Diabetic Neuropathy Research Articles

Association of peripheral neuropathy with dry eye disease and meibomian gland dysfunction in patients with type 1 diabetes.

To explore the relationship between dry eye disease and type 1 diabetes mellitus (DM) and also to identify whether diabetic peripheral neuropathy (DPN) was a significant predictor for the development of dry eye disease. This prospective cross sectional study involved patients with type 1 DM and aged- and sex-matched healthy controls. All of the participants underwent dry eye tests including meibomian gland function. Based on neurologic examination and electromyography findings, diabetic patients were grouped as DPN + and DPN-. All findings were compared and predictive factors for dry eye disease were identified. Of the 97 patients with type 1 DM, 42 (43.3%) were diagnosed as DPN. In patients with DM, there was a significant increase in the ocular surface disease index, corneal surface staining, eyelid margin abnormality and meibomian gland dysfunction and a significant decrease in tear break-up time and Schirmer's I test (p < 0.05). Measurements of dry eye tests were more severe with the presence of DPN (p < 0.05). Age of the patients, duration of DM and HbA1c level were significantly correlated with ocular surface and meibomian gland dysfunction parameters (p < 0.05). Age of the patients (p < 0.001), duration of DM (p = 0.001), HbA1c level (p = 0.036) and presence of DPN (p < 0.001) were found to be the independent and significant predictors of dry eye disease. Type 1 DM was found to be significantly associated with ocular surface abnormalities including meibomian gland dysfunction. Furthermore, age of the patients, duration of DM, HbA1c level and presence of DPN were predictive factors of dry eye disease in type 1 DM.

Fast Analgesic Effect in Response Test with Topical Phenytoin Cream Correlates with Prolonged Pain Relief After Extended Use in Painful Diabetic Neuropathy

Fast Analgesic Effect in Response Test with Topical Phenytoin Cream Correlates with Prolonged Pain Relief After Extended Use in Painful Diabetic Neuropathy

Nerve Conduction Study, Sympathetic Skin Response Test, and Demographic Correlates in Type 2 Diabetes Mellitus Patients.

To comprehensively assess the relationship between nerve conduction study (NCS), sympathetic skin response (SSR), and demographic factors in patients with diabetic neuropathy, exploring potential risk factors and mechanisms. A retrospective study (N=184) included patients diagnosed with type 2 diabetes mellitus undergoing NCS and SSR. Demographic, clinical, and laboratory data were analyzed. Patients were categorized by diabetic peripheral neuropathy (DPN) and SSR stages for comparative analysis. HbA1c levels correlated with DPN progression. SSR stages exhibited age-related differences. Height correlated with DPN but not SSR stages. Body mass index showed no significant differences. While DPN progression correlated with glycemic control and duration of diabetes, SSR was influenced by age. Unexpectedly, cholesterol levels remained within the normal range, challenging established concepts. Understanding these relationships is crucial for interpreting test results and developing targeted interventions for diabetic neuropathy.

Alpha-Tocopherol-Loaded Liposomes Reduce High Glucose Induced Oxidative Stress in Schwann Cells: A Proof of Concept Study.

Although oxidative stress is the main pathophysiology of the development of diabetic neuropathy, oral administration of antioxidants has given disappointing results. Here, we hypothesized that local delivery of antioxidants would provide protective effects on Schwann cells due to the high concentration of local lesions. We prepared alpha-tocopherol (ATF)-loaded liposomes and tested their skin penetration after sonication. An in vitro study using IMS-32 cells was conducted to determine the level of reactive oxygen species (ROS) scavenging effects of ATF-liposomes. ATF reduced ROS in high-glucose-exposed IMS-32 cells in a dosedependent manner. ATF-liposomes also reduced the ROS level in vitro and ultrasound irradiation enhanced delivery to the dermis in porcine ear skin. This study showed that it is feasible to deliver ATF through the skin and can effectively reduce ROS. This model is worthy of development for clinical use.

