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Objective: Previous observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN. Methods: We conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables. Results: The IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity. Conclusion: Our study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a—known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 μM: 2221 ± 466 μm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusionsSmall fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change of intestinal bacterial population are assumed to be their pathogenesis, the effects of dietary nutrition have not been evaluated. The relationship between dietary nutrition intake and pain sensation was evaluated in the Japanese population.We conducted the Iwaki project, a population-based study recruiting 1,028 individuals, in 2018. The relationships between the pain threshold from intraepidermal electrical stimulation (PINT) and the amount of dietary nutrition evaluated by a brief-type self-administered diet history questionnaire were examined. The odds ratio was further explored after categorizing subjects based on low (< 63.7 μg/day), intermediate (63.7-159.2 μg/day), and high cryptoxanthin levels (> 159.2 μg/day).Univariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake even after adjustments for other nutritional intakes (ß = 0.107, p < 0.01). Multivariate logistic regression analysis revealed low and high cryptoxanthin intake as significant risk factors for abnormal PINT (≥ 0.20 mA). Multivariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake levels after adjustment for other clinically PINT-related factors (ß = 0.09, p < 0.01).Adequate intake of cryptoxanthin is recommended to maintain the pain threshold in the Japanese population. [ABSTRACT FROM AUTHOR]

Aims: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent‐onset diabetes. Here, we aimed to substantiate these findings in a population‐based KORA F4 study. Materials and Methods: In this cross‐sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut‐off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4). Results: After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16–3.41), MNSI > 3: 2.27 (1.26–4.09), and MNSI > 4: 4.78 (2.22–10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42–4.16), MNSI > 3: 3.46 (1.82–6.59), and MNSI > 4: 4.75 (2.15–10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups. Conclusions: The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy. [ABSTRACT FROM AUTHOR]

Introduction To evaluate the cross-over association of moderate-to-high-intensity interval-training (M-HIIT) and low-frequency pulsed-electromagnetic field therapy (LFPMT) on functional balance (FB) and ankle-brachial index (ABI) in patients with diabetic polyneuropathy (DPN). Methods Twenty-four participants with DPN, age 40–65 years, 0.6 < ABI ≤ 0.9, were randomly allocated into group A (n = 7) and received M-HIIT followed by LFPMT, group B (n = 9) and received LFPMT followed by M-HIIT, or group C ( n = 8) as the control group. Each of the LFPMT (15 Hz, 20 G, for 24 min) and the M-HIIT was provided twice weekly, for 4 weeks. Variables were evaluated pre and after 4 and 8 weeks. Results After 4 weeks, the FB significantly increased [by 9.08% ( p = 0.00) and by 6.82% ( p = 0.00)] and the ABI significantly increased [by 7.84% ( p = 0.01) and 12.57% ( p = 0.03)], while after 8 weeks, the FB significantly increased [by 13.03% ( p = 0.00) and 11.26% ( p = 00)] and the ABI significantly increased [by 10.05% ( p = 0.01) and 13.01% (p = 0.01)] in groups A and B, respectively. Significant differences existed between-groups after 4 weeks in the [FB ( p = 0.00) and ABI ( p = 0.02)], and after 8 weeks [FB ( p = 0.00) and ABI ( p = 0.01)]. Post-hoc comparisons revealed the FB most significantly increased ( p = 0.001) in group A, while the ABI more significantly increased ( p = 0.02) in group B. Conclusions Combined M-HIIT and LFPMT programs were effective in improving FB and ABI. Furthermore, starting the rehabilitation regimen with M-HIIT followed by LFPMT had a superior effect in improving the FB while starting the program with LFPMT followed by M-HIIT was more effective in improving the ABI in patients with DPN.

Recent decades have been marked by a rapid increase in the number of patients suffering from diabetes. The development and progression of complications of the disease have the greatest impact on the life prognosis of patients with diabetes mellitus. One of the common complications of diabetes mellitus is diabetic polyneuropathy. According to expert estimates, diabetic polyneuropathy develops in 50% of patients with diabetes mellitus and in 10–30% of patients in a prediabetic state. In domestic clinical recommendations and algorithms, the treatment of diabetic polyneuropathy is considered only in terms of drugs used to treat the painful form of diabetic polyneuropathy. In the recommendations of international experts, pathogenetically oriented pharmacotherapy (alpha-lipoic acid and benfotiamine) occupies an important place. As part of the review, we examined the use of B vitamins for the treatment of diabetic polyneuropathy. We searched for relevant sources in the PubMed and Scopus information databases, including the time period up to 12.04.2024. Experience with the use of B vitamins shows that their maximum effectiveness is achieved when they are used in combination, which is due to the complementary effect of each individual vitamin. The use of a combination of vitamins B1, B6 and B12 for diabetic polyneuropathy normalizes reflex reactions, helps eliminate sensitivity disorders, increases the speed of conduction along nerve fibers, and has a moderate analgesic effect.

