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ABSTRACT: Diabetic autonomic neuropathy is one of the most common complications of diabetes which is asymptomatic in early stage. Hence HRV and AFT are performed to detect and prevent its progression to advanced stages. To discuss the HRV and AFT findings in diabetic patients. An observational study was conducted in Physiology department of AIIMS, Bhopal in collaboration with the Medicine department of the institute. Seventy-two diagnosed Type-2 Diabetes mellitus patients were examined using POWER LAB AND LAB CHART 8 BY AD INSTRUMENT: For recording heart rate variability (HRV) and Ewing's battery of tests: For Autonomic function testing. Microsoft Excel was utilized for data compilation and for result analysis. In the present study, based on HRV parameters sympathetic involvement was seen in 39% while parasympathetic involvement was seen in 15% of patients. Balanced state was observed in 46% of the patients. Based on AFT battery, normal early involvement was observed in 62% of the patients while definite and severe involvement was observed in 14 and 24%, respectively. Diabetic autonomic neuropathy was observed in 72% of the patients based on HRV and AFT testing. In severe involvement, orthostatic hypotension was seen. Severe involvement was observed in 24% of the patients in present study. Involvement of the vagal parasympathetic component of ANS was obvious evidenced by increase in resting heart rate, decrease in Valsalva ratio, E/I index, and standing ratio. Diabetic autonomic neuropathy was observed in majority of patients with normal early involvement seen predominantly and though majority of them were in balanced state, sympathetic involvement was also seen at large. HRV studies depicted a decrease of total power, decreased low frequency (LF) and high frequency (HF) with LF/HF and SD1/SD2 ratios depicting sympathetic involvement. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusions & Inferences Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers.We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function.Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04–1.35), p = 0.01; GSRS: 1.15 (1.03–1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03–1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89–0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03–1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16–1.19), p = 0.03; GSRS: 0.87 (0.30–1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived. [ABSTRACT FROM AUTHOR]

Aims: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. Methods: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24‐week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. Results: Eighty‐three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement −1.2 [95% CI −0.8, −1.6]; p < 0.001). Conclusions: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility. [ABSTRACT FROM AUTHOR]

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations, leading to mitochondrial dysfunction, are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) poses a significant health-care challenge and is a primary contributor to both mortality and morbidity. Diabetic autonomic neuropathy (DAN) is a frequently occurring complication associated with diabetes mellitus. Autonomic nerve damage leading to cardiac autonomic dysfunction and peripheral sympathetic neuropathy can lead to changes in heart rate variability (HRV) and galvanic skin response (GSR), respectively. Aims and Objectives: The study was designed and done to evaluate the impact of T2DM on HRV and GSR for assessing DAN. Materials and Methods: A total of 100 individuals diagnosed with T2DM (cases) and 100 healthy individuals (controls) participated in this study. Physio Pac (PC-2004) was used to record the necessary data. Statistical analysis was performed using the non-parametric Mann--Whitney test to see the comparison of the cases and controls. In addition, to measure the statistical relationship between the duration of the disease and the HRV and GSR parameters, Spearman's rank correlation coefficient was utilized. The study received approval from the Ethical and Research Committee at the Government Medical College, Patiala. Results: Significant statistical differences were observed between the cases and controls in all time domain measures, as well as GSR and the majority of frequency domain measures of HRV. The correlation analysis revealed a strong association between the duration of T2DM and a decrease in HRV as well as an increase in GSR. Conclusion: The findings from the present study provide evidence that T2DM has an impact on HRV, which suggests the presence of cardiac autonomic neuropathy among diabetic patients, leading to an increased risk of cardiovascular morbidity. In addition, the study indicates that reduced sudomotor function, as assessed by galvanic skin response (GSR), serves as a predictive measure for autonomic neuropathy. Therefore, these tests can serve as valuable tools in facilitating the assessment of DAN. [ABSTRACT FROM AUTHOR]

A dangerous side effect of diabetes that can significantly lower quality of life and raise the death rate of diabetic individuals is diabetic autonomic neuropathy. It is essential to identify and anticipate this disease early on for prompt intervention and care. This study aims to predict this diabetic complication using Sudoscan and artificial intelligence. In this study, 172 individuals with type 1 or type 2 diabetes mellitus provided clinical and demographic information. Sudoscan was used to evaluate the subjects' sudomotor dysfunction. Statistical methods were used to link various electrochemical skin conductance values with risk factors for neuropathy such as age, BMI, age of diabetes, or biochemical values such as cholesterol and triglycerides. Different machine-learning algorithms were used to predict the risk of diabetic autonomic neuropathy based on the collected data. The accuracy achieved with Logistic Regression is 92.6%, and with the Random Forest model is 96.3%. Lazzy Classifiers also show that six classifiers have a high performance of 97%. Thus, the use of machine learning algorithms in this field of metabolic diseases offers new perceptions for diagnosis, treatment, and prevention, and improves the quality of life of diabetic patients by reducing the incidence of complications related to this disease. [ABSTRACT FROM AUTHOR]

Context: Prolonged pupil cycle time (PCT) is a complication of type II diabetes and becomes more protracted as the disease progresses. PCT can be used as a quick and accurate clinical test to determine how much autonomic neuropathy is influencing a diabetic patient’s pupil. Aims: The aim of the study was to compare the PCT of type II diabetes patients with that of the healthy control group and analyze the impact of several factors, including age, sex, duration of diabetes, and grade of diabetic retinopathy on PCT. Settings and Design: The study was conducted from August 2022 to August 2023. One hundred people were arbitrarily selected, 50 of whom had diabetes and 50 healthy controls. Subjects and Methods: To start rhythmic cycles of contraction and relaxation, a narrow, horizontally aligned beam of fixed proportions was focused on the inferior area of the pupil. The cycle period was then monitored in milliseconds using a handheld stopwatch. The mean PCT of diabetics was compared with nondiabetics and its correlation with different variables such as age, sex, diabetes duration, and grade of retinopathy was done. Results: Fifty diabetic patients (28 females and 22 males) aged 42–74 years and 50 controls (32 females and 18 males) aged 44–70 were included in the study. The mean PCT of the diabetics was 1130 ± 186 ms, whereas it was 940 ± 132 ms in the controls; thus, the mean PCT was longer in the diabetics. It was also found that the mean PCT increased with increasing grades of retinopathy. A positive correlation was also noted between mean PCT and duration of diabetes. Conclusions: PCT is a fast, simple, and reliable clinical test of optic nerve function. Being objective and quantifiable for each eye separately is a huge benefit. The PCT measurements might be used in the clinical evaluation of an autonomic nervous system. It is a simple, inexpensive yet quick, and effective tool to assess pupillary autonomic neuropathy in the diabetics.

