Diagnosis Of Cardiovascular Autonomic Neuropathy Research Articles

Predictive value of heart rate variability and electrochemical skin conductance measurements for cardiovascular autonomic neuropathy persistence in type 2 diabetes and prediabetes: A 3-year follow-up study

ObjectiveThe study aimed to explore risk stratification approaches for cardiovascular autonomic neuropathy (CAN) in individuals with prediabetes and type 2 diabetes (T2DM) over a three-year follow-up period. MethodsParticipants underwent evaluations of autonomic function encompassing cardiovascular autonomic reflex tests (CARTs), baroreflex sensitivity (BRS), heart rate variability (HRV) in time domains (standard deviation of all normal RR intervals (SDNN)) and frequency domains (high frequency/low frequency ratio), and electrochemical skin conductance (ESC). The diagnosis of CAN relied on abnormal CART results. Subjects were categorized into 4 groups, based on their assessment of cardiac autonomic function at 3-year follow-up, relative to the presence or absence of CAN at baseline assessment: Persistent absence of CAN; Resolution of CAN; Progression to CAN; and Persistent CAN. ResultsParticipants with T2DM/prediabetes (n = 91/7) were categorized as: Persistent absence of CAN (n = 25), Resolution of CAN (n = 10), Progression to CAN (n = 18), and Persistent CAN (n = 45) groups. The Persistent absence of CAN group showed significant associations with SDNN. The Resolution of CAN group exhibited notable associations with mean HbA1C (follow-up), while the Progression to CAN group displayed a significant link with baseline estimated glomerular filtration rate. The Persistent CAN group demonstrated significant associations with SDNN and Sudoscan CAN risk score. Screening recommendations involve biennial to annual assessments based on risk levels, aiding in CAN detection and subsequent comprehensive and time-intensive autonomic function tests for confirmation. The study's findings offer improved risk categorization approaches for detecting CAN, which has relevance for shaping public health strategies.

QTC PROLONGATION, AN EARLY PREDICTOR OF CARDIOVASCULAR AUTONOMIC NEUROPATHY (CAN) IN POSTMENOPAUSAL DIABETIC WOMEN

To evaluate QTc interval in postmenopausal diabetic women in predicting cardiovascular autonomic neuropathy (CAN). A comparative cross-sectional study was conducted in the Cardiology Department of CMH Lahore and Sir Ganga Ram Hospital, Lahore, from April 2022- April 2023. A total of 80 women were included in the study, which was categorized into 40 pre and 40 postmenopausal women. Both groups were further divided into 20 diabetic and 20 non-diabetic women. A cut-off of 3-5 years was selected for natural menopause and 5-7 years for the available duration of type 2 diabetes. Blood samples were taken to determine serum estradiol levels in all 4 groups. Autonomic neuropathy was assessed by corrected QT interval (QTc), heart rate variability (HRV), Valsalva Ratio (VR), and resting heart rate (RHR). All variables were compared among groups by using SPSS version 20.0. Serum estradiol levels were significantly lowered in postmenopausal as compared to premenopausal women (p<0.001). QTc was significantly different (p=0.001) among all four groups. A statistically significant difference was found between premenopausal diabetic and postmenopausal diabetic groups (p=0.001) and between women of premenopausal non-diabetic and postmenopausal diabetic groups (p=0.003). Differences in RHR (p=0.840), HRV (p=0.084), and VR (p=0.129) were statistically nonsignificant among all four groups. A QTc prolongation is an important tool in investigating cardiac autonomic neuropathy (CAN) predisposition in postmenopausal diabetic women. Therefore, assessment of QTc prolongation could aid in early diagnosis of CAN in postmenopausal diabetic women.

