Search Results (84)

Background: Peripheral neuropathy (PN) refers to a spectrum of symptoms resulting from dysfunctions of the peripheral sensory, motor, and autonomic neurons. PN is associated with significant balance impairments and an increased risk of falls, contributing to reduced functional independence and quality of life. Although diabetic PN has been extensively investigated, there remains a lack of synthesized evidence regarding rehabilitation approaches for individuals with non-diabetic PN. This systematic review aims to evaluate the effectiveness of stabilometric platforms incorporating virtual reality (VR) and feedback (FB) in improving balance and related outcomes in patients with PN of various etiologies. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the protocol registered in PROSPERO (CRD420251086625). Seven major databases (PubMed, Scopus, ScienceDirect, Cochrane, Web of Science, Springer, and Wiley) were searched from inception to April 2025. Studies including adult patients with non-diabetic PN undergoing balance rehabilitation using stabilometric platforms with VR and FB were considered. The methodological quality of the included studies was assessed using the PEDro scale, RoB2, and ROBINS-I V2 tools. Results: A total of six studies met the inclusion criteria, encompassing 133 participants with non-diabetic PN. Interventions involving specialized balance training platforms incorporating VR and FB demonstrated significant improvements in both static and dynamic balance and postural control, as well as a reduction in the risk of falling. These systems also showed favorable adherence rates to rehabilitation programs. However, variability in intervention protocols and outcome measures limited the ability to perform direct comparisons across studies. Conclusions: The use of stabilometric platforms appears to be a promising approach for balance rehabilitation in patients with non-diabetic PN. Despite the limited number of included studies, the results support their integration into rehabilitation programs for this patient population. Further large-scale, high-quality studies are needed to establish standardized protocols and confirm long-term efficacy. Full article

Background: Diabetes often causes microvascular complications such as neuropathy. Autonomic neuropathy remains under-recognized, and its impact on quality of life (QoL) is unclear. This study investigated associations between symptoms of autonomic dysfunction, including organ-specific subdomains, and QoL in individuals with type 1 (T1D) and type 2 diabetes (T2D). Methods: A cross-sectional population-based survey was conducted in the North Denmark Region among individuals with T1D and T2D, assessing autonomic symptom burden with the Composite Autonomic Symptom Score-31 (COMPASS-31), general well-being with the Short Form Health Survey (SF-36), and psychological well-being with the Hospital Anxiety and Depression Scale. Multivariate linear regression assessed associations between autonomic symptom scores and QoL outcomes. Results: The COMPASS-31 scores were 8.9 (2.9; 22.8) in T1D and 12.4 (5.3; 26.1) in T2D. SF-36 physical composite scores were 52.1 (43.2; 56.4) in T1D and 49.3 (40.3; 54.8) in T2D, with similar mental composite scores (50.7 (40.3; 56.9) vs. 51.4 (41.2; 57.2)). Signs of moderate to severe anxiety were observed in 9.9% (95% confidence interval (CI): 8.1–11.9) of T1D and 8.9% (95% CI: 8.1–9.6) of T2D, while depression was present in 5.9% (95% CI: 4.5–7.6) and 5.1% (95% CI: 4.5–5.7). Higher autonomic symptom burden, especially pupillary, vasomotor, and bladder domains, was associated with lower SF-36 score and higher anxiety and depression scores. Conclusions: the Autonomic symptom burden is associated with reduced QoL and increased psychological distress in individuals with diabetes. These findings emphasize the importance of assessing and managing autonomic symptoms in diabetes care to support overall well-being. Full article

