Autonomic Neuropathy Research Articles

The Presence of Ganglionic Acetylcholine Receptor Antibodies in Sera from Patients with Functional Gastrointestinal Disorders: A Preliminary Study.

Functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and irritable bowel syndrome (IBS), are characterized by chronic and recurrent gastrointestinal symptoms. Clinically, FD and IBS often resemble gastrointestinal dysmotility caused by autoimmune autonomic neuropathy. We examined the seropositive frequency of autoantibodies against ganglionic nicotinic acetylcholine receptors (gnAChRs) in patients presenting with FGIDs. To elucidate the seropositivity of gnAChR antibodies and the clinical features of seropositive FD and IBS. We measured autoantibodies against the gnAChR α3 and β4subunits using luciferase immunoprecipitation systems. Serum samples from patients with any autonomic symptoms were obtained from hospitals in Japan between January 2012 and August 2018 (1787 serum samples of 1381 patients). We selected FD and IBS patients and compared the clinical characteristics and prevalence of autonomic symptoms between those with seropositive and seronegative IBS and FD. Nine IBS and two FD cases (one comorbid case with IBS) were found. We found four patients (36.4%) in whom gnAChR antibodies were positive in these eleven patients. Sicca symptoms were observed in three of four cases (75%) of seropositive FGID compared with zero of seven cases (0%) of seronegative FGID. We found patients with gnAChR antibodies in FD and IBS patients. These data will be valuable for elucidating the pathophysiology of these FGIDs and developing new treatment strategies.

Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic

BackgroundPopulation-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes. MethodsIn a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index. ResultsWe included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15–40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11−22] years).Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9–49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D. ConclusionThe prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases.

Diabetic cardiovascular autonomic neuropathy: clinical significance, diagnosis and therapy

Diabetic cardiovascular autonomic neuropathy: clinical significance, diagnosis and therapy

Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population

BackgroundType 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. MethodIn this case-control study we recruited 126 adolescents (13–22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. ResultsThe mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37–5.64; p = 0.005), LDL (2.66, 95%CI:1.19–5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57–19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. ConclusionIn this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy – A Danes cohort study

ObjectiveWe investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) – Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. Research design and methodsCross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation.Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. ResultsWe included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. ConclusionsA high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Complications during Adolescence Predict Mortality in Young Adults with Childhood Onset Type 1 Diabetes

Objective. Microvascular complications increase the risk of cardiovascular disease and premature death in adults with type 1 diabetes. We examined the association between microvascular complications during adolescence, including cardiac autonomic nerve dysfunction and subsequent mortality. Research Design and Methods. We undertook data linkage with the Australian National Death Index in a cohort of 409 adolescents (diagnosed between 1973 and 1993), 48% male, median age at final complications assessment 17.4 years (interquartile range: 16.0–18.9), followed longitudinally for median 22.3 years (21.0–23.4) from diagnosis. Generalized estimating equations (GEE) were used to examine associations between mortality and adolescent complications. Mortality risk was calculated as standardized mortality ratio (SMR). Results. At final adolescent visit, 20% had CAN abnormality, 30% abnormal pupillary response, 20% albuminuria, 40% early elevation of albumin excretion rate (AER) and 45% retinopathy. Data linkage 8–13 years later showed 14 were deceased (3% of cohort), 57% male, median age 28.3 years (24.8–32.9). Acute or chronic diabetes complications accounted for 25% of deaths. In multivariable GEE, elevated AER (OR 4.54, 1.23–16.80, p=0.030), pupillary abnormality (OR 4.27, 1.20–15.22, p=0.023), systolic blood pressure SDS (OR 2.17, 1.26–3.74, p=0.005) and CAN (OR 4.65, 1.03–21.0, p=0.045) predicted mortality. HbA1c was not significant. SMR was 2.5 (1.4–4.2) and was higher in females (SMR 3.5, 1.3–7.8) but not in males (SMR 2.1, 0.9–4.0). Conclusion. Mortality in young adults with type 1 diabetes is predicted by subclinical markers of autonomic neuropathy and elevated AER during adolescence, but not glycemia. Mortality was over twice that of the background population in females but not in males.

Artificial intelligence-enhanced electrocardiogram analysis for identifying cardiac autonomic neuropathy in patients with diabetes.

To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN). 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). 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). 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.

The Effect of Intra-abdominal Pressure on Heart Rate Variability and Hemodynamics During Laparoscopic Cholecystectomy: A Prospective Observational Study.