Association between atherogenic index of plasma and type 2 diabetic complications: a cross-sectional study

BackgroundThe Atherogenic Index of Plasma (AIP) was originally developed primarily as a marker for assessing atherosclerosis. Consequently, this study investigates the potential association between AIP and type 2 diabetic complications through a cross-sectional design.MethodsThe National Metabolic Management Center(MMC) serves as a comprehensive platform dedicated to the establishment of standardized protocols for the diagnosis, treatment, and long-term follow-up of metabolic diseases. Following the relevant inclusion and exclusion criteria, a total of 3,094 patients were enrolled for subsequent analysis. In this study, logistic regression, restricted cubic splines, and subgroup analyses were employed to evaluate the association between the AIP and four major complications of type 2 diabetes, namely, type 2 diabetes with carotid atherosclerosis (DA), diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN).ResultsThe logistic regression results demonstrate that in the fully adjusted model, each SD increase in AIP correlates with an elevated risk of type 2 diabetic kidney disease (DKD), with the risk of kidney damage intensifying alongside higher AIP groupings. The RCS analysis and subgroup analyses similarly revealed a dose-response relationship between AIP levels and the risk of DKD. Furthermore, the AIP was not found to be statistically significantly associated with DA, DR,and DPN.ConclusionsThe AIP may serve as a valuable predictive indicator for evaluating kidney damage in patients with type 2 diabetes, and regular screening of AIP in this population could provide significant benefits in the prevention of DKD.

Vision transformers for automated detection of diabetic peripheral neuropathy in corneal confocal microscopy images

Early detection and management of diabetic peripheral neuropathy (DPN) are critical to reducing associated morbidity and mortality. Corneal Confocal Microscopy (CCM) facilitates the imaging of corneal nerves to detect early and progressive nerve damage in DPN. However, its wider adoption has been limited by the subjectivity and time-intensive nature of manual nerve fiber quantification. This study investigates the diagnostic utility of state-of-the-art Vision Transformer (ViT) models for the binary classification of CCM images to distinguish between healthy controls and individuals with DPN. The ViT model's performance was also compared to ResNet50, a convolutional neural network (CNN) previously applied for DPN detection using CCM images. Using a dataset of approximately 700 CCM images, the ViT model achieved an AUC of 0.99, a sensitivity of 98%, a specificity of 92%, and an F1-score of 95%, outperforming previously reported methods. These findings highlight the potential of the ViT model as a reliable tool for CCM-based DPN diagnosis, eliminating the need for time-consuming manual image segmentation. Moreover, the results reinforce CCM's value as a non-invasive and precise imaging modality for detecting nerve damage, particularly in neuropathy-related conditions such as DPN.

Gastrointestinal autonomic neuropathy in patients with type 2 diabetes mellitus: features of diagnosis and treatment

Diabetes mellitus (DM) type 2 is one of the components of metabolic syndrome. One of the most common complications of type 2 diabetes is diabetic neuropathy, which results in damage to peripheral and/or autonomic nerve fibers. Disorders of the autonomic nervous system - diabetic autonomic neuropathy (DAN)-can occur in up to 60% of patients. One form of GAN is gastrointestinal autonomic neuropathy (GAN). There is no exact information about its prevalence due to the complexity of diagnosis, but according to some data, symptoms occur in half of patients with diabetes. The main manifestations of GAN are esophageal motility disorders (heartburn, reflux), gastroparesis (nausea, vomiting, feeling of fullness), intestinal motility disorders (diarrhea, constipation), anorectal dysfunction (fecal incontinence). Impaired gastrointestinal motility, in particular gastroparesis, leads to changes in the pharmacokinetics of oral glucose-lowering drugs, which reduces their effectiveness. And in patients receiving insulin therapy, impaired movement of food through the gastrointestinal tract can lead to hypoglycemia. In this regard, identifying and treating manifestations of GAN is an important aspect of managing a patient with type 2 diabetes. Diagnosis of GAN should be aimed at excluding other causes of gastrointestinal disorders and includes, depending on the clinical manifestations, fibrogastroduodenoscopy, barium radiography, colonoscopy, etc. The “gold standard” for diagnosing gastroparesis is considered to be measuring gastric emptying using scintigraphy of digested solids, but due to the high cost and complexity of the procedure, this method is not used in routine practice. The main therapeutic measures in the management of patients with diabetes and GAN are glycemic compensation, compliance with nutritional recommendations, treatment of neuropathy and symptomatic therapy.

Physiological mechanisms of neuromuscular impairment in diabetes-related complications: Can physical exercise help prevent it?

