Early Cardiac Autonomic Neuropathy Research Articles

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.

Cardiac Autonomic Neuropathy in Newly Diagnosed Patients With Type 2 Diabetes Mellitus.

Cardiac autonomic neuropathy (CAN) is a debilitating complication in diabetes mellitus, leading to life-threatening arrhythmias and various impairments. Its prevalence varies widely, and early detection and management are crucial. This study investigates the prevalence of CAN in newly diagnosed type 2 diabetes mellitus patients in Central India, comparing them to a control group. This case-control study included 35 newly diagnosed type 2 diabetes mellitus patients and 35 age-matched healthy controls from the general population. Cardiac autonomic function testing (AFT) was done by heart rate variability (HRV), the deep breathing test (DBT), the cold pressor test (CPT), and the lying-to-standing test (LST). Parameters were recorded and analyzed usingstatistical tests. Patients with type 2 diabetes mellitus had significantly higher weight, BMI, fasting blood sugar, post-prandial blood sugar, urine albumin-creatinine ratios, and systolic and diastolic blood pressure than controls. Abnormalities in HRV and E: I ratio during the DBT and CPT were more prevalent in these patients. Parasympathetic dysfunction (delta HR) and a lower E: I ratio were also significantly highin this group. Also, LST results suggested a greater likelihood of orthostatic symptoms in the patients' group. This study highlights the importance of AFT in diagnosing early CAN in newly diagnosedpatients. Early diagnosis and management of diabetic CAN are essential to prevent complications.

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 association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes

Background and aimInsulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D. DesignA cross-sectional study. MethodsA total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR). ResultsThe population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24−43), median disease duration of 14 years ( ± 9.5–21.5), a median BMI value of 23.7 kg/m2 (21.4–26.6), an HbA1C of 7.2% (6.7–8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2–9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06–6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02–9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94–12.79, p = 0.001). No association was shown with ACR. ConclusionsIn patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.

Cardiac Autonomic Nerve Dysfunction Predicts Incident Retinopathy and Early Kidney Dysfunction in Adolescents With Type 1 Diabetes.

Cardiac autonomic neuropathy (CAN) may contribute to vascular complications in diabetes. We hypothesized that adolescents with CAN are at greater risk of diabetic retinopathy and early kidney dysfunction. In this prospective longitudinal study of 725 adolescents with type 1 diabetes without retinopathy and albuminuria at baseline, early CAN was defined as one or more abnormalities in seven heart rate tests derived from a 10-min electrocardiogram. Retinopathy was defined as the presence of one or more microaneurysms, early kidney dysfunction as an albumin excretion rate (AER) >7.5 μg/min, and albuminuria as an AER >20 μg/min. Multivariable generalized estimating equations were used to examine the association between CAN and retinopathy or early kidney dysfunction. Cox proportional hazards regression analysis was used to assess cumulative risks of incident retinopathy and albuminuria. At baseline, the mean age of the sample was 13.6 ± 2.6 years, 52% were male, and mean diabetes duration was 6.1 ± 3.3 years. Over a median follow-up of 3.8 (interquartile range 2.2-7.5) years, the complication rate 27% for retinopathy, 16% for early kidney dysfunction, and 3% for albuminuria. The mean study HbA1c was 72.3 ± 16 mmol/mmol (8.6 ± 1.4%). CAN predicted incident retinopathy (odds ratio 2.0 [95% CI 1.4, 2.9]) and early kidney dysfunction (1.4 [1.0, 2.0]) after adjusting for HbA1c and diabetes duration. CAN also predicted retinopathy (hazard ratio 1.57 [95% CI 1.09, 2.26]) and albuminuria (2.30 [1.05, 5.04]) independently of HbA1c. CAN predicted incident retinopathy and kidney dysfunction in adolescents with type 1 diabetes, likely reflecting autonomic microvascular dysregulation contributing to complications. Therefore, screening and interventions to reduce CAN may influence the risk of complications.

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.