The relationship between Cardiac Autonomic Dysfunction and Glycemic Variability in Pediatric Patients with Type 1 Diabetes Mellitus

Objective: Objective: Cardiovascular autonomic neuropathy (CAN) is defined as the impairment of cardiovascular autonomic control in patients with diabetes mellitus (DM) after excluding other causes. This study aims to investigate the relationship between glycemic variability and CAN in pediatric patients with type 1 DM Material and Methods: The study population consisted of children aged 8-18 who were being followed up with the diagnosis of type 1 DM. The diagnosis of CAN was made based on the heart rate variability indices and the results of the cardiovascular reflex tests.. Results: The study included 21 pediatric patients with type 1 diabetes mellitus (DM), consisting of 6 males and 15 females, with a median age of 13.94 years. Among them, 5 (23.8%) had early involvement, and 4 (19%) had definitive cardiovascular autonomic neuropathy (CAN). Patients with definitive CAN were significantly older and had a longer disease duration than those without CAN (p<0.05). Additionally, patients with definitive CAN had significantly higher hemoglobin A1c (HbA1c) levels (p<0.05). The time in the target blood glucose range (TIR) was significantly lower, while the time above the target blood glucose range (TAR) was significantly higher in patients with definitive CAN than in other patients (p<0.05). The standard deviation (SD) was also higher in patients with definitive CAN, but not significantly so (p>0.05). Conclusion: The study's findings indicated that TIR, which is one of the glycemic variability parameters, was significantly lower and TAR was considerably higher in children with definitive CAN, and SD was higher, albeit not significantly, in children with definitive CAN. Nevertheless, large-scale, prospective cohort studies are needed to fully elucidate the relationship between CAN and glycemic variability in pediatric type 1 DM patients.

Cardiovascular autonomic reflex tests using a handheld device in the diagnosis of cardiovascular autonomic neuropathy in patients with schizophrenia

Study objectiveThis study investigated whether schizophrenia and the duration of schizophrenia were associated with cardiovascular autonomic neuropathy (CAN) by using heart rate variability (HRV) as a marker. DesignCross-sectional study. SettingThe examinations were conducted at the Centre for Psychosis Research and at the Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. Participants240 patients with first-episode and chronic schizophrenia and 180 controls. InterventionsCAN was assessed by the cardiovascular reflex tests (CARTs): HR, RS ratio, E:I ratio, and VM using a handheld device. Main outcome measuresOne abnormal CART was interpreted as borderline CAN and ≥2 abnormal CARTs established definitive CAN. Borderline CAN and definitive CAN together was categorized as overall CAN. Analyses were adjusted for age, sex, smoking, overweight, and hypercholesterolemia. ResultsA total of 240 patients with schizophrenia (median age 42.5 [28.8, 52.3], 42.9 % women) and 180 controls (median age 45.8 [24.0, 60.1], 47.8 % women) were included, with 50.8 % of patients with schizophrenia having overall CAN compared to 27.2 % among controls. Dividing patients into patients with first-episode and chronic schizophrenia, 32.9 % vs 10 % (p < 0.001) and 59.1 % vs 41 % (p < 0.001) had overall CAN compared with controls, respectively. Schizophrenia was significantly associated with overall CAN (OR, 2.80; 95%CI, 1.75–4.50), with an OR of 2.31 (95%CI, 1.14–4.68) for first-episode schizophrenia and an OR of 2.97 (95%CI, 1.81–4.87) for chronic schizophrenia. ConclusionIt was demonstrated that a diagnosis of schizophrenia was associated with CAN. Patients with chronic schizophrenia had a significantly higher prevalence of CAN compared to patients with first-episode schizophrenia, suggesting an association between the duration of schizophrenia and CAN.

Возможности прогнозирования развития диастолической дисфункции левого желудочка у больных сахарным диабетом 1 типа