Background/Objectives: Cardiac autonomic neuropathy (CAN) is a common but also underdiagnosed complication of diabetes mellitus (DM), associated with high cardiovascular risk and mortality. Sudomotor dysfunction can serve as an early indicator of autonomic dysfunction. This study evaluated the association between sudomotor dysfunction and the severity of CAN in patients with type 2 diabetes (T2D). Methods: In this cross-sectional study, 109 patients with T2D were evaluated for diabetic peripheral neuropathy, cardiovascular autonomic dysfunction, and sudomotor dysfunction. Additionally, clinical and biochemical data were collected from patients’ medical records. Results: Sudomotor dysfunction (SUDO+) was present in 59.6% of patients. The presence of SUDO+ was associated with a higher age, longer duration of diabetes, lower eGFR (estimated glomerular filtration rate) values, and more severe signs of peripheral neuropathy. SUDO+ patients showed significantly greater orthostatic systolic and diastolic BP (blood pressure) changes, lower RR interval ratios, and lower feet ESC (electrochemical skin conductance) values. ROC (receiver operating characteristic) analysis for feet ESC in identifying pathological RR ratio showed an AUC of 0.689 (95% CI: 0.593–0.774, p = 0.0022), with a sensitivity of 46.7% and a specificity of 94.7% at a cutoff of ≤68 µS. For orthostatic hypotension and QTc prolongation, the ESC values had limited discriminative power. Chi-squared analysis showed a significant association between feet sudomotor impairment and pathological RR ratio (χ² = 6.521, p = 0.0107). Conclusions: Sudomotor dysfunction is associated with indicators of CAN. SUDOSCAN can be used as a complementary tool for early CAN detection in clinical practice. Full article

Background/Objectives: Diabetic neuropathy (DN) is one of the most common and disabling complications of diabetes mellitus (DM), affecting motor, sensory, and autonomic nerves. Genetic factors, particularly polymorphisms in the Angiotensin-converting enzyme (ACE) gene, have been proposed as contributors to DN susceptibility. This study aimed to synthesize the scientific evidence on ACE gene polymorphisms and their association with DN through a scoping review combined with scientometric analysis. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was performed in February 2025, following JBI and PRISMA-ScR guidelines. Observational studies involving individuals with DN and the genotyping of ACE polymorphisms were included. Scientometric mapping was conducted using the Bibliometrix package in RStudio to identify publication trends and key thematic terms. Results: From 100 screened articles, 11 met the inclusion criteria. Most studies (72.7%) addressed diabetic peripheral neuropathy, while 27.3% investigated cardiac autonomic neuropathy. All studies analyzed the I/D polymorphism in intron 16 of the ACE gene. The D allele and DD genotype were associated with increased susceptibility to DN in over half of the studies (6/11), while the II genotype was reported as protective in 3/11. Findings varied by ethnicity and study design. The scientometric analysis identified ‘peripheral diabetic neuropathy’, type 2 diabetes’, and ‘ACE gene polymorphism’ as the most frequently co-occurring terms, indicating that research on this topic has been concentrated around these themes, while showing limited diversity in geographic origin and scope. Conclusions: ACE I/D polymorphism appears to modulate susceptibility to DN, though interethnic variability and methodological heterogeneity challenge definitive conclusions. Broader, standardized studies are needed to validate its utility as a predictive biomarker. Full article

Peripheral and autonomic neuropathy are common in type 2 diabetes; they are associated with oxidative stress and inflammation. Cocoa, rich in polyphenols, may offer neuroprotective benefits. This study evaluated the effect of cocoa supplementation on the biochemical, clinical, and somatosensory profile of neuropathy in individuals with type 2 diabetes. A 12-week, double-blind controlled trial involved 39 subjects randomized to receive cocoa capsules (50 mg polyphenols) or placebo (methylcellulose). Evaluations included glycemic and lipid profiles, neutrophil/lymphocyte ratio, blood pressure, standardized questionnaires, anthropometric measurements, and the rate-dependent depression of the H-reflex. In the cocoa group, the Toronto score decreased by 2.63 points and the BEST score decreased by 1.45 points. In the placebo group, these reductions were 1.84 and 2.21 points, respectively. Neither difference was statistically significant between groups (p > 0.05). Quality-of-Life questionnaire score decreased by 9.2 points in the cocoa group, but without significant difference to the placebo group (p = 0.501). Fasting glucose and HbA1c levels decreased in the placebo group by 38 mg/dL (0.28%) but were not significantly different from the cocoa group (p > 0.05). No other intra- or inter-group differences were significant (p > 0.05). Cocoa supplementation did not show significant improvements over the placebo in the measured outcomes. Both groups showed persistent abnormalities in spinal somatosensory processing, with an RDD of the H-reflex ≥ 0.5. Full article

