Definite Cardiac Autonomic Neuropathy Research Articles

Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial.

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. 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. 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). 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.

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.

Evaluation of association between time in range, a continuous glucose monitoring metric, and cardiac autonomic neuropathy in type 2 diabetes patients.

Time in range (TIR), a metric of continuous glucose monitoring (CGM) provides better information regarding the individual's glycemic variability than a static measure like glycated hemoglobin (HbA1c). TIR is emerging as an independent risk factor for diabetic complications, both microvascular and macrovascular complications independent of HbA1c. Hence, this study evaluates the association between TIR and cardiac autonomic neuropathy (CAN) in type 2 diabetic patients. A total of 42 patients with type 2 diabetes mellitus were enrolled in this study and underwent a 3-day CGM using the "FreeStyle Libre Pro Flash Glucose Monitoring System Sensor" along with tests for CAN within the 3 days of attaching the CGM. Out of 42 patients, 36 patients (85.7%) were diagnosed with CAN (early CAN 57.1% and definite CAN 28.6%) and the mean TIR was 64.4% ±23.5%. Out of those with TIR <70%, 42.9% were affected with definite CAN compared to only 14.3% among those with TIR >70%. Patients with more severe CAN were found to have a lower TIR (P = 0.115). The study found a high prevalence of cardiac autonomic neuropathy (CAN) of around 85.7% in type 2 diabetes patients. Lower TIR values were associated with a higher incidence of definite CAN (42.9% vs. 14.3% in TIR <70% vs. >70% groups). The findings suggest TIR is inversely associated with the presence and severity of cardiac autonomic neuropathy in type 2 diabetic patients and also a potential link between TIR and CAN severity.

Prevalence of cardiac autonomic neuropathy in patients with type 2 diabetes mellitus.

Cardiac autonomic neuropathy (CAN) is one of the microvascular complications of diabetes mellitus, which is due to the involvement of autonomic nerve fibers innervating the heart and blood vessels. CAN was found to have a greater degree of morbidity and mortality than their non-CAN counterparts as it is underdiagnosed. Hence, this study aims to determine the prevalence and severity of CAN in type 2 diabetics in the South Indian setting. Forty-two patients with type 2 diabetes mellitus were enrolled in the study. Patients underwent tests for CAN, with the severity of CAN estimated as a CAN score, which was the sum of the scores of the four cardiovascular autonomic function tests. Out of the 42 patients, a total of 36 patients (85.7%) were diagnosed with CAN. Among those with CAN, 24 patients had early CAN (57.1%), and 12 were diagnosed with definite CAN (28.6%). Patients with any form of CAN (early and definite CAN) had higher HbA1c and mean glucose values than those without CAN. CAN was also found to be more severe among older patients with diabetes. In the present study, we found that more than 50% of the study population had early CAN and around 28.6% patients had definite CAN indicating higher prevalence of CAN in our population. Also, there was a positive correlation between the severity of CAN and the age of the patients. This study highlights the importance of understanding the importance of screening the diabetic patients for CAN to prevent adverse cardiovascular events.

The Composite Autonomic Symptom Score 31 Questionnaire: A Sensitive Test to Detect Risk for Autonomic Neuropathy.

Autonomic neuropathy is a common but often neglected complication of diabetes, prediabetes, and even in individuals with an elevated risk of diabetes. The Composite Autonomic Symptom Score (COMPASS) 31 is a validated and easy-to-use questionnaire regarding autonomic symptoms. We aimed to use a digitally, Norwegian version of the COMPASS 31 in people with different durations of diabetes and healthy controls to consider feasibility and to investigate if scores could discriminate between positive and negative outcomes for established tests for diabetic neuropathy, including cardiovascular autonomic neuropathy (CAN) and a novel method of examining the gastrointestinal visceral sensitivity. We included 21 participants with longstanding type 2 diabetes, 15 with early type 2 diabetes, and 30 matched controls. The mean age for all groups was 69 years. Participants were phenotyped by cardiovascular autonomic reflex tests, electrical skin conductance, sural nerve electrophysiology, and the monofilament test. As a proxy for gastrointestinal visceral and autonomic nerve function, evoked potentials were measured following rapid rectal balloon distention. Participants with longstanding diabetes scored a median (IQR) of 14.9 (10.8-28.7) points, early diabetes of 7.3 (1.6-15.2), and matched controls of 8.6 (4.1-21.6), p = 0.04. Women and men scored 14.4 (5.5-28.7) and 7.8 (3.6-14.6) points, respectively, p = 0.01. Participants with definite or borderline CAN scored 14.3 (10.4-31.9) points, compared to participants with no CAN, 8.3 (3.2-21.5), p = 0.04. Lowering the diagnostic cut-off from 16 to 10 points increased the sensitivity from 0.33 to 0.83, with a decreased specificity from 0.68 to 0.55. We successfully used COMPASS 31 in Norwegian. Thus, following the guidelines, we suggest clinical implementation for the assessment of autonomic neuropathy. Participants with longstanding diabetes had an increased likelihood of symptoms and signs of autonomic neuropathy. For screening purposes, the sensitivity was improved by lowering the cut-off to 10 points, with a lower score nearly excluding the diagnosis.

