Cardiovascular Autonomic Neuropathy In Patients Research Articles

Association of Continuous Glucose Monitoring-Derived Glycemia Risk Index With Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes Mellitus: A Cross-sectional Study.

The glycemia risk index (GRI) is a new composite continuous glucose monitoring (CGM) metric for weighted hypoglycemia and hyperglycemia. We evaluated the association between the GRI and cardiovascular autonomic neuropathy (CAN) and compared the effects of the GRI and conventional CGM metrics on CAN. For this cross-sectional study, three-month CGM data were retrospectively analyzed before autonomic function tests were performed in 165 patients with type 1 diabetes. CAN was defined as at least two abnormal results of parasympathetic tests according to an age-specific reference. The overall prevalence of CAN was 17.1%. Patients with CAN had significantly higher GRI scores, target above range (TAR), coefficient of variation (CV), and standard deviation (SD) but significantly lower time in range (TIR) than those without CAN. The prevalence of CAN increased across higher GRI zones (P for trend <.001). A multivariate logistic regression analysis, adjusted for covariates such as HbA1c, demonstrated that the odds ratio (OR) of CAN was 9.05 (95% confidence interval [CI]: 2.21-36.96, P = .002) per 1-SD increase in the GRI. TIR and CV were also significantly associated with CAN in the multivariate model. The area under the curve of GRI for the prediction of CAN (0.85, 95% CI: 0.76-0.94) was superior to that of TIR (0.80, 95% CI: 0.71-0.89, P for comparison = .046) or CV (0.71, 95% CI: 0.57-0.84, P for comparison = .049). The GRI is significantly associated with CAN in patients with type 1 diabetes and may be a better CGM metric than TIR for predicting CAN.

Low muscle strength rather than low muscle mass is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing’s protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN.

Impacts of Chemerin Levels and Antioxidant Capacity on the Severity of Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes and Prediabetes.

Existing evidence supports an association between chemerin levels and cardiovascular risk, while reduced thiol levels are linked to diabetes mellitus. It is hypothesized that chemerin may contribute to autonomic dysfunction and cardiovascular risk in type 2 diabetes mellitus (T2DM), potentially mediated by the antioxidant capacity of patients with well-controlled T2DM and prediabetes. Comprehensive cardiovascular autonomic testing and biomarker assessments were conducted for all participants. The severity of cardiovascular autonomic neuropathy (CAN) was evaluated using the composite autonomic scoring scale (CASS). A mediation model was employed to explore the potential relationships among chemerin levels, antioxidant capacity (indicated by thiol levels), and CAN severity (indicated by CASS values). A total of 184 participants were enrolled in this study, comprising 143 individuals with T2DM and 40 individuals with prediabetes. The findings reveal a significant negative association between thiols levels (r = -0.38, p < 0.0001) and the CASS values, while a positive association is observed between chemerin levels (r = 0.47, p < 0.0001) and the CASS values. Linear regression analysis identified chemerin and thiols as independent variables significantly associated with CASS values. Subsequent mediation analysis elucidated that thiols levels act as mediators in the relationship between elevated chemerin levels and an increased CASS value. This study shows that poor cardiovascular function, higher chemerin levels, and reduced antioxidant capacity coexist in individuals with T2DM and prediabetes. Mediation analysis suggests a pathophysiological link between high chemerin levels and low antioxidant capacity, adversely impacting CAN severity.

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.

Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson's Disease.

BackgroundAutonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.Materials and MethodsEighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.Results and ConclusionThere was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.