Autonomic dysfunction of the stomach typically manifests as delayed gastric emptying or gastroparesis and is seen in individuals with both type 1 and 2 diabetes. However, impaired gastric motility is only modestly associated with the presence of upper gastrointestinal symptoms, and the diagnosis of gastroparesis essentially requires a formal measurement of gastric emptying, ideally employing a sensitive and precise technique such as scintigraphy. There is a bidirectional relationship between gastric emptying and glycemia: insulin-induced hypoglycemia accelerates, while acute elevations in blood glucose may delay gastric emptying. On the other hand, relatively more rapid emptying is associated with a higher initial rise in postprandial glucose. The management of gastroparesis requires an individualized approach, integrating dietary modifications, nutritional supplementation, pharmacological therapies, and, in severe cases, advanced interventions including gastrojejunostomy and gastric electrical stimulation. This review provides an overview of the pathophysiology and diagnosis of autonomic neuropathy of the diabetic stomach and discusses current clinical management strategies. Full article

Aim: To compare diabetic polyneuropathy (DPN) and cardiac autonomic neuropathy (CAN) between T1DM and T2DM patients. Methods: This study enrolled 66 T1DM and 79 T2DM patients. DPN was evaluated using three different methods: clinical examination, using neuropathy symptom score (NSS) and neuropathy disability score (NDS), current perception threshold (CPT) using Neurometer, and nerve conduction studies (NCSs). CAN was assessed by cardiovascular autonomic reflex tests (CARTs). Results: The prevalence of DPN did not differ between T1DM and T2DM (p > 0.05 for all), however, the proportion of DPN depended on the method used and was highest with CPT (53.0% vs. 46.8%), followed by NCSs (44.1% vs. 41.2%) and clinical examination (25.8% vs. 31.6%). T2DM vs. T1DM patients were more often diagnosed with painful DPN (51.9% vs. 27.3%, p = 0.004), reduced perception of vibration (72.2% vs. 48.5%, p = 0.006), and autonomic neuropathy (59.5% vs. 32.3%, p = 0.001), while NCSs revealed more prevalent motor nerve dysfunction in T1DM compared to T2DM (41.2% vs. 19.6%). Multivariate regression analysis showed increased DPN risk with age and CAN risk with worsening of eGFR in T1DM. No significant associations remained after multivariate adjustment for T2DM. Conclusions: The prevalence of DPN is highly varied and depends on the diagnostic method used. T2DM patients more often had symptoms and signs of diabetic neuropathy. However, stronger associations with risk factors were observed in T1DM. Full article

Background/Objectives: Obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) are two highly prevalent and interconnected conditions with significant implications for morbidity and mortality. Emerging evidence suggests a bidirectional relationship between the two disorders, mediated by shared pathophysiological mechanisms such as intermittent hypoxia, systemic inflammation, and autonomic dysfunction. Methods: A structured narrative review of the literature was conducted using a comprehensive PubMed search of clinical and observational studies published between 2020 and 2024. Studies evaluating the association between OSA and diabetes, including its effects on glycemic control, diabetic complications, and treatment outcomes, were included. Results: Thirty-three studies met our inclusion criteria. OSA is independently associated with impaired glucose metabolism, increased insulin resistance, and a higher risk of diabetic complications, including nephropathy, retinopathy, and neuropathy. Continuous positive airway pressure (CPAP) therapy has shown variable effects on metabolic outcomes, largely dependent on adherence. Traditional OSA severity metrics, such as the apnea–hypopnea index (AHI), did not consistently predict metabolic burden. Factors such as sleep quality, nocturnal hypoxemia, and comorbid insomnia have emerged as the most relevant predictors. Sex-specific differences and the roles of pharmacological and behavioral interventions were also noted. Conclusions: OSA is a modifiable and under-recognized risk factor for poor glycemic control and diabetes complications. Routine screening and individualized treatment strategies are warranted, particularly for patients with T2DM and suboptimal metabolic control. Future research should focus on defining the phenotypes at the greatest risk and developing integrated treatment pathways. Full article