Objective: The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. Design and Methods: For a cross‐sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal‐mediated glucose disposal (GIGD). Results: Sixty‐five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p =.005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = −0.204, p =.106), but an association was found with GIGD (rho −0.341, p =.005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. Conclusions: Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. Previously Published: Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658‐P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658–P. https://doi.org/10.2337/db23‐1658‐P. [ABSTRACT FROM AUTHOR]

A dangerous side effect of diabetes that can significantly lower quality of life and raise the death rate of diabetic individuals is diabetic autonomic neuropathy. It is essential to identify and anticipate this disease early on for prompt intervention and care. This study aims to predict this diabetic complication using Sudoscan and artificial intelligence. In this study, 172 individuals with type 1 or type 2 diabetes mellitus provided clinical and demographic information. Sudoscan was used to evaluate the subjects’ sudomotor dysfunction. Statistical methods were used to link various electrochemical skin conductance values with risk factors for neuropathy such as age, BMI, age of diabetes, or biochemical values such as cholesterol and triglycerides. Different machine-learning algorithms were used to predict the risk of diabetic autonomic neuropathy based on the collected data. The accuracy achieved with Logistic Regression is 92.6%, and with the Random Forest model is 96.3%. Lazzy Classifiers also show that six classifiers have a high performance of 97%. Thus, the use of machine learning algorithms in this field of metabolic diseases offers new perceptions for diagnosis, treatment, and prevention, and improves the quality of life of diabetic patients by reducing the incidence of complications related to this disease.

Abstract Objective The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. Design and Methods For a cross‐sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal‐mediated glucose disposal (GIGD). Results Sixty‐five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = −0.204, p = .106), but an association was found with GIGD (rho −0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. Conclusions Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. Previously Published Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658‐P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658–P. https://doi.org/10.2337/db23‐1658‐P.

Background and Aims: Cardiovascular autonomic neuropathy (CAN) in patients with diabetes is associated with poor prognosis. We aimed to assess signs of CAN and autonomic symptoms and to investigate the impact of sensorimotor neuropathy on CAN by examining type 2 diabetes patients with (DPN [distal sensorimotor polyneuropathy]) and without distal sensorimotor polyneuropathy (noDPN) and healthy controls (HC). Secondarily, we aimed to describe the characteristics of patients with CAN. Methods: A population of 374 subjects from a previously described cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) were included. Subjects were examined with the Vagus™ device for the diagnosis of CAN, where two or more abnormal cardiovascular autonomic reflex tests indicate definite CAN. Autonomic symptoms were assessed with Composite Autonomic Symptom Score 31 (COMPASS 31) questionnaire. DPN was defined according to the Toronto consensus panel definition. Results: Definite CAN was present in 22% with DPN, 7% without DPN and 3% of HC, and 91% of patients with definite CAN had DPN. Patients with DPN and definite CAN reported higher COMPASS 31 scores compared to patients with noDPN (20.0 vs. 8.3, p < 0.001) and no CAN (22.1 vs. 12.3, p = 0.01). CAN was associated with HbA1c and age in a multivariate logistic regression analysis but was not associated with IEFND or triglycerides. Interpretation: One in five patients with DPN have CAN and specific CAN characteristics may help identify patients at risk for developing this severe diabetic complication. Autonomic symptoms were strongly associated with having both DPN and CAN, but too unspecific for diagnosing CAN. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic autonomic neuropathy (DAN), a serious complication of diabetes, is a significant contributor to increased morbidity and mortality. Although DAN often coexists with different peripheral neuropathies and other complications, it may also present in isolation. The present study aimed to understand the DAN status of a cohort of ambulatory type 2 diabetics in a tertiary care setting. Methods: A single-arm prospective observational study was carried out, where enrolled patients were interviewed for basic demographics and comorbidities, screened for symptoms of autonomic dysregulation, and other risk factors such as smoking and alcoholism. Based on the presence of overt symptoms, they were divided into two groups with or without any overt symptoms of autonomic neuropathy. Both groups were subjected to a battery of autonomic neuropathy tests, and their DAN status was characterized based on the observed scores. Results: The overall prevalence of DAN, as observed in our study, was 36%. Of 108 patients, 97 presented with one or more symptoms of autonomic dysregulation, whereas the rest, 10.1%, were without any symptoms. Among heart rate-based tests, a significant (P < 0.001) decrease followed by an increase in the Valsalva ratio was observed in 6 months and 12 months, respectively. A significant decrease (P < 0.001) in deep breathing test (E: I) values was observed in the 12th month. Most of the DAN patients presented with moderate autonomic dysfunction, followed by mild and severe, respectively. However, no significant change in DAN severity was noted with time. Conclusion: Using simple cardiovascular tests, DAN can be detected during the asymptomatic phase of the disease. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is one of the most debilitating diseases, diabetic neuropathy happens to be the most common and perhaps the most serious complication of diabetes mellitus, often leading to morbidity and mortality. A 60 year old female presented with disorientation, history of vomiting, shortness of breath, respiratory failure initially. Blood reports revealed that she was positive for ketone bodies with elevated HbA1c and general random blood sugar. Chest radiogram revealed atelectasis of the right lung with prominent involvement of right middle and lower lobes. High-resolution computed tomography of chest confirmed the findings and unilateral diaphragmatic paralysis due to phrenic nerve neuropathy due to undetected type 2 diabetes was diagnosed. Although phrenic nerve paralysis is a rare occurrence with diabetes, the possibility shouldn't be overlooked as a presentation of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims: To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements. Methods: Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination. Results: CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%. Conclusion: This study suggests that CAN predominantly co-exists with concomitant DPN. [ABSTRACT FROM AUTHOR]