Aim: to identify risk factors for left ventricular (LV) diastolic dysfunction in type 1 diabetes (T1D) and evaluate their diagnostic and prognostic relevance for the development of DD. Patients and Methods: the study included 140 T1D patients (72 men and 68 women) with disease duration more than 3 years who are permanent residents of the Trans-Baikal region. The mean age was 32 years [26.5; 40] and the disease duration was 8 years [6; 11]. All patients were diagnosed with diabetes-associated cardiovascular autonomic neuropathy (CAN) and underwent echocardiography to evaluate LV DD using standard techniques. Serum levels of matrix metalloproteinases (MMPs), i.e., MMP-1, MMP-2, and MMP-3 were measured. In addition, the T(786)C NOS3 gene polymorphism was studied. Relevant risk factors for LV DD in patients with T1D were identified using binary logistic regression Results: 59 patients (42%) with T1D were diagnosed with diabetes-associated CAN. LV DD was diagnosed in 39 patients (27.8%) based on echocardiography. A significant increase in MMP-1 levels was revealed in T1D patients with LV DD, thereby illustrating the role of MMP activation for diabetic cardiomyopathy development. The risk of LV DD in patients with T1D is higher in homozygotic TT NOS3 Т(786)С genotype Conclusions: a model to predict the risk of LVDD based on MMP-1 level, the presence of diabetes-associated CAN, and homozygotic TT NOS3 gene variant was created using binary logistic regression. This model provides a timely diagnosis of diabetes-associated CAN in these patients. KEYWORDS: type 1 diabetes, left ventricular diastolic function, diabetic cardiomyopathy, matrix metalloproteinase-1, T(786)C NOS3 gene polymorphis FOR CITATION: Prosyanik V.I., Serebryakova O.V., Serkin D.M. Predicting the development of left ventricular diastolic dysfunction in type 1 diabetes. Russian Medical Inquiry. 2023;7(9):566–571 (in Russ.). DOI: 10.32364/2587-6821-2023-7-9-2.

Cardiovascular Autonomic Neuropathy Is Associated With Increased Glucose Variability in People With Type 1 Diabetes.

We investigated the association between the cardiovascular autonomic neuropathy (CAN) diagnosis and glucose variability (GV) in type 1 diabetes (T1D), as autonomic dysfunction previously has been associated with increased GV. CAN was assessed by three recommended cardiovascular reflex tests (CARTs). Glucose metrics were obtained from 10-day blinded continuous glucose monitoring (CGM). Between-group differences in GV indices were assessed by regression analyses in 24 participants with T1D with CAN and 24 matched control subjects without CAN. The CAN diagnosis was associated with 4.9% (95% CI 1.0, 8.7) higher coefficient of variation (CV) (P = 0.014), 0.7 mmol/L (0.3, 1.1) higher SD (P = 0.002) of glucose, and 1.4 mmol/mol (0.0, 2.7) higher mean amplitude of glycemic excursions (P = 0.047). Lower measures of CARTs were associated with higher CV, SD, and time above range values. The CAN diagnosis associates with a significantly higher GV in T1D, despite a high prevalence of routine CGM use.

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Is Associated With Disturbances in TCA, Lipid, and Glucose Metabolism.

IntroductionDiabetic cardiovascular autonomic neuropathy (CAN) is associated with increased mortality and morbidity. To explore metabolic mechanisms associated with CAN we investigated associations between serum metabolites and CAN in persons with type 1 diabetes (T1D).Materials and MethodsCardiovascular reflex tests (CARTs) (heart rate response to: deep breathing; lying-to-standing test; and the Valsalva maneuver) were used to diagnose CAN in 302 persons with T1D. More than one pathological CARTs defined the CAN diagnosis. Serum metabolomics and lipidomic profiles were analyzed with two complementary non-targeted mass-spectrometry methods. Cross-sectional associations between metabolites and CAN were assessed by linear regression models adjusted for relevant confounders.ResultsParticipants were median (IQR) aged 55(49, 63) years, 48% males with diabetes duration 39(32, 47) years, HbA1c 63(55,69) mmol/mol and 34% had CAN. A total of 75 metabolites and 106 lipids were analyzed. In crude models, the CAN diagnosis was associated with higher levels of hydroxy fatty acids (2,4- and 3,4-dihydroxybutanoic acids, 4−deoxytetronic acid), creatinine, sugar derivates (ribitol, ribonic acid, myo-inositol), citric acid, glycerol, phenols, phosphatidylcholines and lower levels of free fatty acids and the amino acid methionine (p<0.05). Upon adjustment, positive associations with the CAN diagnoses were retained for hydroxy fatty acids, tricarboxylic acid (TCA) cycle-based sugar derivates, citric acid, and phenols (P<0.05).ConclusionMetabolic pathways, including the TCA cycle, hydroxy fatty acids, phosphatidylcholines and sugar derivatives are associated with the CAN diagnosis in T1D. These pathway may be part of the pathogeneses leading to CAN and may be modifiable risk factors for the complication.