Aim: The aim of this study was to evaluate the specificity, sensitivity and accuracy of the Indicator Plaster Neuropad in detecting established Diabetic Autonomic Neuropathy (DAN). Methods: We studied 180 patients with Diabetes Mellitus (DM, mean age 49.5 ± 16 years, 82 with DM type 1). All patients underwent the following Cardiovascular Reflex Tests (CARTs): R-R variation during deep breathing (Mean Circular Resultant (MCR) and standard deviation (SD)), Valsalva maneuver, R-R variability after a rapid change from lying to standing position and postural hypotension. The presence of DAN was established if ≥2 CARTs were abnormal. According to the result the patients were divided into two groups, one with DAN and one without DAN. Assessment with Neuropad was performed also in all patients. Results: Abnormal perspiration with Neuropad (uncompleted or no change in color) was detected in 94 patients. Established DAN was detected in 85 patients. The sensitivity, specificity and accuracy of Neuropad for the diagnosis of established DAN were 87.1%, 78.9% and 82.8%, respectively and area under the curve was 0.846 and 95% CI (0.787, 0.905). Conclusions: Neuropad has high sensitivity, specificity, and accuracy in detecting established DAN, as defined by ≥2 abnormal CARTs. Full article

Background: Cardiac autonomic neuropathy (CAN) is a common yet frequently underdiagnosed complication of diabetes. While our previous study demonstrated the utility of multiscale cross-approximate entropy (MS-CXApEn) in detecting early CAN, the present study further investigates the use of frequency-domain coherence analysis between systolic blood pressure (SBP) and R-R intervals (RRI) and evaluates the effects of insulin treatment on autonomic function in diabetic rats. Methods: At the onset of diabetes induced by streptozotocin (STZ), rats were assessed for cardiovascular autonomic function both before and after insulin treatment. Spectral and coherence analyses were performed to evaluate baroreflex function and autonomic regulation. Parameters assessed included low-frequency power (LFP) and high-frequency power (HFP) of heart rate variability, coherence between SBP and RRI at low and high-frequency bands (LF_Coh and HF_Coh), spontaneous and phenylephrine-induced baroreflex sensitivity (BRS_spn and BRS_phe), HRV components derived from fast Fourier transform, and MS-CXApEn at multiple scales. Results: Compared to normal controls (LF_Coh: 0.14 ± 0.07, HF_Coh: 0.19 ± 0.06), early diabetic rats exhibited a significant reduction in both LF_Coh (0.08 ± 0.04, p < 0.05) and HF_Coh (0.16 ± 0.10, p > 0.05), indicating impaired autonomic modulation. Insulin treatment led to a recovery of LF_Coh (0.11 ± 0.04) and HF_Coh (0.24 ± 0.12), though differences remained statistically insignificant (p > 0.05 vs. normal). Additionally, low-frequency LFP increased at the onset of diabetes and decreased after insulin therapy in most rats significantly, while MS-CXApEn at all scale levels increased in the early diabetic rats, and MS-CXApEn_large declined following hyperglycemia correction. The BRS_spn and BRS_phe showed no consistent trend. Conclusions: Coherence analysis provides valuable insights into autonomic dysfunction in early diabetes. The significant reduction in LF_Coh in early diabetes supports its role as a potential marker for CAN. Although insulin treatment partially improved coherence, the lack of full recovery suggests persistent autonomic impairment despite glycemic correction. These findings underscore the importance of early detection and long-term management strategies for diabetic CAN. Full article

