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Type 1 diabetes (T1D) severely impairs metabolic control and can lead to erectile dysfunction (ED) through hyperglycemia-induced vascular damage, autonomic neuropathy, and psychological distress. This review examines the role of continuous glucose monitoring (CGM) in ameliorating ED by addressing glucose variability and inflammation. A comprehensive analysis of studies and clinical trials was conducted to evaluate the impact of CGM on metabolic control, inflammatory responses, and vascular health in patients with T1D. Evidence suggests that CGM systems significantly stabilize blood glucose levels and reduce hyper- and hypoglycemic episodes that contribute to endothelial dysfunction and ED. CGM's real-time feedback helps patients optimize metabolic control, improve vascular health, and reduce inflammation. CGM has the potential to redefine ED management in patients with T1D by improving glycemic control and reducing the physiological stressors that cause ED, potentially improving quality of life and sexual health. Further research is warranted to explore the specific benefits of CGM for ED management. [ABSTRACT FROM AUTHOR]

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

Background: Symptoms of autonomic neuropathy (AN) are common in patients with diabetes and advanced renal disease. As yet different domains of autonomic neuropathy cannot be detected by a singular laboratory or invasive test. COMPASS 31, a new self-assessment test, has shown reliable results not only in cardiac autonomic neuropathy but also in different sub-domains when judging manifestation of AN by scores. Methods: One hundred eighty-three patients with or without diabetes were enrolled, one hundred nineteen of them were treated with permanent dialysis therapy (HD), sixty-four patients served as controls (eGFR > 60 ml/min.) Using COMPASS 31 different symptoms of AN were assessed (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes) and transferred into AN-scores. Results: AN was more pronounced in dialysis patients compared with controls (AN-score 27,5 vs. 10,0; p < 0,01). These differences were present also in every sub-domain of AN (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes; p < 0,05 for all sub-domains). In diabetic patients there was a strong correlation between symptoms of AN and diabetes duration (correlation coefficient r = 0,45, p < 0,001). Current glycemic control (HbA1c), body mass index (BMI), sex, and height had no influence on AN when comparing dialysis patients and controls. C-reactive protein (CRP) showed a positive linear correlation with AN-scores (correlation coefficient r = 0,21; p < 0,05). Conclusion: Symptoms of AN are more pronounced in dialysis patients not only in total but also in all different domains of neuropathic changes. Longlasting diabetic disease promotes development of AN, as duration of diabetes was positively correlated with AN. Future longitudinal studies might help to identify the high cardiovascular and mortality risk in dialysis patients by the easy-to-use COMPASS 31 without need of invasive and time-spending methods for diagnosing AN. [ABSTRACT FROM AUTHOR]

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

Abstract Background Symptoms of autonomic neuropathy (AN) are common in patients with diabetes and advanced renal disease. As yet different domains of autonomic neuropathy cannot be detected by a singular laboratory or invasive test. COMPASS 31, a new self-assessment test, has shown reliable results not only in cardiac autonomic neuropathy but also in different sub-domains when judging manifestation of AN by scores. Methods One hundred eighty-three patients with or without diabetes were enrolled, one hundred nineteen of them were treated with permanent dialysis therapy (HD), sixty-four patients served as controls (eGFR > 60 ml/min.) Using COMPASS 31 different symptoms of AN were assessed (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes) and transferred into AN-scores. Results AN was more pronounced in dialysis patients compared with controls (AN-score 27,5 vs. 10,0; p

Abstract Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.

Aim: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). Materials and Methods: We used motif and discord extraction techniques, alongside long short‐term memory networks, to analyse 12‐lead, 10‐s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10‐fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver‐operating characteristic curve (AUC). Results: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91–0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54–0.81). Conclusion: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large‐scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated. [ABSTRACT FROM AUTHOR]