Diagnosis, staging, and associated conditions of cardiovascular autonomic neuropathy in Libyan patients with diabetes

Background: Cardiovascular autonomic neuropathy (CAN) can affect daily activities and patients' quality of life and evoke potentially life-threatening outcomes in diabetes mellitus (DM). Objectives: We aimed to identify and characterize CAN and associated disorders in Libyan patients with DM at National Diabetes Hospital. Patients and Methods: Ninety-nine patients with DM seen in the outpatient clinics from October 2017 to April 2018 at National Diabetes Hospital were prospectively evaluated. Assessments for CAN were made by clinical symptoms and signs, cardiovascular autonomic reflex tests, and echocardiogram. Patients with potentially confounding concomitant medical conditions were excluded. CAN is defined as possible (one abnormal cardiovagal test), confirmed (two abnormal such tests), and severe (with concomitant orthostatic hypotension and heart rate abnormality). Results: Sixty-two percent of the studied patients (mean age: 52 ± 1.5 years, 53% – female) with DM had CAN. CAN diagnosis was possible in 18% of these patients, confirmed in 6%, and severe in 38%. The presence of severe CAN was associated with hypoglycemic unawareness (P = 0.01), dyslipidemia (P = 0.012), and microvascular diabetic complications (P = 0.04). Conclusions: In this cohort of relatively old and high-risk cardiovascular disease, patients with diabetes, uncontrolled blood pressure, associated dyslipidemia, presence of microvascular complication of diabetes, and history of hypoglycemic unawareness were strongly associated with a severe form of cardiac autonomic neuropathy with potentially serious clinical consequences. Larger and more detailed studies are needed to elucidate further the complex association between hypoglycemia and cardiac autonomic dysfunction.

Cardiovascular autonomic neuropathy and the impact on progression of diabetic kidney disease in type 1 diabetes

IntroductionWe investigated the association between cardiovascular autonomic neuropathy (CAN) and decline in kidney function in type 1 diabetes.Research design and methodsWe included 329 persons with type 1 diabetes. CAN was...

Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients.

Aims/IntroductionCardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.Materials and MethodsStandardized CARTs (R‐R response to paced breathing, Valsalva, postural changes) and digitized 12‐lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R‐R intervals (SDNN) and the root mean square of successive differences between normal‐to‐normal R‐R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG‐derived CAN and CARTs‐defined CAN.ResultsParticipants with CARTs‐defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut‐off points of ECG‐derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30–0.51) for the optimal cut‐off point, showing fair agreement with CARTs‐defined CAN. Combining SDNN and rMSSD optimal cut‐off points does not provide additional predictive power for CAN.ConclusionsThese analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care.

Early detection of cardiovascular autonomic neuropathy: A multi-class classification model based on feature selection and deep learning feature fusion

The conventional diagnostic process and tools of cardiovascular autonomic neuropathy (CAN) can easily identify the two main categories of the condition: severe/definite CAN and normal/healthy without CAN. Conventional techniques encounter significant challenges when identifying CAN in its early or atypical stages due to the inherent imbalanced and incompleteness condition in the collected clinical multimodal data, including electrocardiogram (ECG) data from ECG sensors, blood chemistry, podiatry, and endocrinology features. Therefore, most detection tools and techniques are limited to binary CAN classification. However, early diagnosis of CAN or diagnosis of the atypical stages of CAN is more important than the diagnosis of severe CAN, which, in fact, is easily identifiable with a few diagnostic reports. In this paper, we propose a novel multi-class classification approach for timely CAN detection. The proposed classification algorithm develops a multistage fusion model by combining feature selection and multimodal feature fusion techniques. The proposed method develops a performance criterion-based feature selection technique to guarantee highly significant features. A multimodal feature fusion technique was developed using deep learning feature fusion and selected original features. The experimental results obtained from testing with a large CAN dataset indicate that the proposed algorithm significantly improved the diagnostic accuracy of CAN compared to conventional Ewing battery features. The algorithm also identified the early or atypical stages of CAN with an AUC score of 0.931 using leave-one-out cross-validation.