The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic. [ABSTRACT FROM AUTHOR]

Background: Patients who suffer from diabetic peripheral neuropathy in the lower leg experience a greater risk of falls due to a decrease in strength of the lower extremities. Methods: Fourteen participants, diagnosed with diabetic peripheral neuropathy or nocturnal allodynia in either one or both extremities, volunteered to participate in this study. Participants were purposively selected from two private Podiatry practices based on their signs and symptoms, age, gender, and doctor's clearance to participate in any form of physical activity. Dependent variables included isometric muscle strength of the hip, knee and ankle, range of motion of the ankle in plantarflexion and dorsiflexion and an assessment of balance, which were measured pre- and post-intervention. The researcher developed a scientifically based exercise intervention program to target the entire kinetic chain, and to develop a standard isometric protocol for patients with DPN. The intervention program consisted of a combination of ankle, hip, and knee specific rehabilitation. The intervention took place 3 times a week for 45 min per session. Results: The Mann-Whitney test was used to evaluate the differences in dependent variables from pre- to post-intervention. The level of significance was set at p<0.05. Notable increases were observed in range of motion in ankle plantarflexion and in balance time in the intervention group, post-intervention. Conclusions: Although many of the changes noted were insignificant, the trends indicated an improvement in the intervention group over the 10-week intervention period. These improvements can be considered clinically important. [ABSTRACT FROM AUTHOR]

Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD. [ABSTRACT FROM AUTHOR]

The progression of autonomic dysfunction from peripheral autonomic neuropathy (PAN) to cardiovascular autonomic neuropathy, including diabetic autonomic neuropathy and advanced autonomic dysfunction, increases morbidity and mortality risks. PAN is the earliest stage of autonomic neuropathy. It typically involves small fiber disorder and often is an early component. Small fiber disorder (SFD) is an inflammation of the C-nerve fibers. Currently, the most universally utilized diagnostic test for SFD as an indicator of PAN is galvanic skin response (GSR), as it is less invasive than skin biopsy. It is important to correlate a patient’s symptoms with several autonomic diagnostic tests so as not to treat patients with normal findings unnecessarily. At a large suburban northeastern United States (Sicklerville, NJ) autonomic clinic, 340 consecutive patients were tested with parasympathetic and sympathetic (P&S) monitoring (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) with cardiorespiratory analyses, and TMFlow (Omron Corp., Hoffman Estates, Chicago, IL, USA) with LD Technology sudomotor test (SweatC™). This is a prospective, nonrandomized, observational, population study. All patients were less than 60 y/o and were consecutively tested, analyzed and followed from February 2018 through May 2020. P&S Monitoring is based on cardiorespiratory analyses and SweatC™ sudomotor testing is based on GSR. Overall, regardless of the stage of autonomic neuropathy, SweatC™ and P&S Monitoring are in concordance for 306/340 (90.0%) of patients from this cohort. The result is an 89.4% negative predictive value of any P&S disorder if the sudomotor GSR test is negative and a positive predictive value of 90.4% if the sudomotor testing is positive. In detecting early stages of autonomic neuropathy, P&S Monitoring was equivalent to sudomotor testing with high sensitivity and specificity and high negative and positive predictive values. Therefore, either testing modality may be used to risk stratify patients with suspected autonomic dysfunction, including the earliest stages of PAN and SFD. Moreover, when these testing modalities were normal, their high negative predictive values aid in excluding an underlying autonomic nervous system dysfunction.

Diabetic autonomic neuropathy (DAN) is an individual risk factor for nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, other major cardiovascular events like hospitalization for angina, hospitalization for heart failure, urgent revascularization for unstable angina, and death from any cause. Diabetic autonomic neuropathy screening is of paramount importance for cardiovascular risk stratification in patients with and without cardiovascular disease; as a marker for patients requiring more intensive monitoring during the perioperative period and other physiological stresses; and as an indicator for more intensive pharmacotherapeutic and lifestyle management of comorbid conditions. The present review highlights the necessity of DAN screening in starting cardiovascular outcome trials for antidiabetic agents.

Diabetic cystopathy is a condition characterized by decreased bladder sensitivity, increased bladder capacity, decreased bladder contractility and increased residual urine volume. It can also be considered as an early indicator of autonomic dysfunction. In this study, it was aimed to evaluate bladder functions by uroflowmetry in children and adolescents with the diagnosis of type 1 diabetes mellitus. Type 1 diabetes mellitus children and adolescents were applied uroflowmetry and post-void residual urine volumes were evaluated. The physical examination findings of the patients and the laboratory data of diabetes control were obtained from the clinic files. A total of 51 cases aged 72–216 (155.6 ± 35.4) months were enrolled into the study. Diabetes age of the cases was 66.5 ± 46.2(13–180) months. The last one year average of HbA1c of the patients was found to be 9.7 ± 1.9%. A total of 9.8% had good, 39.2% moderate and 51% poor metabolic control, respectively. While urodynamic evaluation was normal in 36 (70.6%) of 51 participants, voiding dysfunction was found in 15. There was no statistically significant difference between groups with and without voiding dysfunction in terms of age, gender, duration of diabetes, metabolic control and HbA1c values. It is very important to follow up patients with type 1 diabetes mellitus in terms of autonomic dysfunction. Diabetic bladder clinic, which can be observed independently of diabetes duration and metabolic control, is also included in this status. Urodynamic evaluation will be helpful both in demonstrating bladder dysfunction and in preventing possible complications. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cardiac autonomic neuropathy (CAN) encompasses damage to the autonomic nerve fibres that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. The reported prevalence of CAN varies depending on the clinical setting, type and number of tests performed, different diagnostic methods applied, and selection criteria for the patients. Studies using different end points have reported prevalence estimates ranging from 1% to 90%. Hence we studied CAN in T2DM patients and attempted to see the correlation between the two along with glycaemic control and QT ratio in CAN. Materials and Methods: The study was conducted on 100 type2 diabetes subjects meeting inclusion and exclusion criteria. Subjects were tested for five cardiac autonomic neuropathy tests, HbA1c levels and ECG with reference to QT ratio. Results: In our study 60% were asymptomatic and 40% were symptomatic for diabetic autonomic neuropathy(DAN) symptoms. 32% of asymptomatic DAN patients had early CAN. Patients who had absent, early and definite CAN were 28%, 44% and 28% respectively. Majority of patients in absent CAN group (15%) were having DM less than 5yr duration. In definite CAN group (20%) were having above 10yr duration. Stages of CAN is directly associated with duration of diabetes which is statistically significant (P value: <0.001). Among 28 patients who had definite CAN, corrected QTc was prolonged in 22 patients. Conclusion: 32% of asymptomatic DAN patients had early CAN. Poorly controlled diabetic state group had CAN in 82% of the subjects concluding that stages of CAN is directly related to the duration of diabetes. QTc dispersion was significantly high in diabetics with autonomic neuropathy. [ABSTRACT FROM AUTHOR]