Due to the majority of currently available genome data deriving from individuals of European ancestry, the clinical interpretation of genomic variants in individuals from diverse ethnic backgrounds remains a major diagnostic challenge. Here, we investigated the genetic cause of a complex neurodevelopmental phenotype in two Palestinian siblings. Whole exome sequencing identified a homozygous missense TECPR2 variant (Chr14(GRCh38):g.102425085G>A; NM_014844.5:c.745G>A, p.(Gly249Arg)) absent in gnomAD, segregating appropriately with the inheritance pattern in the family. Variant assessment with in silico pathogenicity prediction and protein modeling tools alongside population database frequencies led to classification as a variant of uncertain significance. As pathogenic TECPR2 variants are associated with hereditary sensory and autonomic neuropathy with intellectual disability, we reviewed previously published candidate TECPR2 missense variants to clarify clinical outcomes and variant classification using current approved guidelines, classifying a number of published variants as of uncertain significance. This work highlights genomic healthcare inequalities and the challenges in interpreting rare genetic variants in populations underrepresented in genomic databases. It also improves understanding of the clinical and genetic spectrum of TECPR2‐related neuropathy and contributes to addressing genomic data disparity and inequalities of the genomic architecture in Palestinian populations. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. Methods: This study included adults (aged 20–86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. Results: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: −0.26 ± 0.64 vs −0.17 ± 0.62, p=0.44; GSRS: −0.35 ± 0.62 vs −0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: −0.47 ± 0.78 vs −0.33 ± 0.75, p=0.34; GSRS: −0.46 ± 0.90 vs −0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs −19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. Conclusions/interpretation: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. Trial registration: ClinicalTrials.gov NCT04143269 Funding: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045) [ABSTRACT FROM AUTHOR]

Background Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. Combination medicines and pure methylcobalamin seems to improve symptoms rather than electrophysiologic outcomes in individuals with diabetic peripheral neuropathy. The aim of present study was to assess the effect of Vitamin B supplementation for diabetic peripheral neuropathy. Methods The present cross-sectional study was conducted at department of general medicine among 100 patients with diabetic peripheral neuropathy who visited during the study period of one year. Patients were divided into two groups (group B and group P). The entire neuropathy and laboratory test were done. With IBM SPSS v25.0, statistical analyses were carried out. Results There were no significant differences between the group B and group P regarding demographics, anthropometric and laboratory measurements. Vitamin B12 levels significantly increased in the group B from 237.8±70.3 pmol/L at baseline to 775.8±234.2 pmol/L at follow-up. In the group B, there was a significant improvement in the vibration perception threshold (VPT), MNSIQ, pain score, quality of life (QoL), sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and electrochemical skin conductance in feet (ESCF) during the follow-up (p =0.001, p = 0.003, p = 0.0001, p = 0.0001, and p = 0.013, respectively). Conclusion Patients with DN who received an oral methylcobalamin treatment for a whole year had improvements in their QoL, pain score, sudomotor function, plasma B12 levels, and all neurorophysiological markers; however, CARTS and MNSIE did not show any improvement. [ABSTRACT FROM AUTHOR]

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (TTRv) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis. [ABSTRACT FROM AUTHOR]

Background. Orthostatic hypotension (OH) stands as one of the initial indications of cardiac autonomic dysfunction in diabetic individuals. Our objective is to assess the prevalence of OH across different degrees of diabetes. Materials and methods. This study is a cross-sectional investigation conducted at a tertiary care center. After obtaining ethical committee clearance and informed consent, 150 individuals aged above 50 years were recruited for this study. 50 of them had normal HbA1c levels, 50 with HbA1c levels between 7-8 and another 50 individuals with more than 8 HbA1c values. Results. The duration of diabetes exhibited a strong correlation with HbA1c levels, which was statistically significant (p=0.000). The systolic BP difference in normal, HbA1c 7-8 and HbA1c levels more than 8 were 6.34±1.95, 15.70±8.37 and 17.04±7.74 respectively. The diastolic BP difference in normal, HbA1c 7-8 and HbA1c levels more than 8 were 4.00±1.42, 7.72±5.26 and 12.22±7.77. These results were found to be statistically significant (p=0.000). Conclusion. OH serves as an ominous sign in diabetic patients, indicating a poor prognosis. Individuals with OH are at a heightened risk of falls, which in turn, is associated with increased morbidity and mortality. Therefore, it is crucial to prioritize the early detection of autonomic neuropathy, particularly in diabetic patients. [ABSTRACT FROM AUTHOR]

Introduction: Autonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy. Methods: FINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (=12 points, n = 44; control <12 points, n = 28). HbA1c levels >5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model. Results: Mean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m² vs. 25.9 ± 8.9 kg/m²). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08-32.68; p < 0.041). Discussion: An increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown. [ABSTRACT FROM AUTHOR]