Cardiovascular Autonomic Neuropathy in Patients with Diabetes in Cotonou, Benin: A Cross-Sectional Study

Background Diabetes mellitus is well known as a major risk factor for cardiovascular diseases. Cardiovascular autonomic neuropathy is one of the diabetes complications that has a major impact on cardiovascular morbidity and mortality in patients with diabetes. Aim : To determine the prevalence of cardiovascular autonomic neuropathy in patients with diabetes attending the diabetic center in Cotonou and to identify its risk factors. Materials and Methods : It was a cross-sectional study. Cardiovascular autonomic neuropathy was identified using deep breathing test, standind test and the blood pressure response to standing test (orthostatic hypotension). Chi square test was used for statistical analysis and différence was considered significant when p&lt;0.05. Results : A total of 405 subjects were included in the study. Their mean age was 53.67±11,68 years and the mean diabetes duration was 6.66 years. The prevalence of cardiovascular autonomic neuropathy was 65.9%. Regarding the severity of the complication in neuropathic patients, 51.7% of them had an early neuropathy, 41.2% have presented a moderate neuropathy and 7.1% have presented a severe neuropathy. Factors associated with cardiovascular autonomic neuropathy were age of patients (p = 0.0002), diabetes duration (p = 0.0012), hypertension (p =0.0015), dyslipidemia (p = 0.027) and high pulsed blood pressure (p = 0.032) Conclusion : Cardiovascular autonomic neuropathy is a very frequent complication of diabetes mellitus. Unfortunately this complication of diabetes is not often explored in the patient's follow-up examination. As this complication is recognised to be associated with high cardiovascular morbidity and mortality, systematic screening can be recommanded in patients with long duration of diabetes or presenting an other cardiovascular risk factor.

Quantitative sensory testing can effectively predict cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

Cardiovascular autonomic neuropathy (CAN) is one of the most serious types of diabetic autonomic neuropathy and is a class of small fibre neuropathy. Among many inspection methods, quantitative sensory testing is an effective and convenient method for diagnosing diabetic small fibre neuropathy. This cross-sectional study aimed to identify the correlation between the development of cardiovascular autonomic neuropathy and quantitative sensory testing parameters in patients with type 2 diabetes mellitus. A total of 266 participants with type 2 diabetes mellitus from Nanjing Drum Tower Hospital were enrolled in this study, and each of them received cardiovascular reflex tests (CARTs) and quantitative sensory testing, including testing of cold, warm, cold pain, and heat pain detection thresholds (CDT, WDT, CPT, and HPT, respectively). The results of CARTs were compared with the thermal detection thresholds in quantitative sensory testing by using SPSS 26.0. A total of 266 participants were divided into the CAN group, early CAN (ECAN) group, and without CAN (NCAN) group. There were significant differences in quantitative sensory testing parameters among three groups, and CARTs presented a positive correlation with the WDT and HPT and a negative correlation with the CDT. Moreover, after adjusting for age, sex, diabetes duration, and other influencing factors, WDT, HPT, and CDT were independent risk factors for cardiovascular autonomic neuropathy. The thermal detection thresholds, including cold, warm, and heat pain detection thresholds, in quantitative sensory testing were found to be significantly related to the results of CARTs. Some thermal detection thresholds were independent risk factors for cardiovascular autonomic neuropathy. Therefore, this study showed that quantitative sensory testing has a reliable predictive ability for the occurrence and development of cardiovascular autonomic neuropathy.

Risk factors of cardiovascular autonomic neuropathy in patients with prediabetes and coronary artery disease

Risk factors of cardiovascular autonomic neuropathy in patients with prediabetes and coronary artery disease

