Cardiac Autonomic Neuropathy In Type Research Articles

Sleep duration is a significant predictor of cardiac autonomic neuropathy in type 2 diabetes mellitus

AimTo investigate the association between sleep quality outcomes and measures of cardiac autonomic function and to assess the predictive ability of sleep quality outcomes for cardiac autonomic neuropathy (CAN) in type 2 diabetes mellitus (T2DM). MethodsFifty patients with T2DM (age, 51.3±7.01years; glycemic control, 8.4±1.65%) completed the study. Patients were diagnosed for CAN using the standard clinical autonomic test battery and were also assessed for heart rate variability (HRV) under resting conditions. Sleep quality was examined using the Pittsburg Sleep Quality Index (PSQI). ResultsSleep duration, sleep onset latency, sleep efficiency, daytime dysfunction and global PSQI score showed significant correlations with measures of cardiac autonomic control (p<0.05). At an optimal cut-off of≤5.83h (area under the curve: 0.76, p=0.0003; sensitivity: 50%; specificity: 94.4%), sleep duration predicted occurrence of CAN (odds ratio, confidence interval: 0.18, 0.04–0.70; p=0.01) in T2DM after adjusting for various clinical confounders. ConclusionFindings of the present study suggest that subjective sleep outcomes such as sleep duration, sleep onset latency, sleep efficiency, daytime dysfunction and overall sleep quality are associated with the indices of cardiac autonomic function in T2DM. Moreover, short sleep duration may be considered a predictor in the occurrence of CAN in these patients. Considering the role of sleep in the pathophysiology of CAN, sleep should be routinely examined in patients with T2DM and appropriate therapeutic interventions should be implemented particularly in case of reduced sleep duration.

Prevalence of cardiac autonomic neuropathy in type 2 diabetic patients in rural part of Dharmapuri District

Prevalence of cardiac autonomic neuropathy in type 2 diabetic patients in rural part of Dharmapuri District

Heart rate variability in type 2 diabetes mellitus: A systematic review and meta-analysis

Background Cardiac autonomic neuropathy in type 2 diabetes mellitus (T2DM) patients is associated with high cardiovascular mortality. Heart rate variability (HRV) is the gold standard to measure cardiac autonomic neuropathy. We aimed to conduct a systematic review and meta-analysis to evaluate the impact of T2DM on HRV parameters. Methods Main databases were searched on 1st October 2017 using the keywords “diabetes” AND (“heart rate variability” OR “HRV”). Included articles reported HRV parameters in T2DM patients and healthy controls measured during 24 hours. Measurements of HRV retrieved were: RR intervals, standard deviation of RR intervals (SDNN), percentage of adjacent NN intervals differing by more than 50 milliseconds (pNN50), square root of the mean squared difference of successive RR intervals (RMSSD), total power, low frequency (LF), high frequency (HF) and LF/HF ratio. Results We included 1356 T2DM patients and 1576 healthy controls. T2DM patients had significantly (P Conclusions T2DM was associated with an overall decrease in the HRV of T2DM patients. Both sympathetic and parasympathetic activity were decreased, which can be explained by the deleterious effects of altered glucose metabolism on HRV, leading to cardiac autonomic neuropathy.

To study the impact of glycemic control over cardiac autonomic neuropathy in type 1 and type 2 diabetics patients using bedside tests at a tertiary care hospital