AIM: to assess proliferation and migration of keratinocytes at the nonhealing edges of neuropathic wounds.MATERIALS AND METHODS: 25 patients with neuropathic ulcers and 5 patients without diabetes with decubitus were enrolled. Diabetic foot (DF) patients were underwent to standard treatment including debridement, atraumatic dressing, offloading, antibacterial therapy if it needs. Severity of peripheral neuropathy was assessed according to the NDS scale. Histo­logical (hematoxylin and eosin) and immunohistochemical (Ki-67 , α7nAChR markers) examination of wound edge were done during treatment (0, 10, 24 days).RESULTS: All patients have severe neuropathy according to NDSm (>8). The average size of DF ulcers before and on 10th day of treatment was of 4 cm2 and 2,5 cm2, respectively (p

Purpose: The aim of this systematic review is to evaluate the usefulness of sural nerve ultrasonography in diagnosing diabetes mellitus (DM) and diabetic polyneuropathy (DPN), the latter of which is a common long-term complication for diabetic patients that frequently involves the sural nerve. Methodology: A meta-analysis of the cross-sectional areas (CSAs) of sural nerves in healthy individuals and patients with diabetes mellitus based on a total of 32 ultrasonographic-based studies from 2015 to 2023 was performed. Sub-analyses were performed for factors such as geographical location and measurement site. Results: The meta-analysis showed that the mean CSA of the sural nerve was significantly larger in DM patients with DPN only compared to healthy individuals across all regions and when pooled together. An age-dependent increase in the CSA of healthy sural nerves is apparent when comparing the paediatric population with adults. Conclusion: Sural nerve ultrasonography can distinguish diabetic adults with DPN from healthy adults based on cross-sectional area measurement. Future studies are needed to clarify the relationships between other parameters, such as body metrics and age, with sural nerve CSAs. Cut-offs for DPN likely need to be specific for different geographical regions. [ABSTRACT FROM AUTHOR]

AbstractAutomated and early detection of diabetics with polyneuropathy in an ambulatory health monitoring setup may reduce the major risk factors for diabetic patients. Increased and localized plantar pressure associated with impaired pain and temperature is a combination of developing foot ulcers in subjects with polyneuropathy. Although many interesting research works have been reported in this area, most of them emphasize on signal acquisition process and plantar pressure distribution in the foot region. In this work, a machine learning assisted low complexity technique was developed using plantar pressure and temperature signals which will classify between diabetic polyneuropathy and healthy subjects. Principal component analysis (PCA) and maximum relevance minimum redundancy (mRMR) methods were used for feature extraction and selection respectively followed by k-NN classifier for binary classification. The proposed technique was evaluated with 100 min of publicly available annotated data from 43 subjects and provides blind test accuracy, sensitivity, precision, F1-score, and area under curve (AUC) of 99.58%, 99.50%, 99.44%, 99.47% and 99.56% respectively. A low resource hardware implementation in ARM v6 controller required an average memory usage of 81.2 kB and latency of 1.31 s to process 9 s pressure and temperature data collected from 16 sensor channels for each of the foot region. [ABSTRACT FROM AUTHOR]

Background. Predicting the effectiveness of rehabilitation in patients with diabetic polyneuropathy (DPN) and type 2 diabetes mellitus is of great importance in modern clinical practice. Given the prevalence of diabetes and its complications, including DPN, the development of predictive models will allow for personalized treatment approaches, optimization of rehabilitation programs, and improvement in the quality of life for patients. Integrating state-of-the-art data analysis methods and molecular-biological approaches into predictive models will contribute to the development of innovative rehabilitation strategies and improve treatment outcomes in this important patient population. The purpose of the study was to propose a multifactorial regression mathematical model for predicting the effectiveness of diabetic polyneuropathy rehabilitation. Materials and methods. Ninety-five patients with type 2 diabetes and DPN were examined to construct a predictive model of rehabilitation effectiveness using multiple regression analysis. The quality of the model was evaluated using the Nagelkerke criterion (R²). Results. The analysis revealed several significant associations between various factors and the effectiveness of rehabilitation in DPN patients. Specifically, an increase in age was associated with a predicted decrease in rehabilitation effectiveness by 0.103. Moreover, each increase in the duration of diabetes mellitus was associated with an expected decrease in rehabilitation effectiveness, ranging from 1.341 to 3.732 depending on the duration range. Similarly, changes in tobacco smoking, employment status, body mass index, glycated hemoglobin levels, mobility, self-care, usual activities, pain/discomfort, anxiety/depression, sensory sensitivities, DN4 scores, and lipid profile were all significantly associated with variations in rehabilitation effectiveness. The regression model demonstrated high explanatory power, with an observed correlation coefficient (rxy) of 0.997, indicating a strong functional relationship. Furthermore, the model was statistically significant (p < 0.001), suggesting that the identified predictors collectively explain 99.5 % of the observed variance in rehabilitation effectiveness. These findings underscore the importance of considering multiple factors when predicting rehabilitation outcomes in DPN patients and highlight the potential utility of the developed model in clinical practice. Conclusions. The proposed mathematical model for predicting the effectiveness of rehabilitation in type 2 diabetes patients with DPN demonstrates high acceptability, quality, and effectiveness. The application of this model, considering 99.5 % of DPN factors, will enhance the accuracy and timeliness of rehabilitation, improve treatment outcomes, facilitate regular monitoring of patients at high risk of complications, promote the development of informational leaflets and adapted programs for DPN prevention in type 2 diabetes patients, and facilitate the creation of relevant medical calculators and informational systems. [ABSTRACT FROM AUTHOR]