Diabetic cardiac autonomic neuropathy: insulin resistance, lipid profile, and omega-3 polyunsaturated fatty acids

The significance of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM) has been not fully appreciated and there is no unified treatment algorithm. Aim: The aim of study was to investigate the effects of -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) parameters in patients with T2DM and definite CAN. The study involved 33 patients with T2DM and definite CAN. Patients were allocated into two treatment groups: 1st group - 15 patients received standard hypoglycaemic therapy - control (n = 15); 2nd group (n = 18) - standard hypoglycaemic therapy and 1 capsule/day of the ω-3 PUFAs (1 g, including 90 % ω-3 PUFAs) for three months. The concentrations of glucose, glycated haemoglobin A1c, immunoreactive insulin in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The insulin resistance Homeostasis model assessment, atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG glucose (TyG) index were calculated. Obtained results of our study could witness that the prescription of -3 PUFAs was accompanied by a statistically significant decrease in TG concentration; AC, TG/LDL-C, TG/TC, TG/LDL-C, TyG index parameters and increase in HDL-C levels (compared to control). Conclusions. Obtained results justify the appropriateness of -3 PUFAs prescriptions to patients with T2DM and definite CAN.

DIABETIC CARDIAC AUTONOMIC NEUROPATHY: SIMVASTATIN, INSULIN RESISTANCE AND LIPIDS

Treatment of diabetic cardiac autonomic neuropathy (CAN) is a complex process, that includes: lifestyle modification; reducing of insulin resistance (IR); optimal glycemic control; management of diabetic dyslipidemia; antioxidants; vitamins; treatment of myocardial metabolic abnormalities; thrombosis and others. The aim of study was to investigate the effects of simvastatin on insulin resistance and blood lipid profile parameters in patients with type 2 diabetes mellitus (T2DM) and the definite stage of cardiac autonomic neuropathy. The study involved 107 patients with T2DM among them 16 patients without CAN, 19 with subclinical stage of CAN and 72 with definite CAN. Median age of patients was 53.6 ± 0.41 yrs, disease duration - 4.12 ± 0.24 yrs and median glycated hemoglobin (HbA1c) - 7.01% ± 0.09%. The control group included 14 almost healthy people without DM. Patients with definite CAN were allocated into two treatment groups: 1st group - 22 patients received standard hypoglycemic therapy and simvastatin 20 mg/day; 2nd group - control (n = 15). The duration of the study was 3 mos. The concentrations of glucose, HbA1c, immunoreactive insulin (IRI) in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The IR index (HOMA-IR), atherogenic coefficient (AC), TG/HDL-C parameters, and TG-glucose (TyG) index were calculated. It was established that in patients with T2DM with subclinical stage of CAN there was statistically significant increase in the parameters of HbA1c, IRI, TC, TG and HOMA-IR, AC, TyG indices and decrease of TG/HDL-C and HDL-C compared to control; increase of IRI, TG, TG/HDL-C and TyG indices compared to patients with T2DM without CAN. The definite stage of CAN is characterized by an increase of HbA1c, IRI, TC, LDL-C levels and HOMA-IR, AC indices and a significant decrease in the concentration of HDL-C (compared to patients with subclinical CAN). As a result of our study, we found out that prescription of simvastatin to patients with definite stage of CAN was accompanied by a statistically significant decrease in the concentration of TC, LDL-C, TG and an increase in the content of HDL-C (compared to 2nd, control group). Obtained results justify the appropriateness of statins prescription to patients with T2DM and the definite stage of CAN.