Prediction of cardiac autonomic neuropathy using a machine learning model in patients with diabetes.

Background:Cardiac autonomic neuropathy (CAN) is a diabetes-related complication with increasing prevalence and remains challenging to detect in clinical settings. Machine learning (ML) approaches have the potential to predict CAN using clinical data. In this study, we aimed to develop and evaluate the performance of an ML model to predict early CAN occurrence in patients with diabetes.Methods:We used the diabetes complications screening research initiative data set containing 200 CAN-related tests on more than 2000 participants with type 2 diabetes in Australia. Data were collected on peripheral nerve functions, Ewing’s tests, blood biochemistry, demographics, and medical history. The ML model was validated using 10-fold cross-validation, of which 90% were used in training the model and the remaining 10% was used in evaluating the performance of the model. Predictive accuracy was assessed by area under the receiver operating curve, and sensitivity, specificity, positive predictive value, and negative predictive value.Results:Of the 237 patients included, 105 were diagnosed with an early stage of CAN while the remaining 132 were healthy. The ML model showed outstanding performance for CAN prediction with receiver operating characteristic curve of 0.962 [95% confidence interval (CI) = 0.939–0.984], 87.34% accuracy, and 87.12% sensitivity. There was a significant and positive association between the ML model and CAN occurrence (p < 0.001).Conclusion:Our ML model has the potential to detect CAN at an early stage using Ewing’s tests. This model might be useful for healthcare providers for predicting the occurrence of CAN in patients with diabetes, monitoring the progression, and providing timely intervention.

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.

548-P: Early Liver Dysfunction Predicts Cardiac Autonomic Neuropathy in Adolescents with Type 1 Diabetes

Background: With increasing incidence of obesity, metabolic syndrome is not uncommon in type 1 diabetes (T1D). The association of liver dysfunction and cardiovascular disease is well established in type 2 diabetes but not in T1D. We aim to investigate associations between liver dysfunction and diabetic retinopathy and cardiac autonomic neuropathy (CAN) in adolescents with T1D. Methods: A longitudinal study of 102 adolescents with T1D with repeated measures of liver function and CAN over 3 years. CAN was defined as 2 or more abnormal heart rate variability measures derived from a 10 minute ECG recording using Labchart Pro (mean HR; Standard deviation of mean NN intervals; root mean squared difference of successive NN intervals; low/high frequency ratio; geometric measure- Triangular index). Generalized estimating equations were used to explore associations between tertiles of liver function enzymes and cardiac autonomic neuropathy and retinopathy after adjusting for known risk factors. Results: Baseline mean + age was 14.6 + 1.9yrs, HbA1C 8.2 + 1.4 and median duration 7.2yrs (IQR 4.8-9.6), mean BMI 23 + 4.1. Higher ALT was associated with CAN (Table1) but not retinopathy. Conclusion: Higher ALT was associated with early CAN in youth with T1D. Inflammation might lead to higher ALT. Further studies into the potential role for obesity, liver dysfunction and CAN are required. Disclosure V. Velayutham: None. P.Z. Benitez-Aguirre: None. M.E. Craig: None. J. Cusumano: None. G. Liew: None. K.C. Donaghue: None.

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”.