Objective: To assess the role of serum neurofilament light chain (NfL) levels in individuals with diabetic polyneuropathy (DPN) compared with controls, as well as to highlight the different sonographic changes in DPN and determine if NfL correlates with sonographic, clinical, and functional parameters. Methods: Diabetic individuals with signs or symptoms consistent with peripheral nerve involvement were recruited. They were evaluated by examination, functional neuropathy severity scores, laboratory assessments (including NfL), nerve conduction studies (NCS), and ultrasound. Ultrasound was performed of the bilateral median, ulnar, tibial, fibular, sural, and vagus nerves, and cervical roots 5 and 6. Results were compared with age, sex, and body mass index matched healthy controls. Results: A total of 320 nerves from 20 patients and 480 nerves from 30 controls were evaluated. NfL was significantly elevated in those with diabetes with a mean and standard deviation of 6.95 ± 2.95 pg/mL in the diabetic group and 2.83 ± 0.77 pg/mL in controls (P <.001). Nerve cross‐sectional area and serum NfL levels correlated significantly with clinical and functional parameters and with each other (P <.05). Conclusion: Individuals with DPN have significantly higher NfL levels than healthy controls, and NfL levels correlate with ultrasonographic parameters. These findings may be useful for the diagnosis, prognosis, and disease monitoring of those with DPN, though further exploration is needed. [ABSTRACT FROM AUTHOR]

Introduction. To evaluate the cross-over association of moderate-to-high-intensity interval-training (M-HiiT) and low-frequency pulsed-electromagnetic field therapy (LFPMT) on functional balance (FB) and ankle-brachial index (ABi) in patients with diabetic polyneuropathy (dPN). Methods. Twenty-four participants with dPN, age 40--65 years, 0.6 ≤ ABi 0.9, were randomly allocated into group A (n = 7) and received M-HIIT followed by LFPMT, group B (n = 9) and received LFPMT followed by M-HIIT, or group C (n = 8) as the control group. Each of the LFPMT (15 Hz, 20 G, for 24 min) and the M-HIIT was provided twice weekly, for 4 weeks. Variables were evaluated pre and after 4 and 8 weeks. Results. After 4 weeks, the FB significantly increased [by 9.08% (p = 0.00) and by 6.82% (p = 0.00)] and the ABi significantly increased [by 7.84% (p = 0.01) and 12.57% (p = 0.03)], while after 8 weeks, the FB significantly increased [by 13.03% (p = 0.00) and 11.26% (p = 00)] and the ABi significantly increased [by 10.05% (p = 0.01) and 13.01% (p = 0.01)] in groups A and B, respectively. Significant differences existed between-groups after 4 weeks in the [FB (p = 0.00) and ABi (p = 0.02)], and after 8 weeks [FB (p = 0.00) and ABi (p = 0.01)]. Post-hoc comparisons revealed the FB most significantly increased (p = 0.001) in group A, while the ABi more significantly increased (p = 0.02) in group B. Conclusions. Combined M-HIIT and LFPMT programs were effective in improving FB and ABi. Furthermore, starting the rehabilitation regimen with M-HiiT followed by LFPMT had a superior effect in improving the FB while starting the program with LFPMT followed by M-HIIT was more effective in improving the ABi in patients with DPN. [ABSTRACT FROM AUTHOR]

Simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), muscular and epidural blocks are most often prescribed to relieve acute pain. However, the use of a number of drugs is associated with the development of unwanted side effects. Furthermore, in some cases the need for both symptomatic and pathogenetic therapy necessitates the prescription of combination treatment involving drugs that exert metabolic effects. The paper discusses the role of metabolic therapy in patients with pain syndrome exemplified by the drugs containing B vitamins. Emphasis is placed on the two-step therapy of pain syndrome.