Diabetes mellitus is a chronic disorder that progressively induces complications, compromising daily independence. Among these, diabetic neuropathy is particularly prevalent and contributes to substantial neuromuscular impairments in both types 1 and 2 diabetes. This condition leads to structural damage affecting both the central and peripheral nervous systems, resulting in a significant decline in sensorimotor functions. Alongside neuropathy, diabetic myopathy also contributes to muscle impairment and reduced motor performance, intensifying the neuromuscular decline. Diabetic neuropathy typically implicates neurogenic muscle atrophy, motoneuron loss and clustering of muscle fibres as a result of aberrant denervation-reinervation processes. These complications are associated with compromised neuromuscular junctions, where alterations occur in pre-synaptic vesicles, mitochondrial content and post-synaptic signalling. Neural damage is intensified by chronic hyperglycaemia and oxidative stress, exacerbating vascular dysfunction and reducing oxygen delivery. These complications imply a severe decline in neuromuscular performance, evidenced by reductions in maximal force and power output, rate of force development and muscle endurance. Furthermore, diabetes-related complications are compounded by age-related degenerative changes in long-term patients. Aerobic and resistance training offer promising approaches for managing blood glucose levels and neuromuscular function. Aerobic exercise promotes mitochondrial biogenesis and angiogenesis, supporting metabolic and cardiovascular health. Resistance training primarily enhances neural plasticity, muscle strength and hypertrophy, which are crucial factors for mitigating sarcopenia and preserving functional independence. This topical review examines current evidence on the physiological mechanisms underlying diabetic neuropathy and the potential impact of physical activity in counteracting this decline.

Quantifying Cognitive Function in Diabetes: Relationships Between AD8 Scores, HbA1c Levels, and Other Diabetic Comorbidities

Background/Objectives: Dementia associated with diabetes mellitus (DM) has been well documented in the literature, but studies utilizing early screening tools to target populations with mild cognitive dysfunction remain limited. This study aimed to investigate early cognitive decline by studying the relationships between “Ascertain Dementia 8” (AD8) questionnaire scores and glycemic control, lipid profiles, estimated glomerular filtration rate (eGFR), and the complications of diabetes. Methods: This case–control, cross-sectional, observational study was conducted at a medical center and an affiliated regional hospital in southern Taiwan from 30 June 2021 to 30 June 2023. Patients diagnosed with type 2 diabetes mellitus aged ≥40 years were recruited. Their past medical history, biochemical data, and AD8 score were collected at the same time. Results: The patients with glycated hemoglobin (HbA1c) levels of ≥7% had a higher risk of cognitive impairment than those with HbA1c levels of &lt;7% (p &lt; 0.001). The participants whose eGFR was &lt;60 mL/min/1.73 m2 had a higher mean AD8 score compared to those with an eGFR of ≥60 mL/min/1.73 m2 (p = 0.008). The patients with a medical history of peripheral artery disease and diabetic neuropathy were also associated with a higher mean AD8 score (p &lt; 0.001 and p = 0.017, respectively). Conclusions: By employing the AD8 questionnaire as a sensitive screening tool, our study suggests that early cognitive decline is significantly associated with poorer glycemic control, a lower glomerular filtration rate, peripheral artery disease, and diabetic neuropathy. Early detection of these risk factors may facilitate timely interventions and tailored treatment strategies to treat or prevent cognitive dysfunction.

Probiotics alleviate painful diabetic neuropathy by modulating the microbiota–gut–nerve axis in rats

Painful diabetic neuropathy (PDN) is one of the most common complications of diabetes. Recent studies suggested that gut microbiota dysbiosis contributes to the development of PDN, but underlying mechanisms remain elusive. In this study, we found decreased probiotics generating bacteria such as Lactobacillus and Bifidobacterium strains in the PDN rats. Supplementation with multiple probiotics for 12 weeks alleviated pain, reversed nerve fiber lesions, and restored neuronal hyperexcitability. Probiotics administration effectively attenuated intestinal barrier impairment, reduced serum lipopolysaccharide and proinflammatory cytokines, and mitigated disruptions in the blood-nerve barrier. Furthermore, probiotics treatment inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway and reduced proinflammatory cytokines in the sciatic nerve of the PDN rats. Together, our findings suggest that gut microbiota dysbiosis participates in PDN pathogenesis, and probiotics offer therapeutic potential via modulating the microbiota-gut-nerve axis.Graphical abstract

Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme implicated in inflammation and oxidative stress, and has been associated with cardiovascular conditions and adverse outcomes, particularly in diabetes and its complications. However, no prior studies have examined the relationship between Lp-PLA2 and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This research aims to explore the potential association between Lp-PLA2 and DPN. This retrospective study included 880 hospitalized patients with T2DM treated between March 2024 and August 2024 at Nanjing First Hospital. To assess the relationship between Lp-PLA2 and DPN, multiple logistic regression models were applied. The study also utilized restricted cubic spline (RCS) modeling, segmented regression, stratified analysis, and receiver operating characteristic (ROC) curve assessments. Patients diagnosed with DPN exhibited elevated Lp-PLA2 levels compared to those without DPN. Even after adjusting for multiple variables, Lp-PLA2 was independently associated with a higher likelihood of DPN (odds ratio [OR] 1.011, 95% confidence interval [CI] 1.008-1.014, P<0.001). The RCS analysis revealed a nonlinear association, with an inflection point at 215.8ng/mL. In ROC curve analysis, the area under the curve (AUC) for Lp-PLA2 was 0.664, while the combined indicator AUC was 0.739. Serum Lp-PLA2 levels show a significant correlation with the presence of DPN in patients with T2DM. These findings suggest that Lp-PLA2 could serve as a valuable biomarker for identifying patients at risk for DPN, emphasizing the need for close monitoring of T2DM individuals with elevated Lp-PLA2 to mitigate the risk of developing DPN and associated adverse health outcomes.

Early Detection of Diabetic Peripheral Neuropathy in Diabetic Patients: A Cross-Sectional Study.

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. 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. 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). 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.

Effect of Retro Walking Combined with Lagos Neuropathy Protocol on Balance and Spatiotemporal Parameters of Gait among Patients with Diabetic Neuropathy: A Prospective Interventional Study

Introduction: Diabetic Peripheral Neuropathy (DPN) clinically manifests as a sensorimotor disturbance that leads to complications in gait alteration and balance impairment. Balance and locomotion are the most critical aspects of an individual’s independence. Aim: To assess the effect of Retro walking with Lagos Neuropathy Protocol (LNP) on balance and spatiotemporal parameters of gait among patients with Diabetic neuropathy. Materials and Methods: The present prospective interventional Study was conducted in the Outpatient Department (OPD), Krupanidhi College of Physiotherapy, Bengaluru, Karnataka, India, from October 2022 to June 2023. The sample size was 60 individuals, 30 in each group (experimental and control group). Group 1, the control group, received the conventional LNP. Group 2, the experimental group, received the LNP combined with backward walking. The interventions were given to the patients four times/week for eight weeks. Subjects were assessed at the initial stage and following the end of the intervention. The parameters assessed were balance and spatiotemporal parameters of gait, in which balance was assessed by using the Mini Balance Evaluation Systems Test (Mini-BESTest) and gait speed using a 10 m walk test; other gait parameters cadence, step length, and stride length were measured individually using a stopwatch and inch tape. The statistical software used was Statistical Package for the Social Sciences (SPSS) software version 29.0, and the tests included were paired t-tests and independent t-tests for data analysis. Result: The mean±Standard Deviation (SD) age of the experimental group participants was 51±3.24 years, and the control group was 50.87±3.12 years. A significant improvement was seen in cadence, step length, stride length, gait speed, and balance in the control and experimental group (p-value&lt;0.001) Greater improvement was found in the experimental group when compared with the control group in all the outcome measures. Significant improvement was seen in all parameters in the experimental group when compared to the control group at post-test (p-value &lt;0.05). Conclusion: The study concluded that the LNP combined with backward walking had a significant positive effect on balance and spatiotemporal determinants of gait than the LNP alone among DPN patients.

Metabolomics in Pathogenic Pathways and Targeted Therapies for Diabetic Neuropathy: A Comprehensive Review

Introduction and objective: This literature review aims to provide an overview of the progress in metabolomic assessment in animal and cell models and in humans with diabetic neuropathy (DN). Methods: Metabolomics has emerged as an important approach for investigating, identifying, and describing biomarkers related to DN. None has yet been validated for use in clinical practice. Results: DN induced significant alterations in energy metabolism and carbohydrates, lipids, amino acids, peptides, and proteins. Several treatments for DN, evaluated using metabolomics, were proved to have promising results. Conclusions: The ideal metabolite or set of metabolites that could be used as biomarkers should identify patients with diabetes prone to develop DN or those prone to progress to severe forms of sensory loss, associated with risk of ulcerations and amputation. Another potential use of a metabolite might be as an indicator of treatment response in clinical trials using agents with potential disease-modifying properties.