Background and Objectives: Diabetes Mellitus (DM) is a significant health concern in India, characterized as a modern-day epidemic, with the potential to affect multiple organs and lead to various complications. Cardiac autonomic neuropathy (CAN) represents one of the serious yet often overlooked complications of diabetes. This study aims to ascertain the prevalence of CAN in diabetic patients and investigate its correlation with the duration of DM and glycemic control. Materials and Methods: 134 diabetic patients were included based on predetermined criteria. Demographic information, medical history, and clinical examinations were recorded. CAN assessment involved three tests for parasympathetic and two tests for sympathetic function, with patients categorized as normal, early CAN, definite CAN, or severe CAN according to Ewing's criteria. Results: The prevalence of CAN among the study population was 60%. Individuals with CAN exhibited significantly longer durations of diabetes and higher HbA1c levels compared to those with normal cardiac autonomic function. CAN showed a significant association with DM duration and glycemic control, but not with age. CAN patients presented with background retinopathy, various retinopathies, maculopathy and clinical symptoms such as diabetic foot, cataracts, muscle wasting, and tingling. Conclusion: CAN emerges as a prevalent and often asymptomatic consequence of diabetes. Hence, routine screening for CAN is recommended for all diabetic patients to facilitate early detection and intervention. [ABSTRACT FROM AUTHOR]

Not available

Type 1 diabetes (T1D) severely impairs metabolic control and can lead to erectile dysfunction (ED) through hyperglycemia-induced vascular damage, autonomic neuropathy, and psychological distress. This review examines the role of continuous glucose monitoring (CGM) in ameliorating ED by addressing glucose variability and inflammation. A comprehensive analysis of studies and clinical trials was conducted to evaluate the impact of CGM on metabolic control, inflammatory responses, and vascular health in patients with T1D. Evidence suggests that CGM systems significantly stabilize blood glucose levels and reduce hyper- and hypoglycemic episodes that contribute to endothelial dysfunction and ED. CGM’s real-time feedback helps patients optimize metabolic control, improve vascular health, and reduce inflammation. CGM has the potential to redefine ED management in patients with T1D by improving glycemic control and reducing the physiological stressors that cause ED, potentially improving quality of life and sexual health. Further research is warranted to explore the specific benefits of CGM for ED management.

Type 2 diabetes mellitus (T2DM) is characterized by several complications, such as retinopathy, renal failure, cardiovascular disease, and diabetic neuropathy. Among these, neuropathy is the most severe complication, due to the challenging nature of its early detection. The linear Hearth Rate Variability (HRV) analysis is the most common diagnosis technique for diabetic neuropathy, and it is characterized by the determination of the sympathetic–parasympathetic balance on the peripheral nerves through a linear analysis of the tachogram obtained using photoplethysmography. We aimed to perform a multifractal analysis to identify autonomic neuropathy, which was not yet manifest and not detectable with the linear HRV analysis. We enrolled 10 healthy controls, 10 T2DM-diagnosed patients with not-full-blown neuropathy, and 10 T2DM diagnosed patients with full-blown neuropathy. The tachograms for the HRV analysis were obtained using finger photoplethysmography and a linear and/or multifractal analysis was performed. Our preliminary results showed that the linear analysis could effectively differentiate between healthy patients and T2DM patients with full-blown neuropathy; nevertheless, no differences were revealed comparing the full-blown to not-full-blown neuropathic diabetic patients. Conversely, the multifractal HRV analysis was effective for discriminating between full-blown and not-full-blown neuropathic T2DM patients. The multifractal analysis can represent a powerful strategy to determine neuropathic onset, even without clinical diagnostic evidence. [ABSTRACT FROM AUTHOR]