Abstract Background Early diagnosis of diabetic polyneuropathy (DPN) can significantly improve the prognosis and help prevent severe complications. The aim of this work was to study clinical, radiological, laboratory and neurophysiological findings for early detection of peripheral neuropathy in T2DM. Methods A total of 60 diabetic patients were classified according to Toronto Clinical Neuropathy Score (TCNS) into: Group 1: 20 diabetic patients with no evident neuropathy. Group 2: 20 diabetic patients with mild neuropathy. Group 3: 20 diabetic patients with moderate and severe neuropathy. All patients underwent a neurological examination, nerve conduction studies and optical coherence tomography (OCT) to assess retinal nerve fiber layer (RNFL) thickness. Additionally, ELISA technique to measure serum interleukin-6 (IL-6). Results The analysis of gender and age distributions among the groups revealed no significant differences. There were statistically significant differences regarding disease duration, HBA1c, body mass index Systolic and diastolic blood pressure. Group 3 had such significant impairment that resulted in an inability to record the measurements of sural nerves. The study's statistical analysis results for OCT variables, and post hoc comparisons revealed significant differences between all three groups. The results demonstrated significant variations in Serum IL6 levels among the groups, with Group 3 having the highest IL6 levels. In groups 1, 2, and 3 the area under the curve for IL-6 and RNFL showed a good differentiation ability between groups. Conclusion We conclude that the total thickness RNFL and serum IL-6 levels are a potential biomarker in prediction the severity of DPN.

This study aimed to determine the efficacy of assessing the severity of diabetic polyneuropathy (DPN) in patients with untreated diabetes. Seventy-two patients with untreated type 2 diabetes who were hospitalized for glycemic control were enrolled and divided into the following two groups: patients who had no prior diagnosis and patients who were unattended or had discontinued treatment. Electrophysiological criteria consistent with Baba's classification were used to diagnose and assess the severity of DPN. The patients were divided into three subgroups: no DPN (stage 0), mild DPN (stage 1), and moderate or more-severe DPN (stages 2-4). Intergroup comparisons were performed for the clinical characteristics and the results of the nerve conduction studies. Twenty-two (30%), 25 (35%), and 25 (35%) patients were categorized into the no DPN, mild DPN, and moderate or more-severe DPN subgroups, respectively. The number of patients who were unattended or had discontinued treatment in the moderate or more-severe DPN subgroup was significantly higher than that in the no DPN subgroup. The patients in the moderate or more-severe DPN subgroup had an increased risk of developing diabetic retinopathy and nephropathy, with odds ratios of 19.5 and 11.0 for advanced stages of retinopathy and nephropathy, respectively. Thus, the assessment of the severity of DPN could aid in the prediction of the risk of developing diabetic complications in patients with untreated diabetes. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is a fat-soluble vitamin that prevents cardiovascular diseases and diabetes mellitus (DM). The present research aimed to study the impact of 25-hydroxyvitamin D (25(OH)D) level on the health status of patients with type 2 DM (T2DM) hospitalized in the "Pius Brînzeu" Emergency Clinical County University Hospital in Timisoara, Romania. Methods: The study retrospectively included 160 patients with T2DM who were clinically and biologically evaluated during hospitalization. Results: 13.1% of patients had optimal, 23.1% insufficient, and 63.8% deficient 25(OH)D values. Patients with 25(OH)D deficiency presented poorer glycemic control and were older, with higher weight, but had altered renal function, anemia, and lower iron values. Also, patients with associated neoplasia, diabetic neuropathy, cardiovascular disease (CVD), dementia, and grade 3 arterial hypertension (HTN) had lower values of 25(OH)D. An age > 55 years (sensitivity 69.9, specificity 82.5, AUROC 0.786, p < 0.001) and an HbA1c > 7.7% (sensitivity 89.3, specificity 92.9, AUROC 0.938, p < 0.001) predict 25(OH)D deficiency in T2DM patients. Conclusions: Vitamin D influences almost every system and organ in the body, so it should be a routine test for all patients with DM to correct the deficiency and prevent other diseases and complications. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of diabetic polyneuropathy (DPN) can significantly improve the prognosis and help prevent severe complications. The aim of this work was to study clinical, radiological, laboratory and neurophysiological findings for early detection of peripheral neuropathy in T2DM. Methods: A total of 60 diabetic patients were classified according to Toronto Clinical Neuropathy Score (TCNS) into: Group 1: 20 diabetic patients with no evident neuropathy. Group 2: 20 diabetic patients with mild neuropathy. Group 3: 20 diabetic patients with moderate and severe neuropathy. All patients underwent a neurological examination, nerve conduction studies and optical coherence tomography (OCT) to assess retinal nerve fiber layer (RNFL) thickness. Additionally, ELISA technique to measure serum interleukin-6 (IL-6). Results: The analysis of gender and age distributions among the groups revealed no significant differences. There were statistically significant differences regarding disease duration, HBA1c, body mass index Systolic and diastolic blood pressure. Group 3 had such significant impairment that resulted in an inability to record the measurements of sural nerves. The study's statistical analysis results for OCT variables, and post hoc comparisons revealed significant differences between all three groups. The results demonstrated significant variations in Serum IL6 levels among the groups, with Group 3 having the highest IL6 levels. In groups 1, 2, and 3 the area under the curve for IL-6 and RNFL showed a good differentiation ability between groups. Conclusion: We conclude that the total thickness RNFL and serum IL-6 levels are a potential biomarker in prediction the severity of DPN. [ABSTRACT FROM AUTHOR]