A Study of Cardiovascular Autonomic Neuropathy in Adult Patients with Diabetes Mellitus at Levy Mwanawasa University Teaching Hospital

Cardiac autonomic neuropathy (CAN) is the diminished capacity of autonomic regulation of the cardiovascular system occurring in the presence of diabetes mellitus (DM) and in the absence of other aetiologies. Diabetes mellitus is a well- known cause of peripheral neuropathy. However, in comparison to somatic neuropathy, autonomic neuropathy is an under-diagnosed and under-treated chronic complication of diabetes mellitus despite its serious and significant contribution to morbidity and mortality in the diabetes mellitus population. A variety of tests, based on evaluation of the cardiovascular reflexes triggered by performing specific provocative manoeuvres, have been proposed to measure autonomic function. This study used four cardiovascular reflex tests to estimate appropriate autonomic function by examining heart rate, heart rate variation and the baroreceptor reflex. The aim of this study was to determine the presence of cardiovascular autonomic neuropathy in adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital in Lusaka, Zambia. Adult patients with diabetes mellitus, aged between 21 and 70 years, participated in this cross-sectional study. Four, non-invasive, cardiac autonomic reflex tests to assess for cardiac autonomic neuropathy were employed according to Ewing’s method. The parasympathetic function was analysed based on the heart rate response to paced deep breathing and to Valsalva manoeuvring. The sympathetic function was assessed by measuring heart rate and blood pressure response to postural change. Ewing`s criteria was used for the categorisation of cardiac autonomic neuropathy. Data were analysed using SPSS version 20. Continuous data were presented as means and standard deviation. Categorical data were analysed using a Fishers’ Exact Test (χ2) and a logistic regression was performed to verify the effects of diabetes mellitus’ duration, sex and age on the probability that the participants have cardiac autonomic neuropathy. A total of 52 patients participated in the study. The prevalence of Cardiac autonomic neuropathy was 48.1%. Out of 52 patients, 42.3% had definite cardiac autonomic neuropathy and 5.8% had severe cardiac autonomic neuropathy. Early cardiac autonomic neuropathy was observed in 34.6% of patients while 17.3% had no signs of cardiac autonomic neuropathy. The mean age of patients with cardiac autonomic neuropathy was 54.44 ± 10.90 years and the mean duration of diabetes mellitus from diagnosis was 5.36 ± 6.78 years. The probability of developing cardiac autonomic neuropathy increased with increasing age and hypertensive participants were more likely develop cardiac autonomic neuropathy (ѵ = 5.82, p = .001). In conclusion, cardiac autonomic neuropathy was present in a significant proportion of adult patients with diabetes mellitus at Levy Mwanawasa University Teaching Hospital, reflecting the increased morbidity encountered by this population. In order to improve patient quality of life and reduce disease burden, screening for cardiac autonomic neuropathy should be implemented using cardiovascular autonomic reflex tests which are relatively simple, safe and affordable.

Relationship between vitamin D status and cardiac autonomic neuropathy in prediabetes.

Studies have suggested that vitamin D deficiency is associated with impaired cardiac autonomic nerve function. This study explores the correlation between serum vitamin D and cardiac autonomic neuropathy (CAN) in prediabetes and reveals the protective effect of vitamin D against CAN. In total, 113 patients with prediabetes and definite CAN and 180 with prediabetes but without CAN were enrolled on the basis of their standard cardiovascular autonomic reflex test results. Chemiluminescence was used to measure 25(OH)D, the patients with CAN were divided into four groups, and the heart rate variability (HRV) of the study groups were compared. Relative to the 50≤25(OH)D<75-nmol/L group, the 25≤25(OH)D<50-nmol/L and 25(OH)D<25-nmol/L groups exhibited significant differences in the time and frequency domains of HRV (p< 0.05). Furthermore, we discovered that 25(OH)D is positively correlated with standard deviation of normal-to-normal RR intervals (SDNN) (β=0.566, p<0.05) and negatively correlated with low-to-high frequency ratio (LF/HF) (β=-0.199, p<0.05). A logistic regression reveals that CAN in prediabetes is significantly correlated with the 25(OH)D concentrations of <25 nmol/L (OR, 2.380 [1.208-4.691]; p<0.05) and 25≤25(OH)D<50 nmol/L (OR, 1.875 [1.064-3.751]; p<0.05). Serum 25(OH)D is significantly correlated with CAN in prediabetes, especially in the 25(OH)D <25-nmol/L group. Therefore, vitamin D deficiency may be related to the occurrence of CAN in prediabetes, and appropriate supplementation may provide protection against CAN.