Yiying Liu,1,&ast; Xin Wang,2,&ast; Linying Wang,1 Wenwen Chen,3 Wenyue Liu,1 Tingting Ye,1 Jing Hong,1 Hong Zhu,1 Feixia Shen1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People’s Republic of China; 3Department of Senile Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feixia ShenDepartment of Endocrinology and Metabolism, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaEmail shenfeixia@wmu.edu.cnPurpose: Diabetic neurogenic bladder (DNB) has been widely recognized in recent years. It is common in patients with long-term diabetes and may also lead to many severe complications. Although there has been widespread evidence that inflammation is involved in the development of some diabetic complications, there is little evidence that this can also occur in the bladder. In recent years, platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have been viewed as potential novel markers of inflammatory responses. This study was designed to evaluate the relationship between the presence of DNB and the PLR and NLR.Patients and Methods: A total of 371 cases of T2DM patients were included in this retrospective study. Patients were divided into two groups, with 115 diabetic subjects diagnosed with diabetic neurogenic bladder and 256 control subjects without DNB. The independent predictors of DNB were analyzed using logistic regression.Results: Compared with patients without DNB, the mean PLR and NLR were significantly higher in those with DNB (p < 0.001). Based on the logistic regression, PLR was found to be an independent risk factor for DNB (odds ratio [OR]: 1.408, 95% confidence interval [CI]: 1.248– 1.617). From the receiver operating characteristic (ROC) curve, using PLR as indicative of DNB was expected to be 101.1949, and it generated a sensitivity and specificity value of 89.6% and 23.4%, respectively. The area under the curve (AUC) was also found to be 0.899 (95% CI: 0.865– 0.932).Conclusion: In our study, PLR and NLR were significantly higher for patients with DNB. The PLR was found to be a risk factor in the presence of DNB after correcting for possible confounding factors. Considering the severe complications associated with DNB, patients with elevated PLR should be seriously cared for in clinics.Keywords: diabetic autonomic neuropathy, neurogenic bladder, oxidative stress, inflammatory response

Gastroparesis is known as delayed gastric emptying in the absence of mechanical obstruction, typical symptoms being nausea, vomiting, bloating, early satiety, and upper abdominal pain. Gastroparesis is much prevalent in type 2 diabetes mellitus patients. Currently, methods used for the assessment of gastrointestinal (GI) motility involve radiation and invasiveness and are mostly limited to regional assessment, with a lengthy hospital stay, and most of the tests are even not standardized. Gastric emptying scintigraphy (GES) using a radiolabeled meal is the gold standard diagnostic test used to detect and quantify gastroparesis. The advantages of this test are physiological, economical, and non-invasive characteristics. However, lack of standardization poses radiation exposure. As diabetic patients already suffer from diabetic complications and comorbidities, availability of diagnostic tests by offering a non-radioactive, standardized, and ambulatory investigation may be a better alternative to GES to prevent unnecessary radiation exposure. This review summarizes the role of wireless motility capsule (WMC) in diagnosing gut diabetic autonomic neuropathy. The WMC is a novel technology that allows the physician to measure GI motility in a convenient, ambulatory, relatively non-invasive way, without exposing the patient to radiation. The WMC also established its diagnostic utility to assess diabetic gastroparesis in many multicentric studies; although it has some contraindications and limitations, it is the best available novel technology for diagnosing gut diabetic autonomic neuropathy.

Samyukta Bista Karki,1 Kirsten J Coppell,2 Logan V Mitchell,2 Kelechi C Ogbuehi2 1Drishti Eye Care Center, Kathmandu 44600, Nepal; 2Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9054, New ZealandCorrespondence: Kelechi C OgbuehiDepartment of Medicine, Dunedin School of Medicine, University of Otago, 201 Great King Street, Dunedin 9054, New ZealandTel +64 3 474 0999 Ext 58308Email kelechi.ogbuehi@otago.ac.nzPurpose: Autonomic dysfunction may precede the microvascular changes that characterise diabetic retinopathy. The aim of this pilot study was to measure and compare pupillometry indices in type 2 diabetes (T2DM) patients – with and without diabetic retinopathy – and in healthy, age-matched controls.Methods: Two hundred and eleven participants with T2DM aged 45– 80 years were recruited from Dunedin Hospital Eye Department, Dunedin, New Zealand. They were categorised into three groups – no, mild/moderate, or severe diabetic retinopathy. Seventy age-matched, diabetes screen negative control participants were recruited from the Dunedin city community. Dynamic pupillometry was performed using an infrared pupillometer. The main outcome measures were maximum constriction velocity, average constriction velocity, absolute constriction amplitude, relative reflex amplitude, average dilation velocity and 75% re-dilation (recovery) time. Outcome measures were compared between study groups using the Kruskal–Wallis nonparametric test (with Dunn’s multiple comparison post-test).Results: Pupillary parasympathetic function differed between groups. Maximum constriction velocity (p < 0.001) and average constriction velocity (p < 0.001) were slower, and absolute constriction amplitude (p < 0.001) and relative reflex amplitude (p < 0.05) were lower in the three diabetes groups compared with controls. There were no significant differences in pupillary sympathetic function between the four groups for re-dilation time, but the diabetes groups had significantly slower average dilation velocity times.Conclusion: Pupillary light reflex is significantly impaired with diabetic retinal neuropathy, before clinically observable signs of diabetic retinopathy. Dynamic pupillometry may be a cheap, clinically relevant test, but sensitivity and specificity need to be determined before utilising as a screening tool for diabetic retinopathy.Keywords: diabetic autonomic neuropathy, diabetic retinopathy, diabetic macular oedema, pupillary reflex, parasympathetic nervous system, type 2 diabetes mellitus

Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.

Background: In general, hypoglycemia is more frequent among the young explaining the higher frequency of impaired awareness of hypoglycemia (IAH) among children and adolescents. Thus the aim of the current study was to assess the frequency of IAH among an Egyptian cohort of children and adolescents with type 1 diabetes and identify the possible association between impaired awareness of hypoglycemia and autonomic neuropathy. Patients and Methods: A cross sectional study recruiting 100 patients with type 1 diabetes for at least 6 months duration and aged less than 18 years old recruited from the Pediatric and Adolescent Diabetes Unit (PADU). Patients with other form of diabetes, cardiac disease, thyroid disease, anemia, other chronic disease, patients with intellectual disabilities or patients taking any medications were excluded from the study. The Gold and Clarke questionnaires were used to assess hypoglycemia awareness among the studied cohort. Cardiac autonomic neuropathy (CAN) was assessed using 15 minutes Holterelectrocardiography (ECG). Results: Among the studied cohort, 42% showed IAH using the Clarke's and Gold's Questionnaires. When assessing CAN, 46% of the studied cohort showed resting tachycardia and patients with resting tachycardia showed significantly longer disease duration. There were no normative heart rate variability parameters values for the Egyptian children that can be used as a reference for diagnosis of cardiac autonomic neuropathy. So we used sex and age matched control group to find specific cutoff values for heart rate variability parameters to diagnose CAN. The results showed that the prevalence of CAN among studied- patients was 88% and there were no significant correlation between CAN and both questionnaires score. 55.7% of CAN patients were aware while 44.3% were unaware. Thus, there were no association between impaired awareness of hypoglycemia and CAN. The results showed that there was significant positive correlation between cardiac autonomic neuropathy (CAN) and diabetic duration more than 5 years. Conclusion: Although there were no association between impaired awareness of hypoglycemia and cardiac autonomic neuropathy, it is important to screen for CAN in patients with IAH, especially that CAN is usually asymptomatic among children with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Cardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in patients with diabetes as it is associated with a high risk of cardiac arrhythmias. Objectives: This prospective observational cross-sectional study was done to estimate the prevalence of CAN in patients with type 2 diabetes and to study its association with serum omentin and leptin levels. Methods: This study included 100 patients with type 2 diabetes mellitus attending the outpatient department of JIPMER Hospital, Pondicherry, India, from January 2017 to December 2018. CAN was assessed in all subjects using four cardiovascular autonomic function tests. Blood samples were collected and stored at - 80°C to estimate leptin and omentin levels. Comparison of leptin and omentin levels was done between diabetic patients with and without CAN. Results: CAN was present in 64% of the study subjects. Serum leptin levels were significantly higher in patients with CAN, whereas omentin levels, though elevated in those with CAN, were not statistically significant in diabetic patients without CAN. Conclusion: There is a high prevalence of CAN in patients with type 2 diabetes mellitus. Leptin levels were elevated in these patients, whereas omentin levels were not significantly different between diabetic patients with and without CAN.

Maryam Vasheghani,1 Farzaneh Sarvghadi,2 Mohammad Reza Beyranvand31Endocrinology & Metabolism Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Endocrinology & Metabolism Department, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Interventional Cardiology, Department of Cardiology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranIntroduction: Cardiac autonomic neuropathy (CAN) is one of major complications of diabetes mellitus (DM) that increases the risk of cardiovascular disorders, abnormal ventricular depolarization with poor prognosis as well as increased mortality and morbidity. Indeed, CAN has close relation with blood glucose level in diabetic patients. We investigated the relation of CAN with diabetes control.Materials and methods: Totally, 115 diabetic patients (mean age 50.87±13.90 years old; 78 females) underwent study. All patients had DM and cardiac sinus rhythm. Nobody had sickness affecting cardiac rhythm and blood pressure. In addition, they did not take drugs that had effect on blood pressure, cardiac rhythm, and QT interval. Forty-six patients had tight and 69 patients had uncontrolled DM according to American Diabetes Association (ADA) criteria. The CAN was assessed based on heart rate variation during physical examination (at rest tachycardia and orthostatic hypotension) and standard Ewing’s tests (deep-breathing and laying-to-standing tests) with bedside continuous ECG recording. The P-value

Introduction: In India, the prevalence of gallstones is considered as a major public health problem and among diabetic patients the prevalence is still more increasing. Presence of Diabetic Autonomic Neuropathy (DAN) is a triggering factor for gallbladder diseases among diabetic patients. Aim: To compare the gallbladder volume and contraction index between diabetic patients and non diabetic healthy controls. Materials and Methods: A cross-sectional study was conducted in a tertiary care hospital at Chennai for a period of six months from June 2019 to December 2019. The total 90 subjects were divided into two groups of 45 each, group A consist of 45 known Type I or Type II diabetes mellitus (DM)and group B with 45 non diabetic healthy controls. The gallbladder volume was assessed initially in the fasting state, then the patient was asked to have fatty meal and again the gallbladder volume was measured after two hours for all the patients and the gallbladder contraction index was calculated using these values. Autonomic neuropathy grading was done after performing neuropathy assessment tests and the association between the gallbladder contraction index and grading of autonomic neuropathy was analysed. Results: The mean fasting and postprandial gallbladder volume were much higher among diabetic patients compared to non diabetic controls and similarly the gallbladder contraction index was lesser among diabetic patients compared to the controls (16.6±5.9 cm3 , 4.03±1.8 cm3 ) and (32.08±11.7 cm3 , 17.4±10.6 cm3 ) the difference was found to be statistically significant (p-value

