in our hospital from October 2019 to July 2021 were divided into two groups according to whether they were complicated with peripheral neuropathy (DPN). The patients in the observation group were randomly assigned into group A ( n = 45) and group B ( n = 45) according to the method of random number table. The patients were assigned into control group ( n = 102) and observation group ( n = 90), and the patients in the observation group were randomly divided into two groups ( n = 45). All the patients in the three groups were given routine hypoglycemic treatment, and group B was observed to dynamically monitor the indexes of lipid metabolism and regulate blood lipids on the basis of routine hypoglycemic treatment. The indexes of lipid metabolism, including total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C), were detected before treatment. The receiver operating curve (ROC) was applied to elucidate the efficacy of TC, TG, and HDL-C and LDL-C in predicting peripheral neuropathy (DPN) in patients with T2DM. The indexes of lipid metabolism and neurological function of patients were determined after the treatment. The difference was considered to be statistically significant ( P < 0.05)., Results: In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, with HDL-C significantly lower. ROC curve analysis indicated that the area under the curve (AUC) of serum TG level to predict peripheral neuropathy in patients with T2DM was 0.753 (95% CI = 0.604 - 0.901, P = 0.007). When the Youden index reached the maximum (0.677), with corresponding sensitivity and specificity 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L, the AUC of serum TC level for predicting peripheral neuropathy in patients with T2DM was 0.851 (95% CI = 0.735 ~ 0.967 P < 0.001); when the Youden index reaches its maximum (0.750), with the sensitivity and specificity 84.44% and 92.06%, respectively, and the critical value is 4.52 mmol/L, the AUC of predicting peripheral neuropathy in patients with T2DM by serum LDL-C level was 0.799 (95% CI = 0.52 ~ 0.946, P = 0.001); when the Youden index reaches its maximum (0.706), with sensitivity and specificity 80.58% and 87.24%, respectively, and the critical value is 3.36 mmol/L, the AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI = 0.568 ~ 0.886 P = 0.014). When the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L. The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI = 0.839 ~ 0.978 P < 0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased ( P < 0.05). The motor nerve conduction velocity and sensory nerve conduction velocity of median nerve and peroneal nerve in group B were higher than those in group A ( P < 0.05)., Conclusion: Diabetic patients with severe lipid metabolic disorders have a higher risk of DPN. Combined detection of lipid metabolism indexes such as TC, TG, and HDL-C and LDL-C is effective in predicting diabetic patients with DPN. In clinic, through dynamic monitoring of lipid metabolism indexes, we can actively regulate the level of blood lipids in patients with T2DM, which can delay the occurrence and development of DPN to a certain extent, as well as improving the prognosis of patients with diabetes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wei Wang et al.)

Background: Diabetic peripheral neuropathy (DPN) is one of the most common chronic microvascular complications in type 2 diabetes mellitus (T2DM). Hence, the present study aimed to investigate the association between Serum Uric Acid (SUA) levels and diabetic peripheral polyneuropathy in patients with type 2 diabetes., Methods: We performed this case-control study during 2019-2020 on individuals with diabetes referring to the Razi clinic of Rasht, in the north of Iran. Polyneuropathy in patients was assessed based on the Neuropathy Disability Score (NDS), Diabetic neuropathy symptom score (DNS) scoring system, and electromyography (EMG)/nerve conduction velocity (NCV). The inclusion criterion for the control group was normal EMG/NCV. Then, the patients were assessed for SUA level and also laboratory results., Results: In total, 230 patients with type 2 diabetes were examined. The mean SUA level in the DPN group was significantly higher compared to the control group (6.72 ± 1.75 vs. 4.57 ± 1.49 mg/dL). With increasing the SUA, the odds of developing neuropathy increased by 2.2 times (OR = 2.2). The risk factors for diabetic polyneuropathy included gender (male) (OR = 0.347), SBP (OR = 1.1), retinopathy (OR = 3.29), and microalbuminuria (OR = 4.44). The chance of developing polyneuropathy in patients with retinopathy was 3.3 times higher than in the control group, it was 4.4 times in microalbuminuria patients., Conclusion: Elevated SUA level increased the chance of developing peripheral polyneuropathy in a person with type 2 diabetes. SUA levels higher than 5.25 mg / dL expose a person with type 2 diabetes to developing peripheral polyneuropathy., (© 2022. The Author(s).)

Aims: The objective of this study is to explore the relationship between serum 25-hydroxyvitamin-D(25-(OH) 2 D 3 ) level and sweat function in patients with type 2 diabetes mellitus (T2DM)., Methods: A cross-sectional study of 1021 patients with T2DM who underwent 25-(OH) 2 D 3 level detections and sweat function tests was carried out. These individuals were divided into deficient groups (n = 154 cases), insufficient groups (n = 593 cases) and sufficient groups (n = 274 cases). Spearman correlation analysis and multivariate stepwise linear regression analysis were implemented to determine the association of 25-(OH)2D3 level and sweat function., Results: The total presence of sweating dysfunction was 38.59%. Patients with a lower level of serum 25-(OH) 2 D 3 had more severe sweat secretion impairment (P < 0.05). As the decrease of serum 25-(OH) 2 D 3 level, the presence of sweating dysfunction increased (P < 0.05). 25-(OH) 2 D 3 level was positively correlated with sweat function parameters, age and duration of T2DM were negatively correlated with sweat function parameter (P < 0.05). Multivariate stepwise linear regression analysis explored a significant association between serum 25-(OH) 2 D 3 level with sweat function (P < 0.05)., Conclusions: Serum 25-(OH) 2 D 3 level was positively correlated with sweat function in patients with T2DM., (© 2021. Italian Society of Endocrinology (SIE).)