Introduction: Activation of sympathetic nervous system, increase of catabolic hormone release and pituitary gland suppression are responses to surgical stress. Neural blockade via epidural or spinal anesthesia, intravenous administration of high-dose of strong opioid analgesics, and infusion of anabolic hormones such as insulin are three main methods for balancing stress responses to surgery. However, there are conflicting reports about the extent of autonomic disturbances occurring after inducing spinal anesthesia in diabetic patients due to underlying autonomic neuropathy. Methodology: An observational cohort study was conducted in an operative room of a tertiary health care center involving 25 diabetic patients and 25 non-diabetic patients to evaluate the tolerance to stress. The diabetic patients undergone an exercise tolerance test to evaluate for postural hypotension which would indicate presence of autonomic neuropathy. Stress parameters such as heart rate, mean blood pressure, blood glucose level, and temperature were measured at regular intervals pre, peri- and post-operatively. Results: Intraoperative heart rate, mean blood pressure, and blood glucose level were high in diabetic patients with autonomic neuropathy (p≤0.05). Temperature was higher in diabetic patients with autonomic neuropathy initially (p≤0.05) and had a higher fall peri-and post-operatively (T=15 minutes, T=20 minutes, and T=after surgery). A significant differences in the parameters of stress response were observed in diabetic patients with autonomic neuropathy. Conclusion: By understanding the correlation between stress-response in diabetic patients with autonomic neuropathy peri-operatively will help the anesthetist to provide customized services to every patient. [ABSTRACT FROM AUTHOR]

The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2–5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p ≤ 0.025 for each). Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV. [ABSTRACT FROM AUTHOR]

IntroductionAutonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy.MethodsFINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (≥12 points, n = 44; control 5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model.ResultsMean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m2 vs. 25.9 ± 8.9 kg/m2). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08–32.68; p < 0.041).DiscussionAn increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown.

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis. [ABSTRACT FROM AUTHOR]

Background: India is sometimes called the "diabetic capital of the world" due to the country's alarmingly rising rate of diabetes mellitus. Worldwide, Type 2 Diabetes has become a serious health issue. Material and Methods: From the pool of Type 2 Diabetics receiving care at NRIIMS's General Medicine Department in Visakhapatnam, 100 patients met the study's inclusion and exclusion criteria. From October 2021 to December 2022, a full year of data was collected for this investigation. Results: This study's findings add to the growing body of evidence showing that cardiac autonomic dysfunction is widespread among diabetic patients. Multiple investigations, some of which were carried out in India, have found findings that are consistent with one another. Using validated but basic measures of cardiovascular autonomic function, this study showed severe anomalies in autonomic function. Conclusion: The study found the following results, our hospital's research group found a high prevalence of cardiovascular autonomic neuropathy among type 2 diabetes. As diabetes progresses, so does the risk of developing CAN. [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) is often associated with endocrine complications. The article describes a clinical case of the patient with type 2 diabetes mellitus and COVID-19 after which, for the first time, there was a need for basal-bolus insulin therapy, and secondly, a significant arterial hypotension occurred. The mechanism of damage to β-cells of the pancreas in the patient is debatable. After analyzing the features of diabetes course, we found an acute onset of the disease at the age of 44 years with pronounced hyperglycemia and ketosis, which required insulin therapy. Then for a long time there was no need in insulin therapy, and the patient took metformin, having overweight, no antibodies to β-cell antigens. It is also impossible to exclude the effect of SARS-CoV-2 on the secretory function of β-cells of the pancreas. Accordingly, clinical cases are interesting, as their analysis helps to understand not only the mecha­nism of development and progression of this infection, but also the diagnosis and treatment of its complications. We have described a rare clinical case of the hyporeninemic hypoaldosteronism in the patient with type 2 diabetes mellitus after COVID-19 infection. A feature of the hyporeninemic hypoaldosteronism course was the absence of electrolyte disorders in the patient, with severe arterial hypotension, suppression of renin and aldosterone. We believe that the hyporeninemic hypoaldosteronism has been associated with the progression of chronic diabetes complications, mainly autonomic neuropathy against the background of COVID-19. To improve the identified disorders, replacement therapy with mineralocorticoids was prescribed. The blood pressure, symptoms of fluid retention and electrolyte levels were monitored when selecting the dose of fludrocortisone. The patient has been under observation for 14 months, the need for fludrocortisone replacement therapy persists to this day. Practicing doctors need to pay attention to the diagnosis of autonomic disorders, which reduce the patients’ quality of life and are an independent risk factor for cardiovascular mortality.