Purpose: We aimed to reveal whether static and dynamic pupillary responses can be used for the detection of autonomic nervous system (ANS) dysfunction in patients with obstructive sleep apnea syndrome (OSAS). Methods: We included in this study patients with OSAS, who were divided into three groups according to the apnea–hypopnea index (AHI) (group 1, mild [n = 20]; group 2, moderate [n = 20]; and group 3, severe [n = 20]), and healthy controls (group 4, n = 20). Pupillary responses were measured using a pupillometry system. Results: Static (mesopic PD, P = 0.0019; low photopic PD, P = 0.001) and dynamic pupil responses (resting diameter, P = 0.004; amplitude of pupil contraction, P < 0.001; duration of pupil contraction, P = 0.022; velocity of pupil contraction, P = 0.001; and velocity of pupil dilation, P = 0.012) were affected in patients with different OSAS severities. Also, AHI was negatively correlated with mesopic PD (P = 0.008), low photopic PD (P = 0.003), resting diameter (P = 0.001), amplitude of pupil contraction (P < 0.001), duration of pupil contraction (P = 0.011), velocity of pupil contraction (P < 0.001), and velocity of pupil dilation (P = 0.001). Conclusion: We detected pupil responses innervated by the ANS were affected in the OSAS patients. This effect was more significant in the severe OSAS patients. Therefore, the pupillometry system can be an easily applicable, noninvasive method to detect ANS dysfunction in the OSA patients. [ABSTRACT FROM AUTHOR]

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing's test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing's test, and HRV in diagnosing DAN.Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing's test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(–) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman's correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method.Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing's test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing's test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing's test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing's test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses.Conclusions: COMPASS-31 and Ewing's test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up.

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing's test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing's test, and HRV in diagnosing DAN. Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing's test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(–) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman's correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method. Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing's test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing's test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing's test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing's test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses. Conclusions: COMPASS-31 and Ewing's test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up. [ABSTRACT FROM AUTHOR]

A 51-year-old man with type 2 diabetes mellitus was admitted with a 2-month history of repeated episodes of transient aphasia and right hemiparesis after food intake. His blood pressure (BP) fell when the neurological deficits developed. The fall in BP after each meal was confirmed by 24-h ambulatory blood pressure monitoring (ABPM), which established the diagnosis of postprandial hypotension (PPH). Diffusion-weighted magnetic resonance imaging of the brain showed multiple high-intensity lesions at the borderzone between the anterior and middle cerebral artery (MCA) territories in the left hemisphere. Digital subtraction angiography showed tapered occlusion at the origin of the left internal carotid artery (ICA). Despite sufficient antiplatelet therapy and medication for PPH, the transient symptoms remained. Positron emission tomography scanning using H215O showed decreased cerebral blood flow with increased oxygen extraction fraction in the left MCA territory. As the symptomatic left ICA occlusion was intractable, an extracranial-intracranial (EC-IC) bypass surgery was conducted without any perioperative complications. Although PPH remained, cerebrovascular ischemic events including repeated transient ischemic attack disappeared for 2 months after surgery. The coincidence of stroke with ABPM-proved transient hypotension suggested that the brain infarcts were caused by hemodynamic changes related to PPH co-existent with the chronic left ICA occlusion. ABPM is useful in evaluating hemodynamic infarcts associated with BP fluctuation, and should be considered for patients with chronic ICA occlusion. In addition, EC-IC bypass may be a treatment option for symptomatic chronic ICA occlusion due to PPH.

Abstract Background Autonomic neuropathy (AN) commonly arises as a long‐term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context. Methods A total of 167 individuals 6–60 years old (113 with T1DM and 54 healthy controls) underwent 24‐hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary. Results Heart rate variability (high‐frequency power during sleep) was reduced (p

Purpose: To investigate the relation between erectile dysfunction (ED) severity and pupillary functions in patients with diabetes mellitus (DM). Methods: This prospective and observational study included 90 patients with type 2 DM and ED. Patients divided into three subgroups according to severity of ED: (i) Mild ED, (ii) Moderate ED and (iii) Severe ED groups. Thirty age-matched healthy subjects formed the control group. Main outcome measures were pupil diameter and average speed of pupil dilation. Static and dynamic pupillometry analysis was performed using the Sirius Topographer (CSO, Firenze, Italy). Results: Mean pupil diameter during static and dynamic pupillometry analysis were significantly greater in the control group than in the all study groups (P < 0.05). Mean pupil diameter in static pupillometry analysis was significantly different in each study group and pupil was more miotic in the Severe ED group than in the both Moderate and Mild ED groups (P < 0.05 for each). Dynamic pupillometry analysis revealed that mean pupil diameter and mean average dilation speed were significantly different in each study group throughout measurement period and the highest speed was observed in the Mild ED group and the lowest speed was observed in the severe ED group (P < 0.005 for each). Conclusion: Our study results suggest that abnormal pupil functions due to diabetic autonomic neuropathy may indicate the associated ED in patients with DM.