Cardiovascular autonomic neuropathy in patients with schizophrenia

Background Cardiovascular autonomic neuropathy (CAN) is an independent predictor of cardiovascular disease (CVD) in patients with diabetes as well as in patients with pre-diabetes and metabolic syndrome. Patients with schizophrenia have an increased rate of metabolic syndrome, pre-diabetes and diabetes as compared to the general population. Despite of this, occurrence CAN has not been investigated in patient with schizophrenia. Therefore, the aims of this study were (1) to evaluate the feasibility testing for CAN with a new clinical tool and (2) report the prevalence of early and manifest CAN in patients with schizophrenia. Methods and results Patients with diagnosed schizophrenia and with a disease duration ≥10 years were matched 1:1 on age and gender at screening with psychiatric healthy controls. CAN was defined as ≥ two abnormal standard cardiovascular autonomic reflex tests (lying-to-standing, deep breathing, and Valsalva maneuver) using the VagusTM device. A total of 46 patients with schizophrenia were included and matched to psychiatric healthy controls. Manifest CAN were more frequently presented in patients with schizophrenia (39% vs. 6% for controls, p<.0001). Sensitivity analysis of 41 subjects with schizophrenia without diabetes matched to 41 psychiatric healthy controls, showed similar results (37% vs. 5% for controls, p<.0001). Conclusion CAN is highly prevalent in patients with schizophrenia. Testing for CAN is feasible and might be a new clinically tool for detecting early stages of CVD in patients with schizophrenia.

Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus

The impairment of cardiovascular autonomic control among the underdiagnosed complication of diabetes mellitus (DM) with a high prevalence rate of up to 60% in type 2 DM (T2DM). Cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality, arrhythmia, silent ischemia, any major cardiovascular event, and heart failure. We aimed to evaluate cardiovascular autonomic activity by different physiological maneuvers, study risk factors for diabetic CAN including age, gender, duration of diabetes, body mass index (BMI), and glycemic control, and correlate CAN stage with risk factors. One hundred and forty-two T2DM patients consisted of 62 males and 80 females and 100 volunteers as a control sample. Cardiac autonomic functions were assessed by Ewing's tests. Glycated hemoglobin (HbA1c), body weight, height, body mass index (BMI), and waist-hip ratio (WHR) were also measured. Cardiovascular autonomic functions and Ewing scores were significantly different in people with diabetes when compared with control healthy subjects. Ewings test values and Ewing scores were significantly different between diabetics with and without CAN and within patients with different CAN staging. People with diabetes with CAN have a significantly longer duration of disease when compared to those without CAN. A strong association has been found between CAN severity and patient age, duration of disease, HbA1c severity, and the WHR (P < 0.001) but not with BMI. The duration of disease and HbA1c level appear to be associated with the development of CAN (P = 0.001 and P = 0.008, respectively). The poorer glycemic control and the longer the duration of the disease, the higher the prevalence of CAN in T2DM. Age, duration of disease, WHR, and HbA1c are well correlated with the severity of CAN. Parasympathetic impairment is more sensitive to the detection of autonomic dysfunctions than do sympathetic impairment.

The Role of Electrochemical Skin Conductance as a Screening Test of Cardiovascular Autonomic Neuropathy in Patients with Parkinson's Disease.

Autonomic disorders have been recognized as an important non-motor feature in Parkinson’s disease (PD). However, there is a paucity of information on the presence and severity of cardiovascular autonomic neuropathy (CAN) among different motor phenotypes. The aims of this study were to examine the feasibility of electrochemical skin conductance (ESC) measured by Sudoscan as a screening service for CAN in patients with PD and investigate the severity of CAN among different motor phenotypes. Design: This was a cross-sectional observational study that enrolled 63 patients with PD. Patients were divided into three phenotypes, postural instability/gait difficulty (PIGD), tremor-dominant (TD), and akinetic-rigid (AR), according to their motor symptoms. Cardiovascular autonomic function was measured, and the presence and severity of CAN was determined according to the composite autonomic scoring scale (CASS). Functional scores were measured by the Hoehn and Yahr (HY) stage and the Unified Parkinson’s Disease Rating Scale (UPDRS). The median HY stage was 2.0 [1.5, 3.0]. Median UPDRS total score was 23.0 (17.5, 30.5), 10.0 (6.0, 11.0) and 14.0 (6.3, 23.8) in groups of PIGD, TD and AR, respectively (p = 0.001). Mean CASS was 1.7 ± 1.3, 0.6 ± 0.4, and 1.8 ± 1.5 in groups of PIGD, TD and AR, respectively (p = 0.204). Although the ESC was not strongly associated with the cardiovascular autonomic parameters, the CAN risk score provided by Sudoscan significantly correlated with parameters of cardiovascular autonomic function, including heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS). By receiver-operating characteristic (ROC) analysis, if a patient’s CAN risk score is higher than 33.5 (%), it is recommended to be aware of the presence of CAN even in PD patients who are asymptomatic. The area under ROC curve was 0.704. Based on our results, CAN risk score may be used for screening of CAN in patients with PD before resorting to the more sophisticated and specific, but ultimately more time-consuming, complete autonomic function testing.