The Association between Vitamin B12 Deficiency and Metformin Therapy in Libyan Diabetic Patients

Metformin is the first line treatment of diabetic hyperglycaemia. However, numerous studies have shown that long-term use of metformin can result in a vitamin B12 deficiency. In this study, we sought to assess the prevalence of vitamin B12 deficiency in diabetic patients taking metformin on a long-term basis as well as the association between vitamin B12 deficiency and diabetic neuropathy. Across sectional study was conducted on 143 Libyan diabetic patients attending endocrinology outpatient diabetic centre in Benghazi, who are on metformin for at least 6 months, and eligible to the inclusion criteria. Data on metformin intake and confounding variables were collected from questionnaires. Serum vitamin B12 levels were estimated, and vitamin B12 deficiency was defined as serum B12 less than 196pg/ml. Data analysis was performed using the statistical package for social sciences (SPSS) version 28. The study involved 143 patients, with a majority being women (50.3%) and men (49.7%). The mean duration of diabetes was 10.52 ± 7.260 years. The mean daily dose of metformin was 1435.42 ± 377.766 mg for females and 1495.77 ± 392.678 mg for males. The mean duration of metformin intake was 7.93 ± 5.859 years for females and 7.34 ± 5.780 years for males. The mean serum vitamin B12 level was 469.78 ± 233.477 pg/mL, with males having non-significantly higher levels than females. 59.2% of male patients had vitamin B12 levels ≤420 pg/mL, while 51.4% of female patients had levels ≤420 pg/mL. Nevertheless, no patient had a vitamin B12 deficit. No significant correlation was observed between serum vitamin B12 levels with metformin dose, duration of action, or patient characteristics. Despite the high prevalence of peripheral neuropathy (36.4%), there was no significant difference in B12 levels between patients with and without neuropathy.

Aspirin-triggered lipoxin A4 reduces neuropathic pain and anxiety-like behaviours in male diabetic rats: antinociceptive enhancement by cannabinoid receptor agonists.

Neuropathy is the most common complication of diabetes, leading to painful symptoms like hyperalgesia. Current treatments for diabetic painful neuropathy often prove inadequate, necessitating the exploration of new pharmacological approaches. Therefore, this study aimed to investigate the potential antinociceptive effect of aspirin-triggered lipoxin A4 (ATL), a specialized pro-resolving lipid mediator, when administered alone or in combination with cannabinoid agonists, to alleviate diabetic neuropathic pain. Mechanical hyperalgesia in the hindpaws of streptozotocin (STZ)-induced diabetic (DBT) rats was assessed using the electronic Von Frey test (VFT), before diabetes induction and for up to 32 days after STZ administration and intraperitoneal ATL (0.3, 1, 3, 10, or 30 ng/rat) treatment, alone or in combination with intrathecal CB1 or CB2 receptor agonists (ACEA or JWH-133, respectively; 10 or 30 μg/rat). The effect of ATL treatment on locomotor activity and anxious or depressive-like behaviors was also evaluated. In comparison to control normoglycemic rats, control DBT rats developed: 1) mechanical hyperalgesia; 2) increase in anxious and depressive-like behaviors. ATL treatment attenuated mechanical hyperalgesia in DBT rats both acutely (at 30ng) and cumulatively (at doses of 1, 3, 10, or 30ng), without compromising locomotor activity. The antinociceptive effect of ATL (at 1 or 3ng) was augmented when combined with ACEA or JWH-133 treatments (only at a dose of 30 μg/rat). While ATL treatment alone reduced anxious-like behavior in DBT rats, it did not affect depressive-like behavior. These findings underscore the therapeutic potential of ATL, in diabetic complications, suggesting a possible interaction with the endocannabinoid system.

Effectiveness of Roux-en-Y Gastric Bypass in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials.