DIAGNOSIS OF THE CARDIAC AUTONOMIC NEUROPATHY IN DIABETIC PATIENT

Cardiac autonomic neuropathy (CAN) is a very common diabetes-related complication that has a major effect on CVD, mortality and morbidity in patients with DM. Careful and timely testing of CAN with easy standard bedside tests in patients with DM 1 and 2 is critically important for early diagnoses and prophylaxes of further CV complications. Aim of the study was to evaluate the CAN characteristics in DM 1 versus DM 2 patients and to identify the relationship between CAN and typical diabetic complications. Materials and methods. A descriptive and comparative cross-sectional study was developed with 75 patients with Diabetes Mellitus (DM 1 — 30 patients, DM 2 — 45 patients) who were hospitalized to the endocrinology department for treatment. All patients were investigated routinely – complains, anamnestic data, objective examination, lab and instrumental examination. For defining of CAN next five classical tests were done (cardiac autonomic reflex testing (CART)): Evaluating of the Resting tachycardia; Heart rate response to deep breathing; Valsalva maneuver; Systolic blood pressure response to standing; Diastolic blood pressure response to sustained handgrip. Results and discussions. Absence of CAN, according to proposed score, was defined in those patients without clinical features of CVD. 46.8% of all patients presented with early and definitive CAN, while the higher prevalence of definitive CAN was diagnosed in DM 2 patients. Severe CAN was confirmed more often in DM 2 patients also. Coexistence of CAN and peripheral neuropathy was higher in patients with DM 1 than in DM 2 patients. Among DM 1 patients with CAN only 11.8% persons had not sensory peripheral neuropathy, while 29.7% DM 2 patients with CAN, were free of sensory peripheral neuropathy. Positive correlations were found between the duration of the DM and manifestations of CAN in patients with DM II, the development of sensory polyneuropathy, retinopathy and CAN in patients with DM I, and this diabetic complication preceded the clinical manifestations of peripheral neuropathy. Thus, the proposed set of diagnostic measures should be obviously and easily used for the timely diagnosis of CAN in diabetic patients, especially in asymptomatic cases, and objectively assessing the effectiveness of the therapy.

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.

Early diagnosis of diabetic cardiac autonomic neuropathy by method of high-frequency ultrasonic dopplerography

Introduction. Diabetic neuropathy is the most wide-spread complication of diabetes mellitus and neuropathy is steadily progressing even with compensation of the underlying disease. The search of the new methods of treatment and diagnosis of neuropathy is required. Diabetic autonomic neuropathy lies in the base of early morbidity and mortality of diabetic patients.We estimated the potential of High-frequency Ultrasonic Dopplerography for diagnosis of autonomic neuropathy. Material and methods. 26 diabetic patients with sensorimotor neuropathy were examined. Microvascular blood flow of finger skin was assessed at rest as well as in functional tests: with cold impact and occlusion (cuff). Cardiac autonomic neuropathy was assessed using several cardiovascular autonomic reflex tests as a gold standard of diagnosis. Diagnostic values of microvascular blood flow test in detecting of cardiac autonomic neuropathy staging were evaluated in comparing with traditional modalities.Results. Cardiac autonomic neuropathy was found for all patients and definite/confirmed staging in 61.5 % cases. Initial parameters of microvascular blood flow velocity were significantly decreased in all patients in comparing with control (Vam= = (1.9±0.22); (1.7±0.51) and (6.7±0.51) sm/s in patients with early cardiac autonomic neuropathy, definite/confirmed staging and control subjects respectively, p&lt;0.05). Microvascular blood flow functional testes had great informational content for diagnosis of autonomic neuropathy (sensitivity – 100 and 58 %, specify – 50 and 80 % respectively). The algorithm of diabetic patients examination was offered for early diagnosis of autonomic neuropathy staging.Conclusions. High-frequency Ultrasonic Dopplerography allowed to separate of cardiac autonomic neuropathy stages. This study is necessary to continue for revealing of all method possibilities.

573-P: Diagnostic Performance of Heart Rate Variability for Detecting Diabetic Cardiac Autonomic Neuropathy