Background: Diabetic polyneuropathy (DPN) is relatively common complication of long-term diabetes and is thought to be progressive and irreversible. The loss of sensations associated with Diabetic polyneuropathy is thought to contribute to impaired balance and increased risk of falling. Reduced toe flexor strength is an independent predictor of falls. However, it is unknown whether strengthening programs can restore toe flexor strength in patients with DPN. The aim of this study was to investigate whether a progressive resistance training program, focused specifically on the foot & toe flexor muscles, could improve toe flexor strength in patients with DPN. Methods: A total of 20 patients were allocated into two groups of 10 each. Group A receive 12 sessions of (Conventional physiotherapy & Modified toe training programme) and Group B (Conventional physiotherapy & General toe exercise). Berg balance score (BBS), Fall efficacy scale international (FES-I) & Time up and go test (TUG) were measured on first day (Week 1) and last day (Week 4) of intervention. Pre-test and post-test scores were compared and results were tabulated. Result: Both groups showed significant improvement in balance performance. The Group A showed statistically significant improvement in static & functional balance when compared to Group B. Conclusion:The study demonstrated a significant improvement in balance and functional mobility was seen among Group A. [ABSTRACT FROM AUTHOR]

Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a—known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 μM: 2221 ± 466 μm, control: 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities.

Aims/hypothesis: Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes. Methods: Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres. Results: There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures. Conclusions/interpretation: Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim. This study aimed to determine the association between vestibular dysfunction, falls, and postural instability in individuals with type 2 diabetes (T2D) compared to healthy control individuals and to examine the impact of diabetic polyneuropathy (DPN). Methods. This cross-sectional study included individuals with T2D with DPN (nD43), without DPN (nD32), and healthy controls (nD32). Cervical and ocular vestibular evoked myogenic potentials (VEMP) were recorded, and latencies and amplitudes were determined. DPN was diagnosed based on nerve conduction studies and clinical scores. Postural instability was examined using a static posturographic balance system and calculated as an instability index (ST). Falls were recorded retrospectively during the past year. Group comparisons were conducted by using univariate and bivariate statistics. Results. Individuals with T2D experienced more falls than healthy controls (T2D with DPN n=12[38%], T2D without DPN n=15[35%], controls n=5[16%], p=0:04). Individuals with T2D had decreased postural stability, T2D with DPN, ST (median of 52[iqi = 33; 77]), T2D without DPN, ST (median of 31[iqi = 24; 39]), controls ST (median of 26[iqi = 19; 33], p=0:01), when comparing all three groups. Individuals with T2D had a greater number of no-responses in oVEMP compared to controls (T2D with DPN, n=15[46.9%] T2D without DPN n=25[58.1%], controls n=9[28.1%], p=0:04). No difference was found in cVEMP and oVEMP amplitudes in any of the groups. Irrespectively of DPN, fallers with T2D had decreased oVEMP and cVEMP latencies on the right ears, when comparing to non-fallers, respectively, n10 (fallers [median of 16, iqi=15;19 ms.] vs. non-fallers [median of 25 iqi=16;35 ms]); p13 (fallers [median of 16, iqi=15;17 ms.] vs. non-fallers [median of 15, iqi=8;16 ms.], p<0:05). Conclusion. Falls and postural instability were more frequent in individuals with T2D compared to healthy controls. Fallers with T2D had vestibular end-organ impairments based on the oVEMP and cVEMP latencies on the right but not the left ears, irrespective of DPN. Individuals with T2D had more frequent no-response of the oVEMP, indicating impaired vestibular nerve function. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to access whether a personal attitude to physical activity (PA) may influence the appearance of diabetic polyneuropathy (DPN) patients with well-controlled type 1 diabetes mellitus. Methods: Ninety patients attending the diabetes technology outpatient clinic were enrolled. DPN was investigated according to the Toronto consensus diagnostic criteria. PA was assessed using the International Physical Activity Questionnaire. Results: PA was low in 21.1%, moderate in 42.2% and high in 36.7% of patients. According to Toronto criteria, we defined two categories: the first one with DPN absent or possible (57 (63.3%)) and a second one with DPN certain or probable (33 (36.7%)). The χ2-test of the PA groups and the DPN categories showed a statistically significant difference (p < 0.001), with less neuropathy in patients belonging to the group of moderate/high PA. Exposure to a minimum of 600 MET minutes/week was protective factor against the onset of DPN (odd ratio 0.221, c.i. 0.068–0.720, p = 0.012). Conclusions: This study suggests that DPN is less present in type 1 diabetic patients with good metabolic control and a good personal habit of PA. Moderate-to-vigorous PA of at least 600 MET minutes/week might be a protective factor against DPN. [ABSTRACT FROM AUTHOR]

