Cardiac Autonomic Neuropathy In Type Research Articles

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

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

FREQUENCY OF CARDIAC AUTONOMIC NEUROPATHY IN TYPE 2 DIABETES MELLITUS PATIENTS PRESENTING TO KHYBER TEACHING HOSPITAL PESHAWAR

This study aimed to determine the frequency of cardiac autonomic neuropathy in patients with type 2 diabetes. A cross-sectional study was conducted at the Department of Medicine, Khyber Teaching Hospital Peshawar, Pakistan, from June 2022 to June 2023. The study included 285 individuals aged 40-60 diagnosed with type 2 diabetes for at least 5 to 10 years. The study aimed to evaluate the frequency of cardiac autonomic neuropathy in type 2 diabetics. Chi-square was applied for statistical analysis with a significance level of p≤0.05. Of 285 type 2 diabetic patients, 199 (69.82%) were male, and 86 (30.18%) were female. 26.31% of the participants were diagnosed with cardiac autonomic neuropathy, of which 26.67% were male and 73.33% were female. This difference was statistically significant. 37.35% of the patients with cardiac autonomic neuropathy were smokers, while 62.65% were non-smokers. All the patients with CAN were either overweight or obese. This study found that prolonged diabetes is directly related to the development of cardiac autonomic neuropathy, and there was a statistically significant association between diabetes and gender, as well as smoking.

Risk Factors Associated with Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus

Background: Cardiac Autonomic Neuropathy (CAN) is one of Type 1 Diabetes Mellitus complications with a high mortality rate. This condition might occur right after T1DM is diagnosed but is often asymptomatic. Cardiac Autonomic Reflex Tests (CART’s) are one of the gold standard, non-invasive diagnostic with high sensitivity used for screening but rarely used in children. Some risk factors are associated with CAN, and one of them is poor glycemic Control. Objective: To delineate risk factors associated with Cardiac Autonomic Neuropathy in children with Type 1 Diabetes Mellitus at Dr. M Jamil Padang Hospital. Methods: A diagnostic test study was performed on children aged under 18 years old who came to the outpatient pediatric endocrinology clinic of M. Djamil Hospital or Pediatric Ward between February till August 2022 whom caregivers agreed to sign in the informed consent and follow instructions to do one of CART’s maneuver called Heart Beat to Deep Breathing with ECG and draw a level HbA1C as Glycemic Control. Secondary data was collected from medical records. Data analysis was performed with a 2x2 table using a computer program Result: 34 samples were collected, with mean age T1DM 13,14±2,75 years and mean age at onset 10,4±2,65 years. CAN was diagnosed in 13 (38,2%) T1DM subjects and there was no signification between onset at age (p=1,0), duration of illness (p=0,653), and Glycemic control (p=0,132). Conclusion: No significant correlation was found between risk factors associated with Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus. Keywords: CART’s, Cardiac Autonomic Neuropathy, Type 1 Diabetes Mellitus

Interest of the SUDOSCAN in the screening of cardiac autonomic neuropathy in type 2 diabetics

Introduction: Cardiac autonomic neuropathy (CAN) is one of the first complications of type 2 diabetes (T2DM) and a silent cause of cardiovascular morbidity and mortality. SUDOSCAN, a digital chronoamperometric analysis device, has appeared in recent years and allows a rapid and non-invasive quantitative assessment of sudomotor function, which will allow the measurement of sympathetic cholinergic function in the assessment of CAN by reflecting the state of the autonomic nervous system. The main purpose of the present study is to evaluate the usefulness of SUDOSCAN in the detection of cardiac autonomic neuropathy in type 2 diabetic patients. Patients and methods: In this study we recruited 85 patients with type 2 diabetes. The study data were collected by questionnaire, clinical examination and SUDOSCAN. Results: The 85 patients had a mean age of 58.32 ± 10.89 years, with a large female predominance, and a sex ratio of 0.28. 67% of our patients had diabetes for less than 10 years. The SUDOSCAN measurement noted 54.1% with a moderate risk of having CAN, 45.9% with a low risk, and a zero percentage with a high risk of having CAN. Conclusion: The risk score for cardiac autonomic neuropathy assessed by SUDOSCAN, and its ease of use and interpretation, make it a good screening test for cardiac autonomic neuropathy in patients with type 2 diabetes.

Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus.

Background Cardiovascular autonomic neuropathy (CAN), an important form of DAN is caused by the impairment of the autonomic nerve fibers that innervate the heart and blood vessels and leads to abnormalities in cardiovascular dynamics. The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV). Objective The objective is to assess the effect of ramipril 2.5mg once daily on cardiac autonomic neuropathyin type II DM patients as an add-on to a standard antidiabetic regimen for a duration of 12 months. Materials and methods A prospective, open-label,randomized, parallel-group study was conducted on type II DM with autonomic dysfunction. Patients in Group A received tablet ramipril 2.5mg daily along with the standard antidiabetic regimen which consist of Tab Metformin 500mg twice a day and Tab Vildagliptin 50mg twice a day and group B received only the standard antidiabetic regimen for 12 months. Results Among 26 patients with CAN, 18 patients completed the study. After one year in group A, Delta HR value increases from 9.77±1.71 to 21.44±8.44 and the E:I ratio (ratio of the longest R-R interval during expiration and shortest R-R intervalduring inspiration) improved from 1.23±0.35 to 1.29±0.23 signifying significant improvement in parasympathetic tone. Results of the postural test showed significant improvement in SBP.Analysis of HRV by time domain method showed that the standard deviation of RR (SDRR) interval and Standard deviation of differences between adjacent RR interval (SDSD)value increased significantly in group A.Analysis of HRV frequency domain indices showed that LFP:HFP ratio improved after treatment in ramipril group indicating improvement in sympatho-vagal balance. Conclusion Ramipril improves parasympathetic component more as compared to sympathetic component of DCAN in type II DM. Ramipril could be a promising option having favorable long-term outcomes in diabetic patients especially when treatment begins at subclinical stage.

Association between plasma apolipoprotein M and cardiac autonomic neuropathy in type 1 diabetes

AimDiabetes may lead to severe complications e.g. cardiac autonomic neuropathy (CAN) characterized by an increased risk of cardiovascular mortality. CAN is diagnosed by a decreased heart rate viability (HRV). Sphingosine-1-Phosphate (S1P) carried by the HDL-associated apolipoprotein M (apoM) is linked to a reduction in the heart rate, and treatment with an S1P-agonist increases HRV. The present study aimed to investigate if plasma apoM was associated with an increased risk of CAN. MethodsThe study includes 278 individuals with Type 1 Diabetes recruited from Steno Diabetes Center in Copenhagen from 2010 to 2012. ResultsA change of 0.1 µM plasma apoM was associated with the diagnosis of CAN (Odds ratio: 1.11 (1.02; 1.21), p = 0.013). ApoM plasma levels were also positively associated with CAN when adjusted for age and gender (Odds ratio: 1.11 (1.02; 1.21), p = 0.013) as well as lipids, beta-blockers, blood pressure, and alcohol (Odds ratio: 1.14 (1.04; 1.26), p = 0.005) and Hbga1c and time with diabetes (Odds ratio: 1.13 (1.02; 1.25), p = 0.01). Plasma apoM was also associated with a significantly lower SDNN as well as high frequency power in all adjusted models. ConclusionIncreased plasma apoM was associated with an increased risk of CAN as well as a significant reduction in HRV indices. This could represent changes in parasympathetic activity, but, further studies are needed to also explore additional molecular alterations behind such observations.

Ventricular depolarization and repolarization variability in children with type 1 diabetes mellitus.