Heart rate variability (HRV) has been considered as a useful tool for detecting cardiac autonomic neuropathy (CAN) and predicting mortality in individuals with diabetes. We evaluated its diagnostic performance for CAN in a hospital-based cohort. CAN was defined and classified according to Ewing’s criteria using standard 5 cardiovascular reflex test. HRV and power spectral density (PSD) were assessed by DiCAN (Medicore, Seoul, Korea); and diagnostic performance of Standard Deviation Normal to Normal (SDNN) and each PSD domain (total power, TP; very low frequency, VLF; low frequency, LF; high frequency, HF) were evaluated using receiver operating characteristic (ROC) analysis and Youden's index. After excluding subjects with insufficient data, 2,209 diabetic patients were included the analyses (mean age, 60 ± 11 years; men, 49.6%). Early, definite, and severe CAN were detected in 38.7%, 10.4%, and 4.1% in them. Multivariable Poisson regression adjusted for age and sex showed that all SDNN, TP, VLF, LF, and HF were decreased as severity of CAN increased (P&amp;lt;0.001). Their area under curve of ROC for diagnosis of definite CAN was 0.67 (95% confidence interval, 0.64 - 0.70), 0.71 (0.68 - 0.74), 0.68 (0.65 - 0.71), 0.73 (0.70 - 0.75), and 0.68 (0.65 - 0.71), respectively; and their sensitivity was 0.74, 0.80, 0.70, 0.70, and 0.79, respectively in this analysis. For detection of early CAN, their sensitivity was more decreased to 0.71, 0.64, 0.52, 0.64, and 0.74, respectively. In conclusion, even though there was significant decrease in HRV according to severity of CAN, HRV could not detect about 30% of diabetic subjects with CAN especially in the case with early impairment. Further studies evaluating diagnostic performance of HRV in various populations are needed. Disclosure B. Koo: None. M. Moon: None.

Progressive Hemodynamic and Cardiac Autonomic Impairment as a Function of Metabolic State: Local Adipose vs. Systemic Inflammation

Cardiac autonomic neuropathy (CAN) commonly occurs early in the course of diabetes with significant cardiovascular mortality and morbidity. CAN development is linked to hyperglycemia; however, current understanding extends cardiovascular risk to pre‐diabetic patients without glycemic changes. Recent evidence suggests that anti‐diabetic drugs reduce the risk of cardiovascular complications in pre‐diabetes. The mechanism leading to early CAN development, its temporal evolution from pre‐diabetes to diabetes, and the response to therapeutic interventions were not previously described. To address these questions, we developed a rat model of mildly increased caloric intake (HC‐rat) with delayed development of hyperglycemia. Twelve weeks of feeding were not associated with an increase in neither body weight, blood pressure, nor blood glucose levels. These rats only showed an elevated serum insulin level indicative of insulin resistance. Type 2 diabetes was induced by the injection of low‐dose streptozotocin (STZ, 40 mg/kg). Echocadiography and invasive hemodynamic recording were used to assess cardiac autonomic function. Western blotting, PCR, and immunohistochemistry were employed to investigate different changes on the structural and molecular levels. Pre‐diabetic rats showed localized perivascular adipose inflammation together with parasympathetic dysfunction (suppression of baroreflex sensitivity in response to vasopressors), with no signs of cardiac structural or functional impairment. These abnormalities were reversed by non‐hypoglycemic doses of Metformin (Met, 100 mg/Kg) and Pioglitazone (Pio, 2.5 mg/Kg). On the other hand, rats with overt hyperglycemia developed systemic inflammation, with increased IL‐1b levels in serum, brainstem, and heart apex. Augmentation of inflammation in diabetic rats was associated with worsening cardiac autonomic function extending to sympathetic function (suppression of baroreflex sensitivity in response to vasodilators). While control of hyperglycemia through insulin treatment reversed the sympathetic deficit, parasympathetic function was only restored by combined treatment with Insulin+Met or Insulin+Pio producing the highest decrease in systemic inflammation in diabetic rats. As well, diabetic rats showed signs of focal ischemia in ventricular tissues together with an impaired systolic function apparent as &gt;50% decrease in maximal rate of rise of left ventricular pressure. Our present results outline a framework for sequential involvement of disparate detrimental mechanisms in the course of metabolic disease leading to a differential impact on cardiac autonomic control. Furthermore, our findings emphasize the value of early intervention with antidiabetic drugs with potential pleotropic effects.Support or Funding InformationSupported by AUB‐FM MPP grant # 320148This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Study of Cardiac Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus: A Northeast India Experience.