Cardiovascular autonomic neuropathy in diabetes: Pathophysiology, clinical assessment and implications.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition that mainly occurs in long-standing type 2 diabetes patients but can manifest earlier, even before diabetes is diagnosed. CAN is a microvascular complication that results from lesions of the sympathetic and parasympathetic nerve fibers, which innervate the heart and blood vessels and promote alterations in cardiovascular autonomic control. The entire mechanism is still not elucidated, but several aspects of the pathophysiology of CAN have already been described, such as the production of advanced glycation end products, reactive oxygen species, nuclear factor kappa B, and pro-inflammatory cytokines. This microvascular complication is an important risk factor for silent myocardial ischemia, chronic kidney disease, myocardial dysfunction, major cardiovascular events, cardiac arrhythmias, and sudden death. It has also been suggested that, compared to other traditional cardiovascular risk factors, CAN progression may have a greater impact on cardiovascular disease development. However, CAN might be subclinical for several years, and a late diagnosis increases the mortality risk. The duration of the transition period from the subclinical to clinical stage remains unknown, but the progression of CAN is associated with a poor prognosis. Several tests can be used for CAN diagnosis, such as heart rate variability (HRV), cardiovascular autonomic reflex tests, and myocardial scintigraphy. Currently, it has already been described that CAN could be detected even during the subclinical stage through a reduction in HRV, which is a non-invasive test with a lower operating cost. Therefore, considering that diabetes mellitus is a global epidemic and that diabetic neuropathy is the most common chronic complication of diabetes, the early identification and treatment of CAN could be a key point to mitigate the morbidity and mortality associated with this long-lasting condition.

Screening Cardiovascular Autonomic Neuropathy in Diabetic Patients With Microvascular Complications Using Machine Learning: A 24-Hour Heart Rate Variability Study

Cardiovascular autonomic neuropathy (CAN) is one of the most overlooked complications associated with diabetes. It is characterized by damage in the autonomic nerves regulating heart rate and vascular compliance. Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical CAN and requires patient cooperation. In addition, appropriate timing (day/night) of CAN diagnostic test was not explored in the past. Therefore, a novel approach is proposed herein to investigate the feasibility of using heart rate variability (HRV) features over 24 hours embedded within machine learning algorithms to provide a complete screening for patients suffering from CAN. 24-hour Holter ECG data were acquired from a Bangladeshi cohort (n = 95 patients [75 Diabetic and 25 healthy]). HRV features were extracted from every 5-minute segment of the HRV signal and used as input to four machine learning algorithms for hourly training and testing. A complete hierarchical step by step diagnosis procedure (4 tests) was developed; namely test 1 to check for being healthy or diabetic; test 2 to check for any microvascular complications (including neuropathy such as CAN, peripheral neuropathy (DPN), nephropathy (NEP), and retinopathy (RET)) or not; test 3 to check for presence of only CAN; test 4 to check for combined or multiple complications along with CAN. The highest levels of performance were achieved with accuracy measures of 85.5% (test 1 - convolutional neural network (CNN)), 98.5% (test 2 - CNN), 98.3% (test 3 - one-class support vector machines (SVM)), and 90.9% (test 4 - random forest). Hours 7:00 AM and 7:00 PM were found to be most significant in the diagnosis of CAN in diabetic patients (test 1, 3, and 4). Early screening of CAN by our proposed models could help primary healthcare centers stratify the risk leading to early treatment in preventing sudden cardiac death due to silent myocardial infarction. The approach is considered to be simple and effective, especially for under-resourced clinical settings.

Combination of Composite Autonomic Symptom Score 31 and Heart Rate Variability for Diagnosis of Cardiovascular Autonomic Neuropathy in People with Type 2 Diabetes.