534-P: The Association between Glycemic Variability and Cardiovascular Autonomic Neuropathy in Patients with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy

Aim: Describe the relationships between cardiovascular autonomic neuropathy (CAN) and glucose variability (GV) in patients with DM1 on continuous subcutaneous insulin infusion therapy (CSII). Methods Observational retrospective study (n=89). CAN was assessed by heart rate variability (HRV) in response to deep breathing, standing, Valsalva’s maneuver, and the amplitude of the low (LFa) and high (HFa) frequency of HRV. The standard deviation (SD), the coefficient of variation (CV) and time in range (TIR) were calculated from the capillary blood measurements downloaded of CSII (the mean of glucose capillary assessments was 5.8/day). Results The mean age was 38±13 and their average duration of DM1 was 22±10 years. The prevalence of CAN was 36% (95%CI: 27-46). The population characteristics according to the presence of CAN are summarized in Table 1. The age and the duration of diabetes correlated negatively with LFa (r= -0.496, P &amp;lt; 0.001) and HFa (r= -0.510, P &amp;lt; 0.001). Separate multivariate binary logistic models were constructed for clinical and GV parameters introducing CAN as dependent variable. Only the age (expB 1.1; CI 1.04-1.15. P &amp;lt; 0.001) was associated with CAN in the fully adjusted model. Conclusions Age and duration of diabetes, but not GV parameters, appear to be associated with CAN in our cohort of patients with DM1 on CSII. Disclosure L. Nattero-Chávez: None. J. Quiñones Silva: None. N. Bengoa: None. M. Fernández Argüeso: None. L. Montanez: None. E. Fernández Durán: None. B. Dorado: None. B. Arias Zamorano: None. E. Lecumberri: None. M. Luque Ramírez: None. Funding Menarini Group

Role of Heart Rate Response to Standing and Valsalva Manoeuvre Measurement in Diagnosing Cardiovascular Autonomic Neuropathy in Patients With Diabetes Mellitus.

Diabetes is an iceberg disease with many complications like cardiovascular disease &diabetic neuropathy. One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy (CAN), Autonomic nervous system dysfunction is one of the significant complications of diabetes mellitus and this is generally associated with a poor prognosis. Standard cardiovascular reflex tests are used to assess cardiovascular autonomic function. These include changes in heart rate during standing up and, Valsalva manoeuvre to assess cardiac parasympathetic activity. Aim: To analyse the role of heart rate during standing up and , Valsalva manoeuvre in diagnosing Cardiac Autonomic Neuropathy.

Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus and its association with serum omentin and leptin.

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

Correlation between serum bilirubin and cardiovascular autonomic neuropathy in patients with type 2 diabetes