Aim:To investigate the prevalence and the risk factors for cardiac autonomic neuropathy (CAN) in type 2 diabetes mellitus (DM) patients.Study Design:Cross-sectional cohort study.Place and Duration of Study:This study was conducted in the Department of Endocrinology, Gauhati Medical College and Hospital, Assam, India between December 2016 to March 2018.Methodology:We included 100 patients (60 males and 40 females; age range: 36–72 years) with type 2 DM. Their clinical, biochemical, and metabolic parameters were analyzed and assessment of CAN were done based on the Ewing's criteria.Results:Out of 100 patients, 60 were males and 40 were females. The mean age of the patients was 53.3 ± 10.37 years (36–72 years) and the mean duration of diabetes was 9.03 ± 6.4 years (6 months–25 years). Patients were divided into two groups: “without CAN” (CAN−) and “with CAN” (CAN+). The prevalence of CAN was 70%, with early CAN in 25%, definite CAN in 24%, and severe CAN in 21% cases The patients with CAN were older (P = 0.0005), had longer diabetes duration (11.56 vs. 3.13; P = 0.0001), higher creatinine (P < 0.0001), and lower estimated glomerular filtration rate (eGFR) (P = 0.0001) compared to patients without CAN. Retinopathy, peripheral neuropathy, and nephropathy were common in CAN + patients. On multiple logistic regression analysis, duration of diabetes [odds ratio (OR); 6.7, P < 0.0001), older age (OR; 1.07, P < 0.016), and lower eGFR (OR; 0.97, P < 0.03) were risk factors for CAN.Conclusion:CAN is a common microvascular complication in type 2 DM with duration of diabetes, age, and severity of nephropathy being its significant determinants.

Study Of Cardiac Autonomic Neuropathy In Type 2 Diabetes Mellitus

Background: Cardiac Autonomic Neuropathy (CAN) represents a significant cause of morbidity and mortality in diabetic patients and is associated with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. Cardiac autonomic function should be assessed in most dia-betic patients as it contributes to the evaluation of cardiovascular risk. The presence of CAN should lead to further awareness of possible complications and optimal control of risk factors. Knowledge of early auto-nomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta blockers, proven to be effective for patients with CAN. Objectives: 1. To as-sess the cardiac autonomic function in patients with Type2 Diabetes Mellitus (T2DM) for detection of CAN. 2. To evaluate the relationship between CAN and duration of diabetes, and glycemic control in Type 2 DM. Materials and Methods: This is a case-control study conducted in Sri DevarajUrs Medical College, Tamaka, Kolar. Sixty patients (Cases) of T2 DM aged > 40 years admitted/visiting Diabetic clinic in R.L Jalappa hospi-tal and 60 healthy non diabetic controls matched for age and sex and satisfied the inclusion and exclusion criteria and gave informed consent for the study were included in the study. All the cases and controls have undergone standard bedside cardiac autonomic function tests. They were evaluated for glycemic control with FBS, PPBS and HbA1c levels. Cases were divided into sub-groups depending on duration of diabetes and glycemic control. The relation between CAN and duration of diabetes and glycemic control was deter-mined by Statistical analysis. Results: 60 cases with diabetes and 60 controls without diabetes were includ-ed in the study. Mean age of cases was 52.38 and controls was 51.97 years. There was no significant differ-ence in age between two groups because of matching. 36 males and 24 females were included in both cases and controls.There was no difference in sex distribution which can be attributed to matching of subjects during data collection. The mean duration of diabetes among cases was 7.28 ± 3.61 years. CAN was present in 21 (35%) of diabetic patients, 13 (21.6%) cases had early features of CAN, whereas CAN was present in 2 (3.3%) of controls and was absent in 86.6% of controls. In the study it was observed that mean age of dia-betics without CAN was 48.54 ± 5.7 years, Early CAN was 52 ± 6.17 and Definitive CAN was 57.38 ± 7.2 yrs. When cases were grouped according to duration of diabetes < 5 years and >5 years, 17.6 % and 41.8% of the cases in each group respectively had CAN, which is significant. About 85.7% of the cases who had CAN have had diabetes for a duration greater than 5 years. Among cases with HbA1c levels > 7%, about 54.54% had definitive CAN and 33.3% had Early CAN. It was observed that there was significant association be-tween increased HbA1c levels and CAN. Conclusion: The present study suggests Cardiac Autonomic Neurop-athy is common in Diabetics compared to healthy individuals. Cardiac Autonomic Neuropathy is associated with increase in the age of the patient and duration of diabetes. Cardiac autonomic neuropathy is associated with poor glycemic control. KeyWords: Cardiac Autonomic Neuropathy, Glycemic Control, HbA1c, Autonomic Function Tests, Type 2 Diabetes Mellitus.