Abstract Background Disordered sleep breathing is a common complication of diabetic peripheral neuropathy (DPN) manifested by excessive daytime sleepiness, morning headache, morning dizziness, cognitive decline, and mood changes. Methods This study was performed on 30 non-obese type 2 diabetic patients; 20 with clinically evident DPN and 10 without. Ten age-, sex-, and body mass index-matched healthy control subjects were also included. Patients and control were subjected to history taking, neurological examination, glycated hemoglobin, and clinical assessment of the sensori-motor manifestations by the neuropathy symptom score and neuropathy disability score. The autonomic nervous system was evaluated clinically by the systolic blood pressure response to standing and heart rate response to each of standing, Valsalva, and deep breath. Finally, sleep was assessed by one-night polysomnogram (PSG) followed by multiple sleep latency test in the next day. Results The study showed significant increase in sleep apnea syndromes in diabetic peripheral neuropathy patients compared to diabetic neuropathy free patients and healthy control (p

• Sensitive, validated, noninvasive electrodiagnostic tests of autonomic function have been developed. • An international expert panel provides evidence-based recommendations to guide autonomic testing. • Recommendations allow for standardized assessment of severity and distribution of autonomic failure. Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis. [ABSTRACT FROM AUTHOR]

Diabetic neuropathies are the most common type of neuropathies seen in clinical practice. These neuropathies can range clinically from asymptomatic to manifesting symptoms caused by motor, sensory, and autonomic nerve dysfunction. These neuropathies can affect the peripheral nervous system, pain receptors, cardiovascular, urogenital, and gastrointestinal systems. This monograph presents an overview of the different types of diabetic neuropathies, their presentations, diagnostic tools, and strategies for management. [ABSTRACT FROM AUTHOR]

Purpose: Autonomic dysfunction may precede the microvascular changes that characterise diabetic retinopathy. The aim of this pilot study was to measure and compare pupillometry indices in type 2 diabetes (T2DM) patients – with and without diabetic retinopathy – and in healthy, age-matched controls. Methods: Two hundred and eleven participants with T2DM aged 45– 80 years were recruited from Dunedin Hospital Eye Department, Dunedin, New Zealand. They were categorised into three groups – no, mild/moderate, or severe diabetic retinopathy. Seventy age-matched, diabetes screen negative control participants were recruited from the Dunedin city community. Dynamic pupillometry was performed using an infrared pupillometer. The main outcome measures were maximum constriction velocity, average constriction velocity, absolute constriction amplitude, relative reflex amplitude, average dilation velocity and 75% re-dilation (recovery) time. Outcome measures were compared between study groups using the Kruskal–Wallis nonparametric test (with Dunn's multiple comparison post-test). Results: Pupillary parasympathetic function differed between groups. Maximum constriction velocity (p < 0.001) and average constriction velocity (p < 0.001) were slower, and absolute constriction amplitude (p < 0.001) and relative reflex amplitude (p < 0.05) were lower in the three diabetes groups compared with controls. There were no significant differences in pupillary sympathetic function between the four groups for re-dilation time, but the diabetes groups had significantly slower average dilation velocity times. Conclusion: Pupillary light reflex is significantly impaired with diabetic retinal neuropathy, before clinically observable signs of diabetic retinopathy. Dynamic pupillometry may be a cheap, clinically relevant test, but sensitivity and specificity need to be determined before utilising as a screening tool for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare static and dynamic pupil responses of diabetic patients with and without nonproliferative diabetic retinopathy (DR) and normal healthy individuals under different lighting conditions via quantitative automated pupillometry. Methods: Forty patients with DM with nonproliferative DR (group 1), 40 patients with DM without DR (group 2), and 40 healthy controls (group 3) underwent a complete ophthalmologic examination. Static pupillometry [scotopic pupil diameter (PD), mesopic PD, low photopic PD, and high photopic PD] and dynamic pupillometry (resting PD, contraction amplitude, latency, duration, velocity of contraction, dilatation latency, and duration and velocity at rest) were measured via automatic quantitative pupillometry. Results: Analysis of variance revealed that scotopic PD [F(2, 117) = 6.42; p = 0.02], mesopic PD [F(2, 117) = 3.20; p = 0.04], and low photopic PD [F(2, 117) = 4.86; p = 0.009] were significantly different among the groups. Scotopic PD and low photopic PD were significantly lower in group 1 than in group 2 (p = 0.03 and p = 0.03, respectively). Meanwhile, the resting diameter, velocity of pupil contraction, and velocity of pupil dilatation were found to be significantly lower (p = 0.02, p = 0.01, and p = 0.008, respectively), and the duration of pupil contraction was significantly higher in group 1 than in group 3 (p = 0.03). Conclusion: Both DM patients with and without nonproliferative DR exhibited pupillary involvement. Automated pupillometry may be an easily applicable, noninvasive screening option for reducing mortality and morbidity rates associated with diabetic autonomic neuropathy. [ABSTRACT FROM AUTHOR]

Background: Autonomic neuropathy (AN) commonly arises as a long-term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context.Methods: A total of 167 individuals 6-60 years old (113 with T1DM and 54 healthy controls) underwent 24-hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary.Results: Heart rate variability (high-frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes.Conclusion: Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol. [ABSTRACT FROM AUTHOR]

Cardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in patients with diabetes as it is associated with a high risk of cardiac arrhythmias. Objectives: This prospective observational cross-sectional study was done to estimate the prevalence of CAN in patients with type 2 diabetes and to study its association with serum omentin and leptin levels. Methods: This study included 100 patients with type 2 diabetes mellitus attending the outpatient department of JIPMER Hospital, Pondicherry, India, from January 2017 to December 2018. CAN was assessed in all subjects using four cardiovascular autonomic function tests. Blood samples were collected and stored at - 80°C to estimate leptin and omentin levels. Comparison of leptin and omentin levels was done between diabetic patients with and without CAN. Results: CAN was present in 64% of the study subjects. Serum leptin levels were significantly higher in patients with CAN, whereas omentin levels, though elevated in those with CAN, were not statistically significant in diabetic patients without CAN. Conclusion: There is a high prevalence of CAN in patients with type 2 diabetes mellitus. Leptin levels were elevated in these patients, whereas omentin levels were not significantly different between diabetic patients with and without CAN. [ABSTRACT FROM AUTHOR]