Objective: To investigate the correlation between serum bilirubin and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes mellitus patients. Methods: A total of 369 patients with type 2 diabetes mellitus who were hospitalized at the Department of Endocrinology, Nanjing Jinling Hospital from April 2017 to October 2018 were enrolled, including 226 males and 143 females, with an average age of (54.6±12.1) years. According to cardiovascular reflex tests (CARTs), all the patients were divided into Non CAN group(149 patients without CAN) and CAN group (220 patients complicated with CAN). The difference of serum bilirubin levels between the two groups was compared. The differences of CARTs and the incidence of CAN were compared by tertiles of serum bilirubin levels. The binary logistic regression was used to analyze the risk factors for diabetic cardiovascular autonomic neuropathy. Results: The serum total bilirubin [(9.28±2.74) μmol/L vs (11.08±2.98) μmol/L, P<0.001], direct bilirubin [(3.17±1.20) μmol/L vs (3.71±1.24) μmol/L, P<0.001] and indirect bilirubin levels [(6.11±1.89) μmol/L vs (7.37±2.10) μmol/L, P<0.001] in CAN group were significantly lower than that in Non CAN group. With the increase of serum bilirubin, the incidence of CAN decreased (P<0.01). Multivariate Logistic regression analysis showed that serum total bilirubin (OR=0.819, 95%CI: 0.744-0.901, P<0.001), direct bilirubin (OR=0.739, 95%CI: 0.601-0.908, P=0.004) and indirect bilirubin (OR=0.749, 95%CI: 0.653-0.860, P<0.001) were inversely correlated with the incidence of CAN. Conclusions: Within the physiological range, lower level of serum bilirubin is inversely correlated with the incidence of CAN. It is noteworthy to screen diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus who had a lower serum bilirubin level.

HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration.

BackgroundVariability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years).MethodsFor each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively.ResultsThose with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS.ConclusionHbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.

Clinical factors associated with the recovery of cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus

BackgroundCardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in diabetes patients. Although several risk factors for CAN progression have been established, whether CAN is reversible remains unclear and the clinical factors associated with CAN recovery have not been identified. This study aimed to determine clinical factors related to CAN recovery.MethodsType 2 diabetes patients with CAN but free of cardiovascular disease at baseline were enrolled and followed for 2–3 years in this retrospective longitudinal study. CAN was classified as early (one abnormal parasympathetic test), definite (two or more abnormal parasympathetic tests), severe (definite plus orthostatic hypotension), or atypical (early plus orthostatic hypotension or orthostatic hypotension alone) based on Ewing’s method. CAN recovery was classified as partial or complete: Partial recovery was defined as one-step improvement in CAN stage (early to normal, definite to early, or severe to definite), including the disappearance of only one abnormal result in any stage. Complete recovery was defined as normalization from definite or severe CAN.ResultsAmong 759 subjects with CAN, 29.9% (n = 227) experienced CAN recovery, and 1.2% (n = 9) recovered completely. In a multivariate model, younger age (odds ratio [OR] per 5-year decrease 1.49; 95% confidence interval [CI] 1.25–1.78, P < 0.001), shorter duration of diabetes (OR per 5-year decrease 1.33; 95% CI 1.05–1.67, P = 0.016), presence of micro/macroalbuminuria (OR 0.34; 95% CI 0.15–0.78, P = 0.011), body weight reduction (OR per 1-kg decrease 1.11; 95% CI 1.02–1.21, P = 0.016), and HbA1c reduction (OR per 1% decrease 1.32; 95% CI 1.05–1.67, P = 0.019) were significantly associated with composite events of partial and complete CAN recovery. Age had the highest relative significance among the associated clinical factors. In addition, younger age was the only significant factor in complete CAN recovery.ConclusionsYounger age was the most important factor in CAN recovery in subjects with type 2 diabetes, including recovery from the definite or severe stage. HbA1c reduction, body weight reduction, no concurrent micro/macroalbuminuria, and shorter duration of diabetes were also significantly associated with CAN recovery.