Background The nociceptive flexion reflex (NFR) is a polysynaptic and multisegmental spinal reflex that develops in response to a noxious stimulus and is characterized by the withdrawal of the affected body part. The NFR possesses two excitatory components: early RII and late RIII. Late RIII is derived from high-threshold cutaneous afferent A-delta fibers, which are prone to injury early in the course of diabetes mellitus (DM) and may lead to neuropathic pain. We investigated NFR in patients with DM with different types of polyneuropathies to analyze the role of NFR in small fiber neuropathy (SFN). Methods We included 37 patients with DM and 20 healthy participants of similar age and sex. We performed the Composite Autonomic Neuropathy Scale-31, modified Toronto Neuropathy Scale, and routine nerve conduction studies. We grouped the patients into large fiber neuropathy (LFN), SFN, and no overt neurological symptom/sign groups. In all participants, NFR was recorded on anterior tibial (AT) and biceps femoris (BF) muscles after train stimuli on the sole of the foot, and NFR-RIII findings were compared. Results We identified 11 patients with LFN, 15 with SFN, and 11 with no overt neurological symptoms or signs. The RIII response on the AT was absent in 22 (60%) patients with DM and 8 (40%) healthy participants. The RIII response on the BF was absent in 31 (73.8%) patients and 7 (35%) healthy participants (P  = .001). In DM, the latency of RIII was prolonged, and the magnitude was reduced. Abnormal findings were seen in all subgroups; however, they were more prominent in patients with LFN compared to other groups. Conclusions The NFR-RIII was abnormal in patients with DM even before the emergence of the neuropathic symptoms. The pattern of involvement before neuropathic symptoms was possibly related to an earlier loss of A-delta fibers. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. Methods: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as “healthy” and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. Results: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, “sensory loss” was most strongly associated with PN development (adjusted HR, 4.35; P = .011). Conclusion: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development. [ABSTRACT FROM AUTHOR]

Objectives. To study the efficacy of the drug Cytoflavin in patients with diabetic polyneuropathy (DPN) by assessing the blood tumor necrosis factor-α (TNF-α) concentration. Materials and methods. An open, comparative, prospective observation of patients with a history of DPN for more than five years and high blood TNF-α levels was carried out. All patients received basic oral combined hypoglycemic therapy; patients in group 1 received Cytoflavin (10 ml per 200 ml 0.9% sodium chloride i.v.) for 10 days, followed by switching to oral Cytoflavin, 2 tablets twice a day for one month. The main indication for the use of Cytoflavin was the presence of cerebrovascular disease in all the patients studied. The severity of the clinical manifestations of DPN and patients' quality of life (QoL) were assessed, and TNF-α levels were determined as an indicator of inflammation. Results. Cytoflavin use was associated with increases in quality of life indicators, decreases in the severity of sensory disturbances, and decreases in TNF-α levels, which may indicate a possible anti-inflammatory mechanism of action for this drug. Conclusions. Use of Cytoflavin can inhibit inflammation and reduce the severity of sensory disorders in patients with DPN. [ABSTRACT FROM AUTHOR]