Minimal ensemble based on subset selection using ECG to diagnose categories of CAN

Background and objective:Early diagnosis of cardiac autonomic neuropathy (CAN) is critical for reversing or decreasing its progression and prevent complications. Diagnostic accuracy or precision is one of the core requirements of CAN detection. As the standard Ewing battery tests suffer from a number of shortcomings, research in automating and improving the early detection of CAN has recently received serious attention in identifying additional clinical variables and designing advanced ensembles of classifiers to improve the accuracy or precision of CAN diagnostics. Although large ensembles are commonly proposed for the automated diagnosis of CAN, large ensembles are characterized by slow processing speed and computational complexity. This paper applies ECG features and proposes a new ensemble-based approach for diagnosis of CAN progression. MethodsWe introduce a Minimal Ensemble Based On Subset Selection (MEBOSS) for the diagnosis of all categories of CAN including early, definite and atypical CAN. MEBOSS is based on a novel multi-tier architecture applying classifier subset selection as well as the training subset selection during several steps of its operation. Our experiments determined the diagnostic accuracy or precision obtained in 5 × 2 cross-validation for various options employed in MEBOSS and other classification systems. ResultsThe experiments demonstrate the operation of the MEBOSS procedure invoking the most effective classifiers available in the open source software environment SageMath. The results of our experiments show that for the large DiabHealth database of CAN related parameters MEBOSS outperformed other classification systems available in SageMath and achieved 94% to 97% precision in 5 × 2 cross-validation correctly distinguishing any two CAN categories to a maximum of five categorizations including control, early, definite, severe and atypical CAN. ConclusionsThese results show that MEBOSS architecture is effective and can be recommended for practical implementations in systems for the diagnosis of CAN progression.

Diagnostic Accuracy of Random ECG in Primary Care for Early, Asymptomatic Cardiac Autonomic Neuropathy.

Cardiac autonomic reflex tests (CARTs) are time consuming and require patient cooperation for detecting cardiac autonomic neuropathy (CAN). Heart rate variability (HRV) analysis requires less patient cooperation and is quicker to complete. However the reliability of HRV results as a clinical tool, with respect to length of recording and accuracy of diagnosis is inconclusive. The current study investigated the reproducibility associated with varying length of recording for early CAN (eCAN) assessment. Participants were 68 males, 72 females with average age of 55 for controls and 63 for early CAN. Inclusion criteria were that participants were medication free and presented with no comorbidities. ECGs of control and eCAN were recorded and heart rate changes analyzed with the fast Fourier transform (FFT) and Lomb-Scargle periodogram (LSP). Ten-second to 5-minute recordings were extracted from a 15-minute lead-II ECG and accuracy in assessment of eCAN determined. The eCAN group was older ( P < .001) and systolic blood pressure was higher ( P < .01). HDL-cholesterol was also higher in the eCAN group ( P < .05). HRV analysis showed that both FFT and LSP results were significantly different between eCAN and control down to a 10-second ECG length for low frequency (LSP: P = .013, FFT: P = .024) and high frequency (HF-LSP: P = .002, FFT: P = .002) power. eCAN assessment was optimal down to 90-second recordings with a sensitivity of 100% and specificity of 29.49%. HRV is suitable for clinical practice from ECG recordings of more than 90 seconds with high accuracy and repeatability within a session for each participant.