Objective Cardiovascular autonomic neuropathy (CAN) is a common but severe problem of diabetes, which a timely diagnosis may have important clinical implications. This study was carried out to investigate the diagnostic performance of Composite Autonomic Symptom Score 31 (COMPASS 31) combined with heart rate variability (HRV) for cardiovascular autonomic neuropathy in type 2 diabetes. Methods A total of 103 hospitalized subjects with type 2 diabetes were recruited in the study. All cases received clinical data collection, laboratory examination, and related complication examinations. Cardiovascular autonomic function was assessed using CARTs, COMPASS 31, and HRV analyses. A score of at least 2 based on CARTs was defined as CAN. Results Of the 103 subjects with type 2 diabetes, 41.8% were diagnosed with confirmed CAN. Participants with CAN had considerably higher COMPASS 31 scores. The CAN group showed a significant decrease in all HRV indices. COMPASS 31 scores and HRV indices were closely correlated with CARTs (P < 0.05). Receiver operating characteristics (ROC) curve results showed that COMPASS 31 score identified CAN with an AUC value of 0.816, while the AUC values of HRV indices were 0.648 to 0.919, among which SDNN and LF had the best diagnostic value, with the AUC values of 0.919 and 0.865, respectively. When combining COMPASS 31 score with SDNN and LF, the AUC value increased to 0.958, with a sensitivity of 90.7% and a specificity of 86.7%. Conclusions The combination of COMPASS 31 and HRV could improve the diagnostic performance of CAN in type 2 diabetes, which might be conducive to the diagnosis of CAN.

Diabetic Cardiovascular Autonomic Neuropathy, the Handgrip Test and Ambulatory Blood Pressure Monitoring Parameters: Are There Any Diagnostic Implications?

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. Cardiovascular reflex tests (CARTs) are the gold standard in the diagnosis of CAN, but the handgrip test is no longer recommended to be performed. Previously, the inverse association between the presence of hypertension and handgrip test abnormality was demonstrated and hypertension as major cause for excessive diastolic blood pressure rise during handgrip testing in diabetic individuals proposed. The aim of the present study is to describe more precisely the association between handgrip test and hypertension by performing ambulatory blood pressure monitoring (ABPM) among diabetic patients. A more comprehensive evaluation of the relationship between cardiovascular autonomic function, hypertension and the handgrip test was targeted using heart rate variability (HRV) analysis. Our study involved 163 patients with diabetes. Cardiovascular autonomic neuropathy was assessed by the CARTs and sustained handgrip test was performed. All patients underwent ABPM and HRV analysis well. CAN was diagnosed in 69 patients. Significant associations were found between the diastolic blood pressure increase in response to handgrip exercise and the 24-h (rho = 0.245, p = 0.003), daytime (rho = 0.230, p = 0.005) and night-time (rho = 0.230, p = 0.006) mean systolic and 24-h diastolic (rho = 0.176, p = 0.034) blood pressure values, systolic blood pressure load (rho = 0.252, p = 0.003) and systolic (rho = 0.236, p = 0.005) and diastolic (rho = 0.165, p = 0.047) hyperbaric impacts. Higher values of ambulatory blood pressure monitoring parameters are associated with greater increases in diastolic blood pressure during isometric handgrip exercise. Diastolic blood pressure elevations during the handgrip test are also correlated, in order to diminished heart rate variability parameters attributable to parasympathetic dysfunction highlighting the pivotal role of sympathetic overactivity in evolving handgrip test results. Our study provides further evidence on the inverse association between handgrip test abnormality and hypertension in diabetic patients.

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes

AimsTo investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. MethodsParticipants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). ResultsNinety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. ConclusionCAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Clinical Tools for Peripheral Neuropathy to Exclude Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Mellitus.

IntroductionAssessment for cardiovascular autonomic neuropathy (CAN) remains difficult in everyday clinical practice. We sought to examine the diagnostic utility of various simple tools for diabetic peripheral neuropathy (DPN) in the detection of CAN in type 2 diabetes mellitus.MethodsWe examined 153 type 2 diabetes mellitus subjects by various DPN tools (vibration perception threshold, 10 g Semmes-Weinstein monofilament, Ipswich touch test, NC-stat®/DPNCheck, neuropathy disability score) for the detection of CAN. CAN was diagnosed by the standardised cardiovascular autonomic reflex function tests.ResultsFor the diagnosis of CAN, assessment of small nerve fibre function (pinprick sensation, temperature perception) yielded a very high negative predictive value (97%), with high sensitivity (89%) and moderate specificity (73%). The vibration perception threshold was second in diagnostic utility (91% negative predictive value, 62% sensitivity and 75% specificity).ConclusionsBased on their high negative predictive value, simple tools for DPN may prove useful to exclude CAN in type 2 diabetes mellitus. These encouraging results merit further evaluation to enable wider screening for CAN.