Diabetic Cardiovascular Autonomic Neuropathy: Effects of Simvastatin and Omega-3 Polyunsaturated Fatty Acids on Insulin Resistance and Lipid Profile Parameters

Introduction. Currently, there is no unified treatment algorithm of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to investigate the effects of simvastatin (SIM) and -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) in patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Materials and methods. The study involved 72 patients with T2DM and definite CAN. Patients were divided into four groups: 1st - received standard hypoglycemic therapy - control (n = 15); 2nd (n = 22) – in addition simvastatin (SIM) 20.0 mg/q.d.; 3rd (n = 18) - in addition 1 capsule/q.d. of the ω-3 PUFAs; 4th (n = 17) - in addition SIM 10.0 mg/q.d and 1 capsule/q.d of the ω-3 PUFAs for three months. The concentration of glucose, glycated hemoglobin A1c, immunoreactive insulin (IRI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) in the blood were determined. Homeostasis model assessment IR (HOMA-IR), atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG and glucose index (TyG) were calculated. Results. Prescription of SIM was accompanied by a statistically significant decrease in TC, LDL-C, TG concentrations. In parallel, SIM induced a decrease of AC, TG/HDL-C, increase in HDL-C, and does not affect the IRI, HOMA-IR, TG/LDL-C, TG/TC, TC/LDL-C/HDL-C, TyG. The use of ω-3 PUFAs has contributed to a significant reduction in TG, AC, TG/LDL-C, TG/TC, TG/HDL-C, TyG index, increase in HDL-C, and was not accompanied by changes in IRI content, HOMA-IR, TC, LDL-C, and TC/LDL-C/HDL-C. The combined prescription of SIM and -3 PUFAs was accompanied by more pronounced, statistically significant changes in the blood lipid spectrum, as well as a decrease in the IRI and HOMA-IR. Conclusions. Obtained results justify the appropriateness of combined simvastatin and -3 polyunsaturated fatty acids prescription to patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Keywords: diabetes mellitus, cardiac autonomic neuropathy, treatment.

Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy.

Objective. Significantly underdiagnosed, diabetes-associated cardiac autonomic neuropathy (CAN) causes a wide range of cardiac disorders that may cause life-threatening outcomes. This study investigated the effects of alpha-lipoic acid (ALA) on arterial stiffness and insulin resistance (IR) parameters in type 2 diabetes mellitus (T2D) patients and definite CAN. Methods. A total of 36 patients with T2D and a definite stage of CAN were recruited. This investigation was carried out on two separate arms: traditional hypoglycemic therapy (n=18, control) and ALA (n=18) 600 mg in film-coated tablets/q.d. in addition to traditional hypoglycemic therapy. The duration of the study was three months. Results. In subjects with T2D and definite stage of СAN, treatment with ALA resulted in a significant decrease of glucose, immunoreactive insulin concentration, and Homeostasis Model Assessment (HOMA)-IR (HOMA-IR) parameters; pulse wave velocity (PWV), aorta augmentation index (AIxao) during the active period of the day and decrease of PWV, AIxao, and brachial augmentation index during the passive period of the day compared with the results, obtained in the control group. Therefore, the administration of ALA to patients with T2D for three months promotes the improvement of glucose metabolism and arterial stiffness parameters. Conclusions. In patients with T2D and definite stage of СAN treatment with ALA improved HOMA-IR and arterial stiffness parameters. These findings can be of clinical significance for the complex treatment of diabetes-associated CAN.