Background: Cardiac autonomic neuropathy a serious complication of diabetes and is often overlooked. It is associated with higher cardiovascular mortality and poor quality of life in diabetic individuals. The Glycemic control has been well established as the risk factor for all the diabetes related microvascular and macrovascular complications. This stresses importance of role of glycemic control over CAN in Type 1 and Type 2 Diabetics in order to stop further progression to advanced and irreversible stages. The objective was to study the impact of various demographic and other clinical factors over prevalence of CAN in type 1 and type 2 diabetic patients who are asymptomatic for CAN using bedside testsMethods: A case control comparative clinical study was undertaken comprising of 100 diabetic patients, both type 1 and type 2 with duration from 5-10 years and &gt;10 years. The tests which were performed are deep breathing test, heart rate response to standing, hand grip test, cold pressor test, BP response to standing. Depending on these tests, patients were categorised as patients with cardiac autonomic neuropathy and without cardiac autonomic neuropathy.Results: The prevalence of cardiac dysautonomia was 68%. Type 2 diabetics had higher prevalence of cardiac dysautonomia than type 1 diabetics (p=0.025). Significant correlation was observed between cardiac autonomic neuropathy and poor glycemic status (type 1 p&lt;0.001; type 2 p&lt;0.001). The mean HbA1c in patients with and without CAN in type 1DM was 9.16+0.81 and 7.21+0.56 and in type 2 DM was 9.15+1.72 and 7.15+0.53 respectively. Similarly, presence of other microvascular complications increased the prevalence of CAN in both types of diabetes mellitus.Conclusions: Cardiac autonomic neuropathy is a common complication in long standing diabetes. Present results suggest that glycemic status of the diabetics is undoubtedly an important factor for the onset of cardiac dysautonomia which in turn account for high prevalence of cardiac mortality in diabetic patients. All asymptomatic diabetic patients should be evaluated for the presence of autonomic neuropathy and glycemic status should be controlled to prevent the further progression of CAN.

Co-expression changes of lncRNAs and mRNAs in the cervical sympathetic ganglia in diabetic cardiac autonomic neuropathic rats.

Cardiac autonomic neuropathy in Type 2 diabetes (T2D) is often a devastating complication. Long non-coding RNAs (lncRNAs) have important effects on both normal development and disease pathogenesis. In this study, we explored the expression profiles of some lncRNAs involved in inflammation which may be co-expressed with messenger RNA (mRNA) in superior cervical and stellate ganglia after type 2 diabetic injuries. Total RNA isolated from 10 pairs of superior cervical and stellate ganglia in diabetic and normal male rats was hybridized to lncRNA arrays for detections. Pathway analysis indicated that the most significant gene ontology (GO) processes that were upregulated in diabetes were associated with immune response, cell migration, defense response, taxis, and chemotaxis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that most of the target genes of the lncRNAs were located in cytokine-cytokine receptor interactions, the chemokine signaling pathway and cell adhesion molecules, which were involved in T2D. Gene co-expression network construction showed that the co-expression network in the experimental rats consisted of 268 regulation edges among 105 lncRNAs and 11 mRNAs. Our studies demonstrated the co-expression profile of lncRNAs and mRNAs in diabetic cardiac autonomic ganglia, suggesting possible roles for multiple lncRNAs as potential targets for the development of therapeutic strategies or biomarkers for diabetic cardiac autonomic neuropathy. © 2016 Wiley Periodicals, Inc.

Potential Risk Factors for Cardiac Autonomic Neuropathy in Type 2 Diabetic Individuals in Rural Population of North Karnataka by Heart Rate Variability Analysis-a Cross Sectional Study

Cardiac Autonomic Neuropathy (CAN) is one of the major complications of Diabetes Mellitus (DM) since its presence is associated with worsening prognosis and poorer life quality. Heart Rate variability (HRV) which is early detector and a sensitive cardiac indicator can be used for early detection of complications among DM patients. The risk of developing autonomic dysfunction in DM depends on several factors but most of the studies have not reported it evidently. Hence this study was undertaken to determine the potential risk factors of CAN in T2DM individuals of rural population of north Karnataka. This study was carried out at three rural Primary Health Centers under administrative control of Jawaharlal Nehru Medical College, Belgaum, Karnataka, India. The associations of various risk factors with prevalence of CAN among diabetes individuals were assessed by chi-square tests analysis. P value < 0.05 was considered as statistically significant. Age, duration of diabetes, gender and diet were significantly associated with prevalence of CAN estimated by HRV analysis.

In vivo corneal confocal microscopy as a novel non-invasive tool to investigate cardiac autonomic neuropathy in Type 1 diabetes.