Background: Diabetic neuropathy, particularly in its autonomic form, is often underdiagnosed despite its clinical significance. Electrochemical skin conductance (ESC), measured by SUDOSCAN, offers a non-invasive way to assess the autonomic dysfunction. Methods: A total of 288 diabetic patients were assessed using SUDOSCAN to measure ESC in the hands and feet. Clinical and laboratory parameters, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, lipid profile, and cardiovascular risk, were analyzed for correlations with ESC. Neuropathy status was evaluated, and ROC analysis was performed to assess diagnostic accuracy. Results: Sudomotor dysfunction was prevalent, particularly in patients with a diabetes duration exceeding 20 years (p < 0.05). Men showed significantly higher right foot ESC than women (76.5 ± 13.1 vs. 74.0 ± 13.5 µS, p = 0.041). A strong inverse correlation was found between cardiovascular risk score and right foot ESC (r = −0.455, p < 0.001). Left foot ESC also correlated inversely with cardiovascular risk (r = −0.401, p < 0.001) and HbA1c (r = −0.150, p = 0.049), while a weak positive correlation was seen with BMI (r = 0.145, p = 0.043). ROC analysis showed the highest area under the curve (AUC) in right foot ESC for autonomic neuropathy (AUC = 0.750, 95% CI: 0.623–0.877, p < 0.001). Conclusions: This study is among the few to systematically correlate ESC with validated cardiovascular risk scores in a diabetic outpatient cohort, highlighting its potential as a novel early screening biomarker for autonomic and cardiovascular complications. Full article

Colonoscopy is an essential diagnostic and therapeutic tool in gastroenterology, significantly impacting colorectal cancer (CRC) detection and management. Effective bowel preparation is critical for optimal visualization, directly influencing colonoscopy accuracy and patient outcomes. However, diabetic patients frequently encounter challenges achieving adequate bowel preparation, primarily due to gastroparesis, autonomic neuropathy, altered colonic motility, fluid–electrolyte imbalances, and complexities related to antihyperglycemic medication adjustments. This review aims to evaluate the current literature on bowel preparation efficacy in diabetic patients undergoing colonoscopy, assess existing guidelines from leading gastroenterological societies, and highlight the necessity for detailed, diabetes-specific recommendations. We conducted a comprehensive PubMed search identifying 20 pertinent studies, including randomized controlled trials, meta-analyses, multicenter studies, cohort studies, and reviews. The findings consistently indicate diabetes as an independent predictor of inadequate bowel preparation. Furthermore, an evaluation of guidelines from the European Society of Gastrointestinal Endoscopy (ESGE), the US Multi-Society Task Force, and the Canadian Association of Gastroenterology revealed either absent or insufficiently detailed diabetes-specific recommendations. Given the rising global prevalence of diabetes and CRC, inadequate bowel preparation significantly impacts the quality of colonoscopy, adenoma detection rates, patient safety, and healthcare costs. This review underscores the urgent need for additional research focusing on tailored bowel preparation strategies for diabetic patients. Ultimately, the implementation of standardized, evidence-based protocols designed explicitly for this high-risk group is essential to enhance diagnostic efficacy, improve patient outcomes, and reduce CRC-related morbidity and mortality. Full article