Introduction This study aimed to evaluate hemodynamic changes using heart rate variability (HRV) measurements in diabetic and nondiabetic patients who will undergo laparoscopic cholecystectomy and to provide our preoperative measurements to guide us for better perioperative anesthesia management. Materials and methods The study included 143 patients aged 40 years and older who would undergo elective laparoscopic surgery, did not have any comorbidities other than diabetes mellitus (DM) type II, and were in theAmerican Society of Anesthesiologists(ASA) class I-III risk group. Patients were divided into two groups: the control group (n = 77) and the DM group (n = 66). The preoperativeglycated hemoglobin (HbA1C) level was measured. Peripheral oxygen saturation (SpO2) and hemodynamic parameters such as systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and HRV parameters were measured preoperatively, perioperatively, and postoperatively. Intra-abdominal pressure (IAP) was administered at 10-12 mmHg. Results Even though SAP, DAP, MAP, and HR decreased with induction, they increased with insufflation, and an overall decrease was seen at the postoperative 24th hour for all parameters. When the groups were evaluated, no difference was observed except that the DAP was significantly lower in the DM group (p = 0.029) at insufflation and the HR was higher in the DM group at induction, and the difference was significant (p = 0.001). Preoperative HRV parameters were significantly lower in the DM group. According to the HRV parameters, although a decrease was observed after induction and insufflation, conversely, an increase was observed postoperatively. When the postoperative and preoperative values were compared, the standard deviation of the NN (R-R) intervals (SDNN), SDNN index, high frequency (HF), low frequency (LF), and LF/HF parameters were found to be significantly lower in the DM group than in the control group. Conclusion Diabetic patients are more sensitive to increased intra-abdominal pressure (IAP) in laparoscopic surgery, and the effects on cardiac autonomic functions can be determined by HRV measurements without clinically reflecting on hemodynamic data. Additionally, in diabetic patients with preoperative LF and/or HF values less than 100, we believe that careful follow-up in terms of autonomic neuropathy complications and anesthesia management should be done more meticulously in these patients.

The Incidence of Cardiac Autonomic Neuropathy in Patients with Amyotrophic Lateral Sclerosis – A Systematic Review (P5-3.006)

The Incidence of Cardiac Autonomic Neuropathy in Patients with Amyotrophic Lateral Sclerosis – A Systematic Review (P5-3.006)

Taste Dysfunction and its Relationship to HbA1C Level and Disease Duration in Type 2 Diabetes Mellitus Patients with Autonomic Neuropathy

Background and Aim: Type 2 diabetes mellitus (T2DM) effect quality of life very much and causes variouscomplications. Diabetic autonomic neuropathy (DAN) is one of the common complications in diabetes. Thuspresent study was aimed at determining taste dysfunction in a population of T2DM subjects and its correlation with HbA1c level.Material and Methods: This was an observational cross sectional study which was carried over a period of one year in the department of medicine, Tertiary care institute of India. The 100 patients of T2DM with autonomicneuropathy and 100 healthy controls were taken for the study. Autonomic neuropathy was assessed clinically.Chemical taste test using four solutions of basic tastes (sweet, sour, salty, bitter) were done.Results: There was a significant difference between the 2 groups in terms of HbA1c (%) (p≤0.05), with the median HbA1c (%) being highest in the chemical taste dysfunction: sweet: yes group. Strength of association (Point- Biserial correlation)=0.49. There was a significant difference between the various groups in terms of distribution of chemical taste dysfunction: Sweet (p≤0.05). There was no significant difference between the groups in terms of duration of T2DM (years) (p&gt;0.05).Conclusion: The study found a significant correlation between taste dysfunction and HbA1C level and bloodsugar fasting level in type 2 diabetes mellitus patients. Alteration in taste was mainly for sweet. Sour, and bitter did not show any difference in case groups compared to controls.

Autonomic function and specific right atrial functions - Is there a relationship? Correlations from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study.

Similarly to the ventricles, the atria are under sympathetic/parasympathetic neural regulation. Accordingly, correlations were investigated between Ewing's standard cardiovascular reflex tests (SCRTs) and three-dimensional speckle-tracking echocardiography (3DSTE)-derived right atrial (RA) volumes and strains in healthy subjects. The study comprised 45 healthy adults, but 5 subjects were excluded due to inferior image quality for 3DSTE-derived RA assessments. The remaining 40 individuals being in sinus rhythm had a mean age of 35.1 ± 3.5 years (20 men). Two-dimensional, Doppler, 3DSTE and SCRTs were performed in all cases. RA maximum volume and total and passive RA stroke volumes correlated with the Valsalva ratio. Active RA stroke volume and emptying fraction showed correlations with 30/15 ratio. Peak global and mean segmental RA circumferential (CS) and longitudinal strains (LS) showed correlation with the Valsalva ratio. At atrial contraction, global RA-LS and mean segmental RA-CS showed correlations with the Valsalva ratio. Moreover, mean segmental RA-CS correlated with 30/15 ratio and mean segmental RA radial strain showed correlations with systolic blood pressure in response to standing. Autonomic neuropathy score correlated with peak global RA-LS. Autonomic function parameters have significant associations with specific RA functions in healthy adults, making the latter possible indicators of autonomic dysregulation.