Introduction: Carpal tunnel syndrome (CTS) is more common in diabetes mellitus (DM), especially in individuals with diabetic polyneuropathy (DPN). This study aimed to retrospectively investigate the effects of elevated glycosylated hemoglobin (HbA1c) levels, duration of diabetes, and other microvascular complications of DM on the frequency and severity of CTS in patients with DPN. Material and methods: 124 DPN patients were included in the study. In these patients, fasting blood glucose (FBG) and HbA1c levels, duration of DM, antidiabetic drugs used, comorbidities, and other complications of diabetes were questioned. According to the results of the electrophysiological examination, the patients were divided into 2 groups: those with only DPN and those with DPN + CTS. Results: When diabetes complications were investigated, diabetic nephropathy was found only in those with DPN + CTS (p=0.045). Electrophysiologically, in sensory fibers in all patients, In 43 patients (34.7%), involvement of motor fibers was accompanied. A positive correlation was found between the severity of CTS and duration of diabetes, FBG and HbA1c levels, and subcutaneous insulin use (p=0.018, p=0.014, p=0.003, p=0.029, respectively). Conclusion: Good glycemic control can reduce the risk of developing CTS with microvascular complications of diabetes. Therefore, it is important for patients to protect their hand function and prevent the development of CTS by being informed about the complications of diabetes.

Introduction: Peripheral sensorimotor polyneuropathy is present in nearly half of the patients diagnosed with diabetes mellitus. Over the past 10 years, animal and human studies have suggested that vitamin D3 treatment may have a role in preventing or reducing neuropathic complaints and symptoms.

Purpose Neurodynamic mobilization is a set of passive or active movements aimed at restoring the neural system’s ability to bear the normal compressive, friction, and tensile stresses encountered in daily life. This study aimed to investigate the effect of neurodynamic mobilization on sensory and motor nerve conduction studies, pain, and functional activity in patients with type 2 diabetic neuropathy (DN). Methods A total of 42 patients were randomly assigned to the neurodynamic mobilization group (NMG) or selected therapy program group (STPG). Electrophysiological measurements for median sensory and tibial motor nerve conduction velocity, and functional activity were conducted using the Katz Index of Independence, while pain was evaluated using the visual analogue scale. Results Improvement was noted in the post-treatment median sensory ( p = 0.002) and tibial motor ( p < 0.001) nerve conduction velocity, functional activity ( p < 0.001), and pain ( p < 0.001), and a statistically significant difference was demonstrated for the NMG, but not for the STPG. Conclusions Neurodynamic mobilization improved the sensory and motor nerve conduction velocity, functional activity, and pain in patients with type 2 DN.

BACKGROUND: Diabetes mellitus, one of the most common chronic diseases in the world, has a significant aggravating effect on the course of myocardial infarction. Thioctic acid affects the cardiovascular risks of diabetes mellitus and has a protective effect on ischemic myocardium. Human studies to support this effect have not been widely conducted.AIM: To confirm the possibility of using thioctic acid in patients with diabetes mellitus or newly diagnosed diabetes mellitus in combination with diabetic polyneuropathy who have had anterior septal Q wave myocardial infarction to prevent hypertrophy and myocardial remodeling.MATERIALS AND METHODS: The study involved patients with myocardial infarction and type 2 diabetes mellitus, newly diagnosed diabetes mellitus and diabetic polyneuropathy. From the obtained groups, by randomization, subgroups were allocated to which thioctic acid was prescribed at a dosage of 600 mg / day orally for 3 months. To determine the comparability of the groups, a standard set of stationary studies was carried out. At the initial stage and 12 months after the start of the study, the echocardiographic parameters of myocardial hypertrophy and remodeling were monitored.RESULTS: The study involved 125 people, 5 people were excluded due to the development of unwanted adverse reactions. The formed groups were comparable in terms of initial parameters. In the main subgroups, statistically significant dynamics of LV wall hypertrophy and myocardial remodeling were not revealed. In the control subgroup of patients with diabetes mellitus, an increase in the thickness of the IVS was noted by 0.67 mm [95% CI: 0.4–0.94, p = 0.021], LVTZ by 0.8 mm [95% CI: 0.43–1 , 27, p = 0.043], LVMI at 9.2 g / m2 [95% CI: 6.15–12.24, p = 0.05], LVMI at 17.8 g. [95% CI: 11.3–24.3, p = 0.011], an increase in the prevalence of concentric myocardial remodeling by 16.7% (p = 0.026). In the control subgroup of patients with newly diagnosed diabetes mellitus, an increase in the thickness of the IVS was noted by 0.83 mm 95% [CI: 0.43–1.23, p = 0.047], LVMI by 7.9 g / m2 [95% CI: 4 , 47–11.43, p = 0.033], LVM at 16.7 gr. [95% CI: 9.75–23.65, p = 0.023], an increase in the prevalence of concentric myocardial remodeling by 16.7% (p = 0.026). In the main subgroup of patients with diabetes mellitus, a decrease in LVMM by 3.33 g was noted. [95% CI: 1.94–4.72, p = 0.024], LVMI at 4.19 g / m2 [95% CI: 2.18–6.2, p = 0.047].CONCLUSION: The use of thioctic acid on the 3rd day from antero-septal Q wave myocardial infarction in patients with type 2 diabetes, newly diagnosed diabetes mellitus, in combination with diabetic polyneuropathy, at a dosage of 600 mg / day orally, prevents hypertrophy and myocardial remodeling, and also contributes to the positive dynamics of the structure of the ejection fraction.