Abstract Background Diabetic autonomic neuropathy (DAN) is a frequent complication in people with diabetes whose screening is often neglected. This study aimed to evaluate DAN through practical tools in people with diabetes in a referral center for diabetes treatment. Methods DAN symptoms and severity were assessed using the Survey of Autonomic Symptoms (SAS) via digital application (app) in patients attended from June 1, 2021, to November 12, 2021. SAS scoring for DAN was performed using established validated cutoffs. The adhesive with cobalt salt color indicator (Neuropad™) was used as a measure of sudomotor dysfunction. Demographical and clinical data were also collected. Results Data from 109 participants, 66.9% T2DM, 73.4% female, with a median age of 54.00 (± 20.00) years, were analyzed. Symptomatic DAN was present in 69.7% of participants and was associated with older age (p = 0.002), higher HbA1c (p = 0.043), higher abdominal circumference (p = 0.019), higher BMI (p = 0.013), more likely to have metabolic syndrome (MS) with a 10-fold increased risk, and more frequent association with diabetic peripheral neuropathy (p = 0.005). Sudomotor dysfunction was found in 65 participants with positive Neuropad™ detected in 63.1% of them. Conclusion The use of SAS through an app proved to be a practical and easy-to-use instrument to document symptoms of DAN in busy clinical practice. The high frequency of symptoms draws attention to the importance of screening this underdiagnosed diabetes complication. The risk factors and comorbidities associated with symptomatic DAN highlight the patients’ phenotypes linked to MS that should be targeted for DAN evaluations in larger samples in the community.

Modern medicine exhibits an upward trend towards non-invasive methods for early detection of disease and long-term monitoring of patients’ health. Diabetes mellitus and its complications are a promising area for implementation of new medical diagnostic devices. One of the most serious complications of diabetes is diabetic foot ulcer. The main causes responsible for diabetic foot ulcer are ischemia caused by peripheral artery disease and diabetic neuropathy caused by polyol pathway-induced oxidative stress. Autonomic neuropathy impairs function of sweat glands, which can be measured by electrodermal activity. On the other hand, autonomic neuropathy leads to changes in heart rate variability, which is used to assess autonomic regulation of the sinoatrial node. Both methods are enough sensitive to detect pathological changes caused by autonomic neuropathy and are promising screening methods for early diagnosis of diabetic neuropathy, which could prevent the onset of diabetic ulcer.

Dorsal root ganglia (DRG), trigeminal ganglia (TG), other sensory ganglia, and autonomic ganglia may be injured by some test article classes, including anti-neoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, nerve growth factor inhibitors, and aminoglycoside antibiotics. This article reviews ganglion anatomy, cytology, and pathology (emphasizing sensory ganglia) among common nonclinical species used in assessing product safety for such test articles (TAs). Principal histopathologic findings associated with sensory ganglion injury include neuron degeneration, necrosis, and/or loss; increased satellite glial cell and/or Schwann cell numbers; and leukocyte infiltration and/or inflammation. Secondary nerve fiber degeneration and/or glial reactions may occur in nerves, dorsal spinal nerve roots, spinal cord (dorsal and occasionally lateral funiculi), and sometimes the brainstem. Ganglion findings related to TA administration may result from TA exposure and/or trauma related to direct TA delivery into the central nervous system or ganglia. In some cases, TA-related effects may need to be differentiated from a spectrum of artifactual and/or spontaneous background changes. [ABSTRACT FROM AUTHOR]

Purpose of eview: The aim of this review is to discuss the presentation, diagnosis, and management of polyneuropathy (PN) in selected infections. Overall, most infection related PNs are an indirect consequence of immune activation rather than a direct result of peripheral nerve infection, Schwann cell infection, or toxin production, though note this review will describe infections that cause PN through all these mechanisms. Rather than dividing them by each infectious agent separately, we have grouped the infectious neuropathies according to their presenting phenotype, to serve as a guide to clinicians. Finally, toxic neuropathies related to antimicrobials are briefly summarized. Recent findings: While PN from many infections is decreasing, increasing evidence links infections to variants of GBS. Incidence of neuropathies secondary to use of HIV therapy has decreased over the last few years. Summary: In this manuscript, a general overview of the more common infectious causes of PN will be discussed, dividing them across clinical phenotypes: large- and small-fiber polyneuropathy, Guillain-Barré syndrome (GBS), mononeuritis multiplex, and autonomic neuropathy. Rare but important infectious causes are also discussed. [ABSTRACT FROM AUTHOR]