Diabetic autonomic neuropathy is an under-recognised complication of diabetes and the prediabetic state. A wide range of manifestations can be seen due to involvement of cardiovascular, gastrointestinal, genitourinary, sudomotor and neuroendocrine systems. Cardiac autonomic neuropathy is the most dreaded complication carrying significant mortality and morbidity. Early detection and control of diabetes and other cardiovascular risk factors is the key to treat and prevent progression of autonomic neuropathy. Recently, a new entity of treatment-induced neuropathy (TIND) of diabetes mellitus causing autonomic neuropathy is being increasingly recognised. [ABSTRACT FROM AUTHOR]

Diabetes mellitus has multiple negative effects on regenerative processes, especially on wound and fracture healing. Despite the well-known negative effects of diabetes on the autonomous nervous system, only little is known about the role in bone regeneration within this context. Subsequently, we investigated diabetic bone regeneration in db−/db− mice with a special emphasis on the sympathetic nervous system of the bone in a monocortical tibia defect model. Moreover, the effect of pharmacological sympathectomy via administration of 6-OHDA was evaluated in C57Bl6 wildtype mice. Diabetic animals as well as wildtype mice received a treatment of BRL37344, a β3-adrenergic agonist. Bones of animals were examined via µCT, aniline-blue and Masson–Goldner staining for new bone formation, TRAP staining for bone turnover and immunoflourescence staining against tyrosinhydroxylase and stromal cell-derived factor 1 (SDF-1). Sympathectomized wildtype mice showed a significantly decreased bone regeneration, just comparable to db−/db− mice. New bone formation of BRL37344 treated db−/db− and sympathectomized wildtype mice was markedly improved in histology and µCT. Immunoflourescence stainings revealed significantly increased SDF-1 due to BRL37344 treatment in diabetic animals and sympathectomized wildtypes. This study depicts the important role of the sympathetic nervous system for bone regenerative processes using the clinical example of diabetes mellitus type 2. In order to improve and gain further insights into diabetic fracture healing, β3-agonist BRL37344 proved to be a potent treatment option, restoring impaired diabetic bone regeneration.

Amaç: Tip 2 diabetes mellituslu (DM) hastalarda gastrointestinal ve kardiyovasküler diyabetik otonomik nöropatinin değerlendirilmesi amaçlanmaktadır. Materyal ve Metot: DM hastalarından oluşan çalışma grubu Mart-Eylül 2012 tarihleri arasında incelendi. Yaş, vücut kütle indeksi (VKİ), açlık kan glukozu, HbA1c, C-peptid, diyabet süresi, elektrokardiyogram, kan basıncı, kalp hızı kaydedildi. Hastalar kontrol altında olan ve olmayan diyabetikler olarak gruplandırıldı. Kardiyak otonom nöropati (KON) testleri değerlendirildi. Anal manometri ile rekto-anal inhibitör refleks, istirahat ve sıkma basınçları ölçüldü.Bulgular: Toplam 50 DM hastası çalışmaya kaydedildi ve hastaların yaş ortalaması 57,06±8,92 yıl, istirahat anal basıncı ortalaması 55,92±14,84 mmHg ve sıkma anal basıncı ortalaması 83,15±31,00 mmHg idi. Orta ve ağır KON grupları arasında istirahat anal basıncında anlamlı fark saptanmazken (p=0,573), orta ve ağır KON grupları arasında maksimum sıkma basıncında anlamlı fark mevcuttu (p=0,005). Kısa veya uzun süreli diyabeti olan hastalarda anal manometrik basınçlarda fark saptanmadı. KON ile VKİ arasında ilişki bulunmazken yaş ile ilişki saptandı. Kötü glisemik kontrol istirahat basında azalma ile ilişkili iken, maksimum sıkma basıncı ve yetersiz glisemik kontrol grubu arasında ilişki yoktu. KON’un şiddeti maksimum sıkma basıncında azalma ile ilişkiliydi. Sonuç: Kardiyak ve gastrointestinal otonom disfonksiyon, DM’nin önemli komplikasyonlarıdır. Anal manometri testleri ve KON diyabetin bu komplikasyonlarını gösterebilir.

Aim: Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods: Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results: Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions: Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.

Introduction: Diabetic autonomic neuropathy (DAN) is a prevalent yet often overlooked complication of diabetes mellitus (DM), impacting multiple organs and substantially elevating the risk of morbidity and mortality. This study aimed to assess the effectiveness of yoga-based intervention (YBI) compared to the American Diabetes Association exercise regimen (ADA Ex. Regime) and standard care for treating autonomic neuropathy in type 2 DM., Methods: This open-label exploratory clinical trial featured two parallel study arms: Group A (Intervention), which received YBI alongside standard care, and Group B, which adhered to the ADA Ex. Regime in conjunction with standard care. A total of 80 participants aged 35-60, diagnosed with type 2 DM and autonomic neuropathy, were equally allocated to both groups. Data collection included nerve conduction velocity (NCV) tests, autonomic function tests (AFTs), as well as evaluations of depression and quality of life., Results: YBI demonstrated a drop in parasympathetic tone compared to the ADA Ex. Regime. Following a six-month intervention, the sympathetic activity indicator (SD2) exhibited a significantly lower value in the YBI group than in the ADA Ex. Regime group, indicating a positive effect (p < 0.05), while the ADA Ex. Regime showed more improvement in certain areas of NCV (e.g., left and right peroneal NCV, right and left peroneal F-latency), notable differences were observed in alkaline phosphatase levels, depression scores, and WHO-5 wellness, all reaching statistical significance at p < 0.05., Conclusions: The study findings observed that a 24-week YBI significantly reduced in symptoms of diabetic neuropathy and stress. Although the ADA Ex. Regime demonstrated greater improvement in specific aspects of NCV compared to YBI, YBI outperformed the ADA Ex. Regime in enhancing WHO-5 wellness and reducing depression symptoms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institute Ethics Committee, All India Institute of Medical Sciences, Rishikesh issued approval AIIMS/IEC/21/617. CTRI Registration Number: CTRI/2021/12/039068. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)