This meta-analysis aimed to evaluate the effectiveness of Roux-en-Y gastric bypass (RYGB) in people living with type 2 diabetes mellitus (T2DM). A comprehensive search was conducted in the PubMed database up to January 2024. A random-effects model was used to calculate the pooled standard mean differences (SMDs) and odds ratios (ORs). Ten studies were included in our review. The RYGB group demonstrated significantly better outcomes compared to the non-surgical group in multiple measures. These included higher triple criteria compliance rates (OR 9.04, 95% CI 3.22-25.36), complete T2DM remission (OR 15.37, 95% CI 4.42-53.41), and partial T2DM remission (OR 11.49, 95% CI 3.57-37.03). Additionally, improvements were observed in glycated hemoglobin A1c (HbA1c) levels (SMD - 1.41, 95% CI - 2.22 to - 0.61), with HbA1c < 6.0% (OR 8.54, 95% CI 3.38-21.62) and HbA1c < 7.0% (OR 5.62, 95% CI 3.20-9.86). Fasting blood glucose (FBG) levels also showed improvement (SMD - 0.43, 95% CI - 0.71 to - 0.14), with a higher proportion achieving FBG < 100mg/dl (OR 11.83, 95% CI 4.75-29.43). Other notable outcomes included significant percentage of total weight loss (%TWL: SMD 1.88, 95% CI 1.39-2.37), reductions in body mass index (BMI: SMD - 2.28, 95% CI - 3.52 to - 1.04), and improvements in lipid profiles, including low-density lipoprotein (LDL) levels (SMD - 1.01, 95% CI - 1.91 to - 0.11) and LDL < 2.59mmol/L (OR 3.65, 95% CI 1.94-6.87). In addition, high-density lipoprotein (HDL) levels increased (SMD 1.30, 95% CI 0.55-2.05), while triglycerides (SMD - 1.11, 95% CI - 1.70 to - 0.52), systolic blood pressure (SBP: SMD - 0.38, 95% CI - 0.70 to - 0.06), and diastolic blood pressure (DBP: SMD - 0.41, 95% CI - 0.63 to - 0.18) decreased. A greater proportion of patients in the RYGB group achieved SBP < 130mmHg (OR 3.15, 95% CI 1.61-6.13). Moreover, reductions were noted in insulin use (OR 0.25, 95% CI 0.14-0.46), diabetes medication use (SMD - 1.95, 95% CI - 3.32 to - 0.57), and peripheral neuropathy (OR 0.13, 95% CI 0.02-0.79). However, no significant differences were observed in hypertension medication use or retinopathy between the two groups. RYGB was found to be effective in improving glycemic control, promoting weight loss, enhancing lipid profiles, and managing blood pressure. It also significantly reduced the need for postoperative diabetes medications and the incidence of diabetic peripheral neuropathy in people living with T2DM.

Unravelling pain in diabetic neuropathy patients: Exploring the relationship between perceived pain severity, lifestyle, and coping strategies mediated by self-focused attention and rumination: A cross-sectional study

Unravelling pain in diabetic neuropathy patients: Exploring the relationship between perceived pain severity, lifestyle, and coping strategies mediated by self-focused attention and rumination: A cross-sectional study

An update on botulinum toxin treatment of painful diabetic neuropathy, post-traumatic painful neuropathy/neuralgia, post-herpetic neuralgia and occipital neuralgia.

The literature in botulinum toxin treatment for painful diabetic neuropathy (PDN), post traumatic neuralgia (PTN), postherpetic neuralgia (PHN) and occipital neuralgia (ON) was reviewed up to Oct 1st, 2024. Using the efficacy criteria set forth by the Assessment and Guideline subcommittee of the American Academy of Neurology, the current levels of efficacy for these conditions could be designated as followings: PDN: B (probably effective, two class II study), PTN: A (effective, two class I studies); PHN: A (effective, two class I studies), ON: (undetermined due to lack of blinded investigations). Due to the small number of patients in these studies, proof of efficacy requires conduction of controlled and blinded studies in large cohorts of patients with longer follow ups. Future prospects of botulinum therapy for these pain disorders were discussed along with the advantages of this mode of treatment over the current modes of treatment.

Modulation of pain sensitivity by Ascl1- and Lhx6-dependent GABAergic neuronal function in streptozotocin diabetic mice.

Painful diabetic neuropathy commonly affects the peripheral nervous system in individuals with diabetes. However, the pathological processes and mechanisms underlying diabetic neuropathic pain remain unclear. We aimed to identify the overall profiles and screen for genes potentially involved in pain mechanisms using transcriptome analysis of the dorsal root ganglion of diabetic mice treated with streptozotocin (STZ). Using RNA sequencing, we identified differentially expressed genes between streptozotocin-treated diabetic mice and controls, focusing on altered GABAergic neuron-related genes and inflammatory pathways. Behavioral and molecular analyses revealed a marked reduction in GABAergic neuronal markers (GAD65, GAD67, VGAT) and increased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in the diabetic group compared with controls. Intrathecal administration of lentiviral vectors expressing transcription factors Ascl1 and Lhx6 reversed pain hypersensitivity and restored normal expression of GABAergic genes and inflammatory mediators. Protein-protein interaction network analysis revealed five key proteins influenced by Ascl1 and Lhx6 treatment, including those in the JunD/FosB/C-fos signaling pathway. These findings suggest that Ascl1 and Lhx6 mitigate diabetic neuropathic pain by modulating GABAergic neuronal function, pro-inflammatory responses, and pain-related channels (TRPV1, Nav1.7). These results provide a basis for developing transcription factor-based therapies targeting GABAergic neurons for diabetic neuropathic pain relief.