Chronic wound healing remains a major challenge in diabetes management due to prolonged inflammation, autonomic neuropathy, and bacterial infections. In particular, multidrug-resistant bacterial infections are important to the development of diabetic wounds, leading to persistent inflammation and delayed healing. To address this issue, we developed a self-adaptive nanozyme designed to modulate infectious and inflammatory microenvironments by doping Ce and Ag into mesoporous silicon nanomaterials (MSNs). The resulting CA@MSNs exhibited strong bacterial capture capabilities via electrostatic attraction. Additionally, the synergistic effects of Ce and Ag endowed CA@MSNs with peroxidase (POD)-like activity, enabling the generation of reactive oxygen species (ROS) to eradicate bacteria in infectious microenvironments. Notably, CA@MSNs also demonstrated the ability to scavenge a broad spectrum of ROS, including hydroxyl free radicals, hydrogen peroxide, and superoxide radicals, in inflammatory microenvironments. This dual functionality helped mitigate inflammation and promote endothelial cell migration. Consequently, treatment with CA@MSNs significantly reduced inflammation, enhanced fibroblast activation, and facilitated collagen deposition, ultimately accelerating the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic mice. In conclusion, this study presents a promising therapeutic strategy for chronic diabetic wounds, offering a novel approach to overcoming infection-related healing delays. Full article

Background: Diabetic autonomic neuropathy (DAN) is a severe complication of diabetes that affects the autonomic nervous system, impacting cardiovascular, gastrointestinal, genitourinary, and other systems. This study examines the levels of three potential biomarkers—DEFA1, progranulin, and NRG4—to assess their diagnostic and prognostic value in DAN patients. Methods: This observational, single-center study included 80 patients with type 2 diabetes. Clinical data and laboratory results were collected, and serum levels of DEFA1, progranulin, and NRG4 were measured using ELISA. The presence of DAN was assessed using Ewing’s tests. Statistical analyses included t-tests, Pearson’s correlations, and ROC analysis to explore associations and the predictive values of the biomarkers. Results: Progranulin levels were significantly elevated in patients with DAN compared to those without (p < 0.05), showing a positive correlation with diabetes duration (r = 0.375; p = 0.01) and a significant predictive value for DAN (AUC = 0.666; p = 0.013). DEFA1 and NRG4 levels did not differ significantly between the groups. Progranulin was also higher in patients who were treated with sulfonylureas and GLP-1 receptor agonists and in those with coronary artery disease. Conclusions: Progranulin emerges as a potential biomarker for the presence and severity of DAN, correlating with disease duration and autonomic dysfunction. While DEFA1 and NRG4 showed no significant association, the findings underscore the importance of further exploring the inflammatory pathways in DAN. Progranulin measurement could enhance early diagnosis and personalized management of autonomic neuropathy in diabetes. Full article

The present study was conducted in type 1 diabetic (T1DM) patients to evaluate the metabolic and glycemic control as well as the manifestations of neuropathy. The impact of continuous glucose monitoring (CGM) on the measured parameters was also analyzed. A total of 61 T1DM patients (age: 42.5 ± 1.8 years, DM duration: 22.8 ± 1.6 years, mean ± SE) participated in the study. In total, 24 patients had CGM sensors and 37 did not. Cardiovascular autonomic neuropathy was assessed using cardiovascular reflex tests. Peripheral sensory function was evaluated by a Neurometer and calibrated tuning fork on the upper and lower limbs. Metabolic status was characterized by the determination of triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and glycated haemoglobin (HbA_1c). A positive correlation was found between HbA_1c and triglyceride levels (r = 0.28, p < 0.05). CGM users and non-users differed in triglyceride (0.9 ± 0.1 vs. 1.24 ± 0.12 mmol/L, p < 0.05), HDL cholesterol (1.7 ± 0.1 vs. 1.4 ± 0.1 p < 0.05 mmol/L), and HbA_1c (7.5 ± 0.2 vs. 8.3 ± 0.3%, p < 0.05) levels as well. Significant differences were found for the Valsalva ratio, Neurometer, and calibrated tuning fork results between CGM users and non-users. This study found a significant correlation between HbA_1c and triglyceride levels in T1DM. CGM use resulted in improved metabolic parameters and less autonomic and sensory nerve damage. As a novel finding, CGM is presumed to prevent both micro-, and macrovascular complications and, by this way, potentially reducing mortality rates. Full article