Aim This study aimed to determine the association between vestibular dysfunction, falls, and postural instability in individuals with type 2 diabetes (T2D) compared to healthy control individuals and to examine the impact of diabetic polyneuropathy (DPN). Methods This cross-sectional study included individuals with T2D with DPN (n = 43), without DPN (n = 32), and healthy controls (n = 32). Cervical and ocular vestibular evoked myogenic potentials (VEMP) were recorded, and latencies and amplitudes were determined. DPN was diagnosed based on nerve conduction studies and clinical scores. Postural instability was examined using a static posturographic balance system and calculated as an instability index (ST). Falls were recorded retrospectively during the past year. Group comparisons were conducted by using univariate and bivariate statistics. Results Individuals with T2D experienced more falls than healthy controls (T2D with DPN n = 12[38%], T2D without DPN n = 15[35%], controls n = 5[16%], p = 0.04). Individuals with T2D had decreased postural stability, T2D with DPN, ST (median of 52[iqi = 33; 77]), T2D without DPN, ST (median of 31[iqi = 24; 39]), controls ST (median of 26[iqi = 19; 33], p = 0.01), when comparing all three groups. Individuals with T2D had a greater number of no-responses in oVEMP compared to controls (T2D with DPN, n = 15[46.9%] T2D without DPN n = 25[58.1%], controls n = 9[28.1%], p = 0.04). No difference was found in cVEMP and oVEMP amplitudes in any of the groups. Irrespectively of DPN, fallers with T2D had decreased oVEMP and cVEMP latencies on the right ears, when comparing to non-fallers, respectively, n10 (fallers [median of 16, iqi=15;19 ms.] vs. non-fallers [median of 25 iqi=16;35 ms]); p13 (fallers [median of 16, iqi=15;17 ms.] vs. non-fallers [median of 15, iqi=8;16 ms.], p

Background: peripheral arterial disease (PAD) is identified late in diabetic patients because, in the majority of cases, it is associated with diabetic peripheral neuropathy, resulting in little or no symptoms, or symptoms that are completely neglected. Methods: In this study were enrolled all patients over 18 years of age, with diabetes mellitus type II for more than a year with poor glycemic control, diagnosed with diabetic polyneuropathy admitted to the Diabetology Department, Emergency County Hospital of Targu Mures, Romania between January 2020 and March 2023. We divided the patients into two groups, based on the presence or absence of subclinical atherosclerosis in the lower limb, named "SA" and "non-SA". Results: Patients in the SA group were older (p = 0.01) and had a higher incidence of IHD (p = 0.03), history of MI (p = 0.02), and diabetic nephropathy (p = 0.01). Moreover, patients with subclinical atherosclerosis had a higher BMI (p < 0.0001) and a longer duration of diabetes (p < 0.0001). Among all patients, the systemic inflammatory markers, MLR (r = 0.331, p < 0.001), NLR (r = 0.517, p < 0.001), PLR (r = 0.296, p < 0.001), SII (r = 0.413, p < 0.001), as well as BMI (r = 0.241, p < 0.001) and HbA1C (r = 0.489, p < 0.001), demonstrated a strong positive correlation with the diabetes duration. The multivariate logistic regression analysis showed that older patients (OR: 2.58, p < 0.001), the male gender (OR: 2.30, p = 0.006), a higher baseline levels of BMI (OR: 7.71, p < 0.001), and the duration of diabetes (OR: 8.65, p < 0.001) are predictors of subclinical atherosclerosis in DN patients. Additionally, the high baseline levels of all systemic inflammatory markers (for all: p < 0.001) and poor diabetes management (OR: 10.4, p < 0.001 for HbA1C; OR: 10.78, p < 0.001 for admission glucose) are independent predictors of SA. Conclusions: the inflammatory markers, NLR, MLR, PLR, and SII, being cheap and easy to collect in routine medical practice from the standard blood tests, could be an important step in predicting vascular outcomes in diabetic patients and the disease's progression, playing a key role in follow-up visits in type-2 diabetic patients and PAD patients. [ABSTRACT FROM AUTHOR]