The Association between Urinary N-Acetyl-ß-D-Glucosaminidase and Cardiovascular Autonomic Neuropathy in Patients with Diabetes

Background: Cardiovascular autonomic neuropathy (CAN) is a microvascular complication of diabetes, which involves autonomic nerve fibers innervating the heart and vessels, resulting in increased cardiovascular morbidity and mortality. Previous studies reported that diabetic CAN is related to microalbuminuria. However, it is unclear whether CAN is related with urinary N-acetyl-β-D-glucosaminidase (uNAG), which was suggested as an early marker of renal tubular injury in diabetic nephropathy recently. Methods: Cross-sectional data of 1052 patients with diabetes were analyzed who had tests for uNAG and autonomic function test at outpatient clinic. The presence and severity of CAN were assessed by the five autonomic function tests. Results: The association between uNAG and the presence of CAN in patients with type 1 diabetes (T1D) (n=161) was significant in multivariate analysis (OR 1.20, 95% CI 1.03-39; p = 0.018) after correction of variables including age, duration of diabetes, glycemic index and albuminuria, but it was insignificant in patients with type 2 diabetes (T2D) (n=891). Among quartile groups divided by uNAG levels, prevalence of CAN was significantly increased across with higher quartiles of uNAG level only in patients with T1D (p = 0.013). The association between uNAG and the total CAN score, assessed as the severity of CAN, was significant in both patients with T1D (p = 0.033) and T2D (p = 0.006) in multivariate analyses. Conclusion: Elevated uNAG is associated with the prevalence of CAN only in patients with T1D, and it is also related to the severity of CAN in both patients with T1D and T2D. It suggests that elevated uNAG might be a potential marker for the development and progression of CAN in patients with diabetes. Disclosure M. Choi: None. J. Jun: None. G. Kim: None. S. Jin: None. K. Hur: None. M. Lee: None. J. Kim: None.

Anemia, bilirubin, and cardiovascular autonomic neuropathy in patients with type 2 diabetes.

To investigate the relationship among anemia, physiological serum bilirubin levels, and cardiovascular autonomic neuropathy (CAN) in subjects with type 2 diabetes. In total, 2230 subjects with type 2 diabetes were evaluated in this cross-sectional study. CAN was diagnosed with a cardiovascular reflex test. The prevalence of anemia was greater in subjects with CAN. In multivariable analysis, the relationship between anemia and CAN remained statistically significant after adjusting for the risk factors (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.07–1.80, P = .015). Additional adjustment for serum bilirubin concentrations abolished this relationship (OR 1.20, 95% CI 0.91–1.58, P = .189). Anemia is positively associated with the prevalence of CAN in subjects with type 2 diabetes. In addition, our results suggest that the putative increased CAN risk associated with anemia might be mediated by a correlated decrease in serum bilirubin levels.

Are Changes in Heart Rate Variability During Hypoglycemia Confounded by the Presence of Cardiovascular Autonomic Neuropathy in Patients with Diabetes?

We have recently shown how the combination of information from continuous glucose monitor (CGM) and heart rate variability (HRV) measurements can be used to construct an algorithm for prediction of hypoglycemia in both bedbound and active patients with type 1 diabetes (T1D). Questions remain on how cardiovascular autonomic neuropathy (CAN) influences these measurable changes. This study aims to examine if changes in HRV during hypoglycemia are confounded by the presence of CAN. Twenty-one adults (hereof 13 men) with T1D prone to hypoglycemia were recruited and monitored with CGM and a Holter device while they performed normal daily activities. CAN was diagnosed using two cardiac reflex tests: (1) deep breathing and (2) orthostatic hypotension and end organ symptoms. Early CAN was defined as the presence of one abnormal reflex test and severe CAN was defined as two abnormal tests or one abnormal test combined with symptoms of autonomic neuropathy. A total of 19 hypoglycemic and corresponding euglycemia periods were identified among the 21 patients. Eleven patients were diagnosed with CAN, hereof five with severe CAN. The HRV parameter low frequency (LF) was significantly (P = 0.029) reduced during hypoglycemia. Changes in LF during hypoglycemia were not different between patients with and without CAN, -0.64 versus -0.48 log(LF) (P = 0.74). Our data show that there are measurable changes in HRV during hypoglycemia, and present in both patients with and without CAN.