Neuroinflammation contributes significantly to the pathogenesis of diabetic peripheral neuropathy (DPN). Quercetin reportedly exerts neuroprotective effects in DPN. Here, we aimed to evaluate the potential anti-inflammatory effects of quercetin in a DPN rat model. Eight weeks after streptozotocin administration, diabetic rats were treated with quercetin (30 and 60 mg/kg/day orally) for 6 weeks. We assessed the mechanical withdrawal threshold (MWT), nerve conduction velocity (NCV) and morphological changes in sciatic nerves. Additionally, we measured the levels of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 by ELISA and the expression of TLR4, MyD88, and NF-κB in sciatic nerves by western blotting and immunohistochemical assays. Our results revealed that blood glucose levels and body weight were unaltered following quercetin treatment. However, quercetin improved MWT (p < 0.05), NCV (p < 0.05), and pathological changes in the sciatic nerves of DPN rats. Quercetin significantly alleviated the increased expression of TNF-α (p < 0.05) and IL-1β (p < 0.001). Furthermore, high-dose quercetin administration significantly downregulated the expression of TLR4 (p < 0.001), MyD88 (p < 0.001), and NF-κB (p < 0.001) in sciatic nerves of DPN rats. Our findings revealed that quercetin could reduce the levels of inflammatory factors in DPN rats, possibly mediated via the downregulation of the TLR4/MyD88/NF-κB signalling pathway. Collectively, these results suggest that although quercetin did not decreased blood glucose levels or reversed the reduced body weight, it showed anti-inflammatory and neuroprotective effects, which was beneficial for the treatment of DPN., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Previous studies exploring the influence of glycemic variability (GV) on the pathogenesis of distal symmetrical polyneuropathy (DSPN) in type 1 diabetes (T1DM) produced conflicting results. The aim of this study was to assess the relationship between GV and DSPN in T1DM. Adults with T1DM were included in this cross-sectional study and asked to undergo 3-day CGM. GV quantified by coefficient of variation (CV) and mean amplitude of glucose excursions (MAGE) were obtained from CGM. Clinical characteristics and biochemical assessments were collected for analysis. The study comprised 152 T1DM patients (53.9% males) with mean age of 44.2 year. Higher levels of age and duration of diabetes and lower levels of total cholesterol, LDL, fasting C-peptide and postprandial C-peptide were observed in DSPN subjects. DSPN groups displayed a higher blood glucose between 00:00 and 12:59 according to the CGM profile. Higher MAGE and CV were associated with increased risk of DSPN in the fully adjusted model. Meanwhile, a significant association between measurements of hypoglycemia, especially nocturnal hypoglycemia, and DSPN was found after multiple tests. CGM parameters describing the glycemic variability and hypoglycemia were potential risk factors for DSPN in adults with T1DM., (© 2021. The Author(s).)

Background and Aims: Musculoskeletal manifestations (carpal tunnel syndrome, Dupuytren's contracture, etc.) may occur in poorly controlled and longstanding diabetes. In this study, we evaluated the relationship of musculoskeletal diseases with microvascular and macrovascular complicationsin patients with diabetes., Methods: A total of 600 patients with diabetes were enrolled in this cross-sectional study. Demographic data and historical records of the patients were retrieved. Musculoskeletal diseases were assessed by clinical examinations and then confirmed by a rheumatologist., Results: Out of the 600 patients with diabetes, 61.5% (369/600) were female and 38.5% (231/600) were male. Diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy, CVA, and diabetes related ischemic heart disease were rated as 43.1%, 33.2%, 7.8%, 7.5%, and 39.6%, respectively. Significant gender differences were observed in the rates of diabetic nephropathy [56.28% for women and 43.71% for men (p value < 0.000)], diabetic peripheral neuropathy [72.34% for women and 27.65% for men (p value < 0.002)], and ischemic heart disease [57.98% for women and 42.01% for men(p value < 0.001)]., Conclusion: Musculoskeletal diseases usually occur in patients with poorly controlled and long-term diabetes. Due to the clear association of microvascular complications with musculoskeletal disease, more attention should be paid to the early detection of these complications in patients with diabetes., Competing Interests: Declaration of competing interest No conflicts of interest exist for Mahdie Fatollahzade and other authors as well as there is no secondary interest, such as financial again., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Aims/introduction: This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy., Materials and Methods: This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy., Results: A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05)., Conclusions: Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)