Reliability of heart-rate-variability features derived from ultra-short ECG recordings and their validity in the assessment of cardiac autonomic neuropathy

ObjectiveOur research aimed at providing methodologically strong evidence for the reliability of HRV analysis of ultra-short (10–150 s) ECGs compared to the benchmark of 300 s. Furthermore, we evaluated the retainment of HRV differences between participants with definite cardiac autonomic neuropathy (dCAN) and controls as ECG recording length was reduced to 10 s. MethodsPre-processed ECG recordings from 11 individuals with dCAN and 76 healthy controls were used to determine SDNN, RMSSD, Low Frequency (LF) and High Frequency (HF) and assess whether the reliability of HRV features remains comparable for ultra-short ECG time series. For frequency domain analysis, the Lomb-Scargle-Periodogram (LSP) and Fast-Fourier-Transform (FFT) approaches were compared. Nonparametric areas under the curve (AUCs) were estimated to examine the overall ability of ultra-short HRV to classify dCAN from ECGs of 10–300 s. ResultsRMSSD and HF were reliable and retained significant differences between control and dCAN from ECGs down to 10 s. SDNN and LF could be considered reliable in recordings of at least 30 s. LSP and FFT yielded comparable results. Most prevalent group differences were found for LF between 60 and 300 s. ConclusionRMSSD and HF were reliable HRV features showing excellent potential for the classification of dCAN from 10-s ECG strips. For recordings longer than one minute, LF proved to be reliable and yielded best discrimination results. SignificanceThe current research indicated that ultra-short HRV analysis has the potential to become a time-efficient and accurate diagnostic tool for dCAN in clinical practice.

Association of serum CTRP9 levels with cardiac autonomic neuropathy in patients with type 2 diabetes mellitus.

AimsCardiac autonomic neuropathy (CAN) is a serious complication of diabetes and is associated with adipokines. The C1q tumor necrosis factor‐related protein 9 (CTRP9) is a newly discovered adipokine. This study aimed to evaluate the association of serum CTRP9 levels with the prevalence and severity of CAN in patients with type 2 diabetes mellitus.Materials and MethodsWe enrolled 262 patients (aged ≥18 years) with type 2 diabetes mellitus into this study. Standard cardiovascular autonomic reflex tests (CARTs) were used to assess CAN and patients were divided into three groups accordingly: a non‐CAN group, an early CAN group, and a definite CAN group. Serum CTRP9 levels were measured by enzyme‐linked immunosorbent assay, and the tertiles were calculated.ResultsSerum CTRP9 levels decreased significantly in the early CAN and definite CAN groups (P < 0.05). The percentage of definite CAN was the highest at the minimum tertile of serum CTRP9 level (T1; P < 0.05). Additionally, serum CTRP9 levels were negatively correlated with age, DM duration, hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) while positively correlated with high‐density lipoprotein cholesterol (HDL; P < 0.05). The level of CTRP9 was also significantly associated with the four indexes of CARTs (P < 0.05). Furthermore, CTRP9 was a protective factor for definite CAN (P < 0.05). Compared with the maximum tertile (T3) of the serum CTRP9 levels, a decreased level of serum CTRP9 in T1 significantly increased the prevalence ratio of definite CAN in patients with type 2 diabetes mellitus (P < 0.05).ConclusionSerum CTRP9 levels were independently associated with definite CAN. CTRP9 represents a reliable biomarker for exploring CAN in patients with type 2 diabetes mellitus.

Glycemic Variability and Diabetic Neuropathy in Young Adults With Type 1 Diabetes.

Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes.Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE).Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models.Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.

Diabetic Cardiovascular Autonomic Neuropathy: Insulin Resistance, Lipids and Simvastatin