To investigate whether small nerve fibre degeneration detected using corneal confocal microscopy is associated with cardiac autonomic neuropathy in people with Type 1 diabetes. Thirty-six people with Type 1 diabetes and 20 age- and sex-matched healthy control subjects were enrolled. Tests to determine heart rate response to deep-breathing (expiratory-to-inspiratory ratio), heart rate response to lying-to-stand test (30:15 ratio) and blood pressure response to standing were performed to detect cardiac autonomic neuropathy. Corneal confocal microscopy was performed to assess: corneal nerve density and corneal nerve beadings; branching pattern; and nerve fibre tortuosity. Compared with control participants, participants with Type 1 diabetes had fewer (mean ± SD 45.4 ± 20.2 vs 92.0 ± 22.7 fibres/mm²; P < 0.001) and more tortuous corneal nerve fibres (20 participants with Type 1 diabetes vs four control participants had nerve tortuosity grade 2/3; P = 0.022) and fewer beadings (mean ± SD 15.1 ± 3.5 vs 20.6 ± 5.0; P < 0.001). Of the participants with Type 1 diabetes, 11 met the criteria for the diagnosis of cardiac autonomic neuropathy. Corneal nerve density was significantly lower in participants with cardiac autonomic neuropathy than in those without (mean ± SD 32.8 ± 16.4 vs 51.7 ± 18.9 fibres/mm²; P = 0.008). This difference remained significant after adjustment for age (P = 0.02), gender (P = 0.04), disease duration (P = 0.005), insulin requirement (P = 0.02) and neuropathy disability score (P = 0.04). This study suggests that corneal confocal microscopy could represent a new and non-invasive tool to investigate cardiac autonomic neuropathy in people with Type 1 diabetes. Larger studies are required to define the role of corneal confocal microscopy in the assessment of cardiac autonomic neuropathy.

Association between Brachial-Ankle pulse wave velocity and cardiac autonomic neuropathy in type 2 diabetes.

BackgroundCardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of vascular damages. The goal of this study was to investigate the relationship between BaPWV and CAN in T2DM.MethodsA total of 148 patients who had no apparent history of cardiovascular condition were enrolled consecutively in this study. The correlation between increased baPWV and CAN was analyzed. CAN was evaluated by five standard cardiovascular reflex tests (CARTs) according to the Ewing's protocol: 1) heart rate variation during deep breathing, 2) heart rate response to standing, 3) Valsalva maneuver, 4) postural systolic blood pressure (BP) change, 5) Sustained handgrip test. CAN was defined as the presence of at least two abnormal tests.ResultsThe mean age of patients was 59.8 ± 7.8 years. The mean duration of diabetes was 6.0(2.0-11.0) years. The mean baPWV was 1665.5(1482.0-1940.0) cm/sec. Subjects with CAN were older and had high BMI, baPWV compared with those without CAN. The proportion of patients with diabetic peripheral neuropathy was higher in subjects with CAN. After adjusting for other confounding risk factors, baPWV (odds ratio = 8.496, 95% CI: 1.216-59.348; P = 0.031) remained as independent risk factors for CAN. The number of abnormal CARTs increased gradually with increasing baPWV (correlation coefficient =0.255, p = 0.002).ConclusionIncreased baPWV was significantly correlated with CAN in patients with type 2 diabetes.

Diagnostic accuracy of heart‐rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy

Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation.

Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

BackgroundCardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.MethodsA total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.ResultsAlthough, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022).ConclusionsIn the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.