High serum levels of CCL11/Eotaxin-1 are associated with diabetic sensorimotor polyneuropathy and peripheral nerve function but not with cardiac autonomic neuropathy in people with type 2 diabetes

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

Survey on electrocardiography signal analysis and diabetes mellitus: unraveling the complexities and complications

Electrocardiography (ECG) is crucial in the medical field to assess cardiovascular diseases. ECG signal generates information, i.e., QRS complexes that imply the cardiac health of the human body. It is depicted in the form of a graph with voltage versus time interval. A distorted, inverted, lagged, small waveform implies an abnormality in a cardiac system. This study highlights the generation of an ECG signal, QRS complexes undertoned towards different diseases, event detection, and signal processing methods. It has become crucial to highlight the possibilities and advances that can be derived from an ECG signal. Throughout this study, an instance of diabetes mellitus (DM) is considered for creating concrete awareness and understanding of an ECG signal in DM. This study focuses on finding the correlation between ECG and DM. Detection of DM from ECG signal is also studied. The findings of this survey paper conclude that the correlation between DM individuals with cardiovascular complications has autonomic neuropathy, which may lead to myocardial infarction. It is also found that the QRS complex and its abnormalities are not specific to complications in DM. However, non-invasive detection of diabetes through ECG signals demonstrates future research potential.

Bladder dysfunction in adolescents with type 1 diabetes

It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes. To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests. Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed. The main results are shown in the Summary figure. In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo etal. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system. In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction.

Congenital Insensitivity to Pain with Anhidrosis (CIPA): A Comprehensive Review

Abstract: Congenital Insensitivity to Pain with Anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is a rare genetic disorder characterized by the inability to perceive pain and a lack of sweat (anhidrosis). This review aims to provide a comprehensive understanding of CIPA, including its clinical features, genetic basis, diagnostic challenges, and management strategies.

The Importance of Evaluating Sudomotor Function in the Diagnosis of Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy (CAN) is a disorder affecting the autonomic nerves that regulate the cardiovascular system, leading to irregular heart rate and blood pressure control. It is commonly associated with diabetes mellitus but can also result from other conditions such as autoimmune disorders, chronic kidney disease, alcohol abuse, and certain medications. Screening for CAN is essential, particularly in individuals with poor glycemic control, cardiovascular risk factors, or complications. Early identification of CAN is vital for timely intervention to prevent or manage cardiovascular complications effectively. Regular screening helps detect CAN before symptoms emerge, enabling early intervention to slow or halt its progression. This study examined the relationship between sudomotor function and cardiovascular reflex tests. This was a cross-sectional study conducted between June 2019 and June 2020. The study included 271 subjects aged 18 years and above who provided informed consent, were diagnosed with type 2 diabetes mellitus (T2DM), and were overweight or obese. Exclusion criteria encompassed patients with other types of diabetes, pregnant women, those with recent neoplasm diagnoses, stroke sequelae, history of myocardial infarction, or pelvic limb amputations. The assessment of cardiac autonomic neuropathy involved conducting an electrocardiogram and evaluating the QTc interval in the morning before taking medication. Additionally, cardiovascular reflex tests (CART) were conducted, including assessments of heart rate variability during deep breathing, the Valsalva maneuver, and changes in orthostatic position. Simultaneously, the diagnosis of CAN was assessed by performing a sweat test using a Sudoscan assessment (Impeto Medical, Moulineaux, France). Results: More than half of the participants (52%, n=143) were female. Significant differences in statistical measures were noted between females and males regarding age, systolic blood pressure, fasting blood glucose, A1c level, total cholesterol, triglycerides, gamma-glutamyl transferase, and bilirubin levels. Within the CAN-diagnosed group (CAN+), 40.92% were classified as mild cases (n=90), 47.27% as moderate cases (n=104), and 11.81% as severe cases (n=26). Among the CAN+ group, 54% (n=119) were women. Electrochemical skin conductance was lower in the CAN+ group than the CAN- group in hands (67.34±15.51 μS versus 72.38±12.12 μS, p=0.008) and feet (73.37±13.38 μS versus 82.84 ±10.29 μS, p<0.001). The Sudoscan-CAN score significantly correlated with Ewing scores (r= 0.522, p<0.001). In multiple linear regression analysis, the Sudoscan-CAN score remained significantly associated with age, high BMI, long-standing diabetes, and Ewing score. Sudoscan demonstrates potential in identifying patients with an increased risk of CAN. Its integration into clinical practice can improve patient outcomes through early detection, risk stratification, and personalized treatment approaches. Its non-invasive, portable, and user-friendly features render it suitable for utilization in outreach programs or resource-constrained settings as part of screening efforts designed to pinpoint high-risk individuals for additional assessment.

Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial

Aims/hypothesisDiabetic 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.MethodsThis 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.ResultsSixty-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/interpretationCervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy.Trial registrationClinicalTrials.gov NCT04143269FundingThe study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045)Graphical

Impact of exercise on cardiovascular autonomic neuropathy

Impact of exercise on cardiovascular autonomic neuropathy

High dose cholecalciferol supplementation causing morning blood pressure reduction in patients with type 1 diabetes mellitus and cardiovascular autonomic neuropathy

We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017.

Rs4862705 in the melatonin receptor 1A gene is associated with renal function decline in type 1 diabetes individuals.

The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.