Background: Treatment of diabetic cardiac autonomic neuropathy (CAN) is a complex process, that includes: lifestyle modification; reducing of insulin resistance (IR); optimal glycemic control; management of diabetic dyslipidemia; antioxidants; vitamins; treatment of myocardial metabolic abnormalities; thrombosis and others. The aim of study was to investigate the effects of simvastatin on insulin resistance and blood lipid profile parameters in patients with type 2 diabetes mellitus (DM) and the definite stage of cardiac autonomic neuropathy. Methods: The study involved 107 patients with type 2 DM among them 16 patients without CAN, 19 with subclinical stage of CAN and 72 with definite CAN. Median age of patients was 53.6±0.41 years, disease duration - 4.12±0.24 years and median glycated hemoglobin (HbA1c) - 7.01%±0.09%. The control group included 14 almost healthy people without DM. Patients with definite CAN were allocated into two treatment groups: 1st group - 22 patients received standard hypoglycemic therapy and simvastatin 20 mg/day; 2nd group - control (n = 15). The duration of the study was 3 mos. The concentrations of glucose, HbA1c, immunoreactive insulin (IRI) in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The IR index (HOMA-IR), atherogenic coefficient (AC), TG/HDL-C parameters, and TG-glucose (TyG) index were calculated. Result: It was established that in patients with type 2 DM with subclinical stage of CAN there was statistically significant increase in the parameters of HbA1c, IRI, TC, TG and HOMA-IR, AC, TyG indices and decrease of TG/HDL-C and HDL-C compared to control; increase of IRI, TG, TG/HDL-C and TyG indices compared to patients with type 2 DM without CAN. The definite stage of CAN is characterized by an increase of HbA1c, IRI, TC, LDL-C levels and HOMA-IR, AC indices and a significant decrease in the concentration of HDL-C (compared to patients with subclinical CAN). As a result of our study, we found out that prescription of simvastatin to patients with definite stage of CAN was accompanied by a statistically significant decrease in the concentration of TC, LDL-C, TG and an increase in the content of HDL-C (compared to 2nd, control group). Conclusion: Obtained results justify the appropriateness of statins prescription to patients with type 2 DM and the definite stage of CAN.

Prevalence and Correlates of Cardiovascular Autonomic Neuropathy Among Patients with Diabetes in Uganda: A Hospital-Based Cross-sectional Study

Background:Cardiovascular autonomic neuropathy (CAN) is a common complication in individuals with diabetes mellitus (DM) but often overlooked in clinical practice. The burden and correlates of CAN have not been extensively studied in low-income countries, particularly in sub-Saharan Africa.Objectives:To determine the prevalence and correlates of CAN among adults in ambulatory diabetes care in southwestern Uganda.Method:We conducted a cross-sectional study among adults with diabetes from November 2018 to April 2019. CAN was assessed using the five autonomic function tests: deep breathing, Valsalva maneuver, postural index on standing, change in blood pressure during standing and diastolic blood pressure response to isometric exercise. We estimated the prevalence of CAN and fit regression models to identify its demographic and clinical correlates.Results:We enrolled 299 individuals. The mean age was 50.1 years (SD ± 9.8), mean HbA1c was 9.7 (SD ± 2.6) and 69.6% were female. CAN was detected in 156/299 (52.2%) of the participants on the basis of one or more abnormal cardiovascular autonomic reflex tests. Out of 299 participants, 88 (29.4%) were classified as early CAN while 61/299 (20.4%) and 7/299 (2.3%) were classified as definite and severe (advanced) CAN respectively. In multivariable regression models, age over 50 years (aOR 3.48, 95%CI 1.35 –8.99, p = 0.010), duration of diabetes over 10 years (aOR 4.09, 95%CI 1.78 –9.38, p = 0.001), and presence of diabetic retinopathy (aOR 2.25, 95%CI 1.16 –4.34, p = 0.016) were correlated with CAN.Conclusions:Our findings reveal a high prevalence of CAN among individuals in routine outpatient care for diabetes mellitus in Uganda. Older age, longer duration of diabetes and coexistence of retinopathy are associated with CAN. Future work should explore the clinical significance and long term outcomes associated with CAN in this region.

Time in Range, as a Novel Metric of Glycemic Control, Is Reversely Associated with Presence of Diabetic Cardiovascular Autonomic Neuropathy Independent of HbA1c in Chinese Type 2 Diabetes.

Objective The objective of this study is to investigate the relationship between time in range (TIR), a new metric of continuous glucose monitoring (CGM) and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (T2DM). Methods A total of 349 individuals with T2DM were enrolled in this study. Evaluating by the standard cardiac autonomic reflex tests (CARTs), there were 228 diabetic individuals without cardiovascular autonomic neuropathy (without confirmed CAN) including absent CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (n = 83 cases) and early CAN (Results The total presence of CAN was 34.67% (definite CAN 31.23% and severe CAN 3.44%). Patients with more severe CAN had lower TIR (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (P < 0.001). With increasing quartiles of TIR, the presence of CAN by severity declined (Conclusion TIR is associated with the presence of CAN independent of HbA1c and GV metrics in Chinese type 2 diabetes.