Natural progression of cardiac autonomic neuropathy in patients with type 1 diabetes: a four-year follow-up study

To determine the prevalence and clinical characteristics of cardiac autonomic neuropathy in type 1 diabetic patients who were followed up for 4 years to shed further light on the natural progression of cardiac autonomic neuropathy. It is a prospective cohort observational study, consisted of 57 patients who were originally studied using the standard tests proposed by Ewing and Clarke (1985). At two years follow up, 46 patients were reevaluated, 55 patients from the original study were reevaluated after another 2 years for the 3rd time using the same protocol. The control group comprised 30 age and sex matched healthy volunteers. McNemar test, ANOVA for repeated measurements, paired t test and unpaired t test were used for statistical analyses. The prevalence of established cardiac autonomic neuropathy (CAN) at the beginning was 14%. Q-Tc intervals were found to be significantly higher in patients with abnormal cardiovascular reflex (CVRs) in the 2nd examination (0.4±0.04 vs 0.5±0.05 sec, p=0.006). Eighteen patients showed deterioration of their CVRs test between 1st and 3rd examination. There was deterioration of their glycemic control guided by glycosylated hemoglobin (8.5±1.4 vs 9.9±1.5%, p=0.05*) and albumin/creatinine ratio (4.4±4.0 vs 28.2±28.0 mg/g creatinine, p=0.04). On the other hand, 12 patients showed regression of their CVRs test. Only their insulin dose showed significant decrease (1.8±1.3 vs 1.1±0.3 dose/kg, p=0.02). The prevalence of established CAN in diabetic patients is high at the beginning of the study. Glycosylated hemoglobin, systolic and diastolic blood pressure were significantly increased in diabetics with deterioration of their CAN. However, the dose of insulin was significantly decreased in diabetics with regression of their CAN.

Diastolic dysfunction is associated with cardiac autonomic neuropathy in type 2 diabetes

Purpose: Diabetic cardiomyopathy, characterised by LV diastolic dysfunction (DD), is linked to cardiac autonomic neuropathy (CAN) in type 1 diabetes. We sought to define the presence and importance of this association in type 2 diabetes (T2DM).Conclusions: CAN is independently associated with DD, and may have a role in the aetiology of subclinical myocardial dysfunction in T2DM.

Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients

Background: In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified. Objective: The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan. Methods: This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA 1c) and fasting plasma glucose obtained from monthly measurements over the previous 6 and 24 months were determined. Results: A total of 25 patients were enrolled (13 men, 12 women; mean [SD] age, 59.86 [8.28] years). Significant negative correlations between both ATP-WR and MIBG-WR and HbA 1c were found ( r = -0.52 [ P = 0.02] and −0.47 [ P = 0.03], respectively). Although no correlation was found between ATP-WR values and the early phase H/M ratio, a significant positive correlation was observed between ATP-WR and H/M ratio ( r = 0.54; P = 0.02). Conclusions: In the present study in Japanese diabetic patients without subjective signs of coronary artery disease and without abnormalities on ECG or echocardiography, ATP-WR, an indicator of myocardial blood flow, was correlated with myocardial sympathetic nerve dysfunction and 24-month glycemic control. However, sympathetic nerve dysfunction was not correlated with 24-month glycemic control.

The Role of Antioxidant Micronutrients in the Prevention of Diabetic Complications

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.

High prevalence and early onset of cardiac autonomic neuropathy among South Indian Type 2 diabetic patients with nephropathy

Objective: This study was conducted to assess the adverse effects of diabetic nephropathy on cardiovascular autonomic neuropathy (CAN) in South Indian Type 2 diabetic patients. Methods: Comparison was made between Type 2 diabetic patients with nephropathy (group 1, n=25), Type 2 diabetic patients without nephropathy (group 2, n=25) and non-diabetic, non-hypertensive control subjects ( n=20). All had a detailed clinical and biochemical work-up and cardiac assessment by ECG. Cardiac dysautonomia was assessed by a battery of five non-invasive autonomic function tests (ANF) as recommended by Ewing and Clarke [D.J. Ewing, B.F. Clarke, Diagnosis and Management of autonomic neuropathy. Br. Med. J. 285 (1982) 916–918]. Results: Group 1 patients showed a higher percentage of abnormal CAN function and a more severe form of CAN compared with patients in group 2. Group 1 patients showed early development of the abnormalities. They also had a higher prevalence of peripheral neuropathy compared with the patients without nephropathy. Conclusions: The present study showed that the presence of nephropathy was associated with the risk of cardiac autonomic neuropathy in Type 2 diabetic patients and it probably had an earlier onset also in them.