Sjogren's Syndrome is an autoimmune disorder characterized by the loss of salivary and lacrimal glands, resulting in dry mouth and eyes. Erectile dysfunction (ED) is a prevalent complaint among people with Sjogren's Disease, however the underlying mpoiechanism is not yet known. The purpose of this article is to examine the mechanism through which Sjogren's Disease causes ED and to identify potential therapies. Using MEDLINE, EMBASE, and the Cochrane Library databases, a systematic review was done. Papers investigating the link between Sjogren's Syndrome and ED published between 1990 and 2021 were included in the study. The review paper discusses a number of potential mechanisms for the association between Sjogren's Disease and ED. They include low levels of testosterone, endothelial dysfunction, autonomic neuropathy, and psychosocial issues. The article also discusses potential treatments for ED caused by Sjogren's Disease, including inhibitors of phosphodiesterase type 5, testosterone replacement therapy, and psychological counseling. The research implies a connection between Sjogren's Disease and ED, although the underlying mechanisms remain unknown. It is necessary to conduct additional studies to better comprehend the relationship and develop targeted remedies. [ABSTRACT FROM AUTHOR]

Background: Diabetes and hypertension are known to co-exist frequently as adverse cardiovascular risk factors. Both can produce cardiac autonomic neuropathy that can be measured by ECG RR interval-based heart rate variability (HRV). We compared 5 minutes HRV in four groups based on diabetes and hypertension. Methodology: A cross sectional study was done on 203 participants divided into four groups-diabetics, hypertensives, diabetic-hypertensives and normotensive-nondiabetics. They were evaluated for current disease control and five minutes HRV was done in supine condition following standard protocols by Variowin HR Software. HRV parameters of time domain, frequency domain and Poincare plot were compared between groups and associated with gender, glycaemic control and blood pressure control. Statistical significance was set at p<0.05. Results: Three diseased groups had mean age in mid-fifties, mean duration of disease > 6 years, comparable BMI, poor glycaemic and blood pressure control. As compared to normal groups, three diseased groups exhibit reduced HRV with respect to all three domains of HRV with varying statistical significance. Among diseased groups, HRV was associated with blood pressure control better than glycaemic control but not with gender. LF/HF ratio was the most consistent HRV parameter showing statistical significance in tests. Conclusion: HRV is reduced in both diabetics more than hypertensives; related to blood pressure control more than glycaemic control. It points altered cardiac autonomic balance, and possibility of cardiovascular risk and early detection of it with timely intervention. It also calls for investigation of same for reinforcement of our observations and further exploration. [ABSTRACT FROM AUTHOR]

Background: Diabetic autonomic neuropathy (DAN) is a frequent complication in people with diabetes whose screening is often neglected. This study aimed to evaluate DAN through practical tools in people with diabetes in a referral center for diabetes treatment. Methods: DAN symptoms and severity were assessed using the Survey of Autonomic Symptoms (SAS) via digital application (app) in patients attended from June 1, 2021, to November 12, 2021. SAS scoring for DAN was performed using established validated cutoffs. The adhesive with cobalt salt color indicator (Neuropad™) was used as a measure of sudomotor dysfunction. Demographical and clinical data were also collected. Results: Data from 109 participants, 66.9% T2DM, 73.4% female, with a median age of 54.00 (± 20.00) years, were analyzed. Symptomatic DAN was present in 69.7% of participants and was associated with older age (p = 0.002), higher HbA1c (p = 0.043), higher abdominal circumference (p = 0.019), higher BMI (p = 0.013), more likely to have metabolic syndrome (MS) with a 10-fold increased risk, and more frequent association with diabetic peripheral neuropathy (p = 0.005). Sudomotor dysfunction was found in 65 participants with positive Neuropad™ detected in 63.1% of them. Conclusion: The use of SAS through an app proved to be a practical and easy-to-use instrument to document symptoms of DAN in busy clinical practice. The high frequency of symptoms draws attention to the importance of screening this underdiagnosed diabetes complication. The risk factors and comorbidities associated with symptomatic DAN highlight the patients’ phenotypes linked to MS that should be targeted for DAN evaluations in larger samples in the community. [ABSTRACT FROM AUTHOR]