Prevalence and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy in Beijing, China: A Retrospective Multicenter Clinical Study.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition occurring among diabetic patients especially those with long duration of disease. Whereas incidences and treatment of CAN has been well described for Western populations, fewer studies have been conducted among the Chinese. This study, therefore, aimed to assess the prevalence of CAN among sampled Chinese diabetic patients. Accordingly, 2,048 participants with a history of type 1 diabetes mellitus (T1DM, 73) and type 2 diabetes mellitus (T2DM, 1975) were randomly sampled from 13 hospitals. Patients’ biodata were recorded, and autonomic nervous system function tests performed to aid in the preliminary diagnosis of CAN. The final CAN diagnosis was based on the Ewing’s test in which heart rate variation (HRV) values were evaluated through deep-breathing (DB), lying-to-standing (LS), and Valsalva (V) tests. Systolic blood pressure (SBP) variation values were also evaluated through LS. In the T1DM group, 61.6% patients were diagnosed with CAN and no differences were observed in the baseline and clinical data between this group and those without CAN (P > 0.05). In the T2DM group, 62.6% patients were diagnosed with CAN and statistically significant differences were found between the CAN and non- CAN group with regards to age, duration of diabetes, metformin treatment, retinopathy, and hypertension history (P < 0.05). The most common manifestations of CAN included weakness (28.6%), dizziness (23.4%), frequent urination (19.6%), upper body sweating (18.3%), and nocturia (15.9%). Additionally, duration of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. On diagnosis, a combination of the V test + LS test provided the highest sensitivity of detecting CAN among T1DM group (sensitivity = 97.6%, AUC = 0.887) while for T2DM category, DB test had the highest sensitivity (83.6%), and maximal AUC (0.856) was found with V test + DB test. The overall prevalence of diabetes with CAN in the study was up to 63%.

2245-PUB: The Epidemiology and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy: A Multicenter Clinical Study

Objective: To evaluate the risk factors of cardiovascular autonomic neuropathy(CAN) in Chinese diabetic patients, estimate the optimal CAN diagnostic method to different diabetics, assess CAN prevalence in our dataset. Methods: 2, 048 subjects randomly sampled from 13 hospitals were available for data analysis, including 73 type 1 diabetes mellitus (T1DM) and 1, 975 type 2 diabetes mellitus (T2DM). The general data of patients were collected and sympathetic and parasympathetic function tests were executed to CAN preliminary diagnosis. The final CAN diagnosis was based on Ewing's test in which heart rate variation (HRV values were evaluated through deep-breathing (DB), lying-to-standing (LS), Valsalva (V) tests and systolic blood pressure (SBP) variation values was evaluated through LS. Results: 1) In T1DM group, 61.64% patients were diagnosed with CAN; baseline data and clinical data of CAN group had no difference with those of none-CAN group (P&amp;gt;0.05);while in T2DM group, 62.58% patients were diagnosed with CAN; there were significant differences between CAN and none-CAN group in age, course of the disease, use of metformin, course of metformin treatment, retinopathy and hypertension history (P&amp;lt;0.05). 2) Among various symptoms in CAN group, most frequent symptoms were weakness (28.65%), dizziness (23.42%), frequent urination (19.59%), upper body sweating (18.35%) and enuresisnocturna (15.93%). 3) Course of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. 4) For T1DM, the optimal CAN diagnostic method was Vtest+LStes (sensitivity=97.62% , AUC=0.887); while for T2DM, DBtest had the highest sensitivity (83.62%) and Vtest+DBtest had the maximal AUC (0.856). Conclusion: The prevalence of diabetes with CAN was up to 63%.The course of disease and age are independent risk factors of CAN in TIDM and T2DM, respectively. Furthermore, Vtest+LStest and Vtest+DBtest were the optimal CAN diagnostic method for T1DM and T2DM, respectively. Disclosure Q. Pan: None. L. Guo: None. X. Wang: None. L. Zhang: None. T. Xian: None. F. Man: None. L. Liu: None.