Cardiovascular autonomic neuropathy as a cause of fatigue in chronic hypoparathyroidism.

Hypoparathyroidism (hypoPT) results in an impairment of quality of life (QoL), an increase in fatigue and a higher risk of mortality. Cardiovascular autonomic neuropathy (CAN) is an impairment of the cardiovascular autonomic system and is associated with increased mortality and fatigability. Patients with hypoPT show an increased risk of CAN. However, no previous studies have investigated the association between CAN and QoL in hypoPT. To test whether CAN is associated with fatigue and impaired QOL in hypoPT patients. We enrolled 48 subjects with postsurgical hypoPT treated with calcium and calcitriol and 38 healthy subjects who underwent thyroidectomy. Subjects completed the RAND 36-Item Short Form (SF-36) Health Survey, evaluating physical (PCS) and mental (MCS) health, and fatigue score. CAN was assessed using cardiovascular autonomic reflex tests (CARTs). Participants were considered to have "early CAN" (EC) if they had one abnormal CART and "definite CAN" (DC) with two or more abnormal CARTs. Compared with controls, hypoPT population had lower fatigue scores (44.5 IQRː9 vs 38.5 IQRː12.3, P = 0.031). In the hypoPT group, only participants with DC had a lower fatigue score than subjects without CAN (DC: β: -9.55, P = 0.005) after adjusting for age, duration of disease, calcium concentration, TSH, calcitriol and calcium supplementation. No differences were found in the PCS and MCS scores in the hypoPT group. CAN may explain fatigue, a common complaint of postsurgical hypoPT patients. Further larger and prospective investigations are needed to confirm our findings.

Diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) in early detection of autonomic dysfunction in type 2 diabetes mellitus.

PurposeDiabetic autonomic neuropathy (DAN) is a common and disabling complication of diabetes, with cardiac autonomic neuropathy (CAN) being a major cause of mortality and morbidity. Standard autonomic function tests (AFT) are cumbersome and time consuming to conduct in OPD setting.ObjectiveTo evaluate the diagnostic accuracy of composite autonomic symptom scale 31 (COMPASS-31) as a screening test for DAN.Patients and methodsA cross-sectional study which enrolled 60 type 2 diabetes individuals was conducted at a tertiary care center. Autonomic functions were evaluated by COMPASS-31 questionnaire as well as by standard Ewing's battery of tests; short-term heart rate variability; sympathetic skin response along with nerve conduction studies.ResultsThirty males and 24 females completed the study. Forty-nine (89%) participants had CAN, of which, 9 (17%) had definite CAN. Peripheral neuropathy was present in 20 (37%). COMPASS-31 scores showed no difference between “No CAN” and “Early CAN”. “Definite CAN” individuals differed significantly from “No and Early CAN” on COMPASS-31 scores and its gastrointestinal sub-domain. Receiver operating characteristic between “Definite CAN” and “No and Early CAN” showed fair accuracy with AUC of 0.731 (95% CI 0.561–0.901), sensitivity 77.8%, specificity 71.7% at a cut-off of 28.67 of COMPASS-31 score. Gastrointestinal sub-domain, at a cut-off score of 5.8, had 77.8% sensitivity, 60% specificity, and AUC was 0.748 (95% CI 0.603–0.894).ConclusionCOMPASS-31, a self-administered tool, requiring less time, qualifies as an acceptable screening tool, especially for definite CAN. However, individuals scoring low on COMPASS-31 are still required to be evaluated by Ewing’s battery to differentiate between “Early CAN” and “No CAN”.

Investigation of Linear and Nonlinear Properties of a Heartbeat Time Series Using Multiscale Rényi Entropy.

The time series of interbeat intervals of the heart reveals much information about disease and disease progression. An area of intense research has been associated with cardiac autonomic neuropathy (CAN). In this work we have investigated the value of additional information derived from the magnitude, sign and acceleration of the RR intervals. When quantified using an entropy measure, these time series show statistically significant differences between disease classes of Normal, Early CAN and Definite CAN. In addition, pathophysiological characteristics of heartbeat dynamics provide information not only on the change in the system using the first difference but also the magnitude and direction of the change measured by the second difference (acceleration) with respect to sequence length. These additional measures provide disease categories to be discriminated and could prove useful for non-invasive diagnosis and understanding changes in heart rhythm associated with CAN.