Aim: In this study, it was aimed to examine the effects of metabolic syndrome, which affects many organs, on the autonomic nervous system and to observe the changes after treatment. Materials and Methods: Heart rate variability values of 101 metabolic syndrome patients who were treated at the Kocaeli University Cardiology Outpatient Clinic included in the study. All patients were offered lifestyle change suggestions in addition to their medical treatments. At the end of three months, the heart rate variability parameters of the patients were re-evaluated. Results: Heart rate variability values were found to be significantly lower in metabolic syndrome patients compared to the control group. It was observed that the heart rate variability values improved significantly in half of the patients who applied the given treatment with lifestyle changes. A decrease in heart rate change parameters was found in the group that did not implement lifestyle changes compared to the beginning of the study. Conclusion: Autonomic nervous system functions evaluated by heart rate variability decreased in patients with metabolic syndrome, and the treatment and lifestyle changes had a positive effect on these parameters. [ABSTRACT FROM AUTHOR]

Background: To assess the prevalence of objective signs of gastrointestinal (GI) autonomic neuropathy (AN) in adolescents with type 1 diabetes (T1D). In addition, to investigate associations between objective GI findings and self-reported symptoms or other findings of AN. Methods: Fifty adolescents with T1D and 20 healthy adolescents were examined with a wireless motility capsule to assess the total and regional GI transit times and motility index. GI symptoms were evaluated with the GI Symptom Rating Scale questionnaire. AN was evaluated with cardiovascular and quantitative sudomotor axon reflex tests. Results: There was no difference in GI transit times in adolescents with T1D and healthy controls. Adolescents with T1D had a higher colonic motility index and peak pressure than the controls, and GI symptoms were associated with low gastric and colonic motility index (all p < 0.05). Abnormal gastric motility was associated with the duration of T1D, while a low colonic motility index was inversely associated with "time in target range" for blood glucose (all p < 0.01). No associations were found between signs of GI neuropathy and other measures of AN. Conclusions: Objective signs of GI neuropathy are common in adolescents with T1D and it seems to require early interventions in patients at high risk of developing GI neuropathy. [ABSTRACT FROM AUTHOR]

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima–media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a rapidly rising metabolic disorder with important systemic complications. Global figures have demonstrated the prevalence of diabetes mellitus has almost quadrupled from 108 million in 1980 to 422 million in 2014, with a current prevalence of over 525 million. Of the male sexual dysfunction resulting from diabetes mellitus, significant focus is afforded to erectile dysfunction. Nevertheless, ejaculatory dysfunction constitutes important sexual sequelae in diabetic men, with up to 35%-50% of men with diabetes mellitus suffering from ejaculatory dysfunction. Despite this, aspects of its pathophysiology and treatment are less well understood than erectile dysfunction. The main disorders of ejaculation include premature ejaculation, delayed ejaculation, anejaculation and retrograde ejaculation. Although ejaculatory dysfunction in diabetes mellitus can have complex multifactorial aetiology, understanding its pathophysiological mechanisms has facilitated the development of therapies in the management of ejaculatory dysfunction. Most of our understanding of its pathophysiology is derived from diabetic animal models; however, observational studies in humans have also provided useful information in elucidating important associative factors potentially contributing to ejaculatory dysfunction in diabetic men. These have provided the potential for more tailored treatment regimens in patients depending on the ejaculatory disorder, other co-existing sequelae of diabetes mellitus, specificmetabolic factors as well as the need for fertility treatment. However, evidence for treatment of ejaculatory dysfunction, especially delayed ejaculation and retrograde ejaculation, is based on low-level evidence comprising small sample-size series and retrospective or cross-sectional studies. Whilst promising findings from large randomised controlled trials have provided strong evidence for the licensed treatment of premature ejaculation, similar robust studies are needed to accurately elucidate factors predicting ejaculatory dysfunction in diabetes mellitus, as well as for the development of pharmacotherapies for delayed ejaculation and retrograde ejaculation. Similarly, more contemporary robust data are required for fertility outcomes in these patients, including methods of sperm retrieval and assisted reproductive techniques in retrograde ejaculation. [ABSTRACT FROM AUTHOR]