Arrhythmias can be seen as a sign of cardiac autonomic neuropathy in type 1 diabetes mellitus. We aimed to evaluate pulmonary artery pressure, ventricular depolarization and repolarization variability in children with type 1 diabetes mellitus. We investigated 78 children with type 1 diabetes mellitus (mean age 11.6 ± 3.6 years) and 68 age-gender matched healthy children as control group. All type 1 diabetes mellitus patients were divided into three subgroups according to glycated hemoglobin (HbA1c) levels and the duration of disease. Electrocardiogram and transthoracic echocardiograms were performed on both groups. In patients with type 1 diabetes mellitus, there was an elongation in P, Pd, PR, QTc, QTd, QTcd, JT, JTc, JTd, Tp-Te and Tp-Te/QT, Tp-Te/QTc, Tp-Te/JT, Tp-Te/JTc ratios were higher (P < 0.05). In patients with type 1 diabetes mellitus, pulmonary artery pressure was higher than control group (P = 0.001). Prolongation of QTc, thickness of left ventricle end-diastolic diameter and left ventricle posterior wall diameter were higher in the HbA1c ≥9% subgroup. When adjusted for age there was no significant correlation between left ventricle parameters and HbA1c. Atrial conduction delay and impairment of ventricular repolarization were significantly high and there was a predisposition for the development of pulmonary artery hypertension in children with type 1 diabetes mellitus. Poor glycemic control was not a risk factor for propensity of left ventricle hypertrophy and left ventricle dysfunction.

Detection of cardiac autonomic neuropathy in type II diabetic patients using heart rate recovery

Background Cardiac autonomic neuropathy is one of the most insidious complications of diabetes mellitus. It can be detected by abnormality in heart rate recovery, which is defined as decline in heart rate within the first few minutes following a graded exercise stress test. Aim To detect cardiac autonomic neuropathy in type II diabetic patients using heart rate recovery. Patients and methods This study included 45 individuals, 30 diabetic patients in case group and 15 healthy individuals as a control. All participants underwent history taking, clinical examination, laboratory investigations (FBS, PPBS, HbA1c, kidney function test and liver enzymes), comprehensive transthoracic echocardiographic examination, 24 h Holter monitor and exercise ECG test to assess heart rate recovery. Results 30 diabetic patients (7 male and 23 females, with mean age 40±3.5 years) and 15 healthy individuals (4 males and 11 females with mean age 36±5.8 years) participated in this study. Cases group had significant increase in FBS, PPBS, HbA1c and serum creatinine compared to control group. Patients had significant decrease in PNN50, SDNN, LF and HF in the 24 h Holter monitoring as well as significant delay in heart rate recovery at 1st and 2nd minutes compared to control group. Glycemic control and duration of diabetes were the most predictors to abnormal heart rate recovery. Conclusion Heart rate recovery derived from exercise ECG test could be considered as an easy, low cost and widely available tool for detection of cardiac autonomic neuropathy.

Role of Brain Derived Neurotrophic Factor and Swimming Exercise in Cardiac Autonomic Neuropathy in Type 2 Diabetes Rat Model

Cardiac Autonomic Neuropathy (CAN) is a major chronic complications of DMII. Clinical investigations have revealed that uncontrolled DM II is frequently associated with lower levels of BDNF. This study assessed whether diminished BDNF level is the reason of CAN caused by DM II and if swimming aerobic exercise can increase BDNF level to ameliorate that CAN . Sixty rats were divided into six groups. Group I; Normal (N), Group 2; BDNF blocker, Group 3; DM II, Group 4; DM II + BDNF, Group 5; DM II + Swimming exercise and Group 6; DM II + Swimming exercise + BDNF blocker. Induction of DM II was done by intraperitoneal injection of 180 mg/kg of Nicotinamide 30 minutes before injection of 50 mg/kg Streptstozin. Swimming exercise began with a 1-week adaptation with gradual increase of swimming duration until reaching 1h swimming/day at the end of the 1st week. Then, a 7-weeks training program with 5 days/week swimming was followed. The duration of the experiment was 8 weeks during which the following parameters were measured: body weight, random blood glucose “RBG” level, plasma insulin level, heart rate “HR”, systolic blood pressure “SBP”, heart rate variability “HRV”, baroreflex sensitivity “BRS”, vascular sympathetic tone “VST” and plasma BDNF. Results revealed that BDNF significantly improved RBG level, HRV, VMT and BRS. Swimming exercise significantly increases plasma BDNF level and also improved CAN. Conclusively, BDNF can be used as a treatment regimen for CAN. Also swimming exercise has great therapeutic effect on CAN maybe by producing BDNF.

Risk of cardiac autonomic neuropathy in latent autoimmune diabetes in adults is similar to type 1 diabetes and lower compared to type 2 diabetes: A cross-sectional study.

Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life-threatening complication of diabetes, also varies depending on diabetes type. In this cross-sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p<0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25-1.20, p-value: 0.13) and 2.71 (95% CI: 1.21-6.06, p-value 0.015) respectively. Smoking (adj OR 3.09, 95% CI: 1.40-6.82, p-value: 0.005), HDL cholesterol (adj OR 0.29, 95% CI: 0.09-0.93, p-value: 0.037) and hypertension (adj OR 2.11, 95% CI: 1.05-4.24, p-value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors.

Stratification of the Type 2 Diabetes Mellitus Based on Heart Rate Variability Parameters in Elderly Women at Rest

Cardiac autonomic neuropathy in type 2 diabetes mellitus (T2DM) patients is frequent and associated with high cardiovascular mortality. The purpose of the present study was to stratify the T2DM using a logistic model based on parameters derived from heart rate variability (HRV). This study was designed as a cross-sectional study of consisted of thirty elderly women subjects 60 to 70 yrs of age with diagnosed with T2DM (N = 15) and healthy (N = 15). All subjects were instructed to lie in the supine position for 5 min at rest while breathing normally with a heart rate monitor Polar RS810 working at a sampling rate of 1000 Hz was used to record RR intervals (RRi). The HRV analysis in the time domain was performed to obtain the classical parameters pNN50, SDNN, RMSSD and MeanRRi and, subsequently, re-sampling procedure to bootstrapping based on 1000 samples. The model for predicting T2DM was obtained by backward stepwise multivariate logistic regression assuming as independent variable MeanRRi. This model presented 0.80 positive predictive value, 0.73 negative predictive value and 0.76 total accuracy. In conclusion, the use of the proposed MeanRRi parameter measured at rest seems to be able to stratify the T2DM in elderly women. The benefits of HRV monitoring the severity of T2DM should be potential as a reliable and non-invasive.

Vitamin C ameliorated cardiac autonomic neuropathy in type 2 diabetic rats.

BACKGROUNDVitamin C (VC) is a common antioxidant with cell protection potentials. However, its possible protective effect on cardiac autonomic nerves from diabetic induced insults is yet to be explored.AIMTo investigate the effects of VC on diabetic cardiac autonomic neuropathy.METHODSThirty male Wistar rats were equally grouped into control, diabetic and diabetic + VC. Type 2 diabetes was induced with fructose diet and alloxan. VC (1 g/kg) was administered for 4 wk via oral canula. Blood pressure and heart rate were measured non-invasively using tail flick blood pressure monitor. Spectral analysis of heart rate variability (HRV) was used to assess cardiac autonomic neuropathy. Blood was collected from the ocular sinus for biochemical analysis. Urethane (1 g/kg-ip) was used for anaesthesia prior to HRV and cervical dislocation to harvest hearts. Intracardiac autonomic nerve was assessed using tyrosine hydroxylase immunohistochemistry on fixed heart sections.RESULTSResults were analysed using ANOVA at α0.05. Unlike VC and control groups, diabetic rats showed significantly (P < 0.0001) reduced HRV, increased heart-rate and blood pressure, initial increase in cardiac tyrosine hydroxylase activities at week-2 and sparse activity at week-4 of diabetes. Furthermore, apolipoprotein B, Oxidative stress and inflammatory markers were significantly (P < 0.01) reduced in VC treated rats.CONCLUSIONVC possesses cardio-autonomic nerve protective potential and ameliorates the symptoms of cardiac autonomic neuropathy in type 2 diabetes. The possible mechanisms via which VC exert these effects may be via downregulation of oxidative stress, inflammation and apolipoprotein B.

Use of the Polar H10 cardiofrequencemeter and Ewing's autonomic function tests in the screening of cardiac autonomic neuropathy in type 1 diabetes mellitus in Yaoundé

Cardiac autonomic neuropathy (CAN) is one of the chronic complications of diabetes that can be detected by studying spontaneous or induced changes in heart rate and blood pressure. To investigate and characterize CAN in a group of young type 1 diabetics patients. This was a cross sectional study carrying out in Yaounde Central Hospital. We successively realize a clinical examination, rest electrocardiogram, 3 min heart rate variability measure and five Ewing's functions tests (heart rate response, orthostatic blood pressure, vasalva test, control ventilation and forearm isometric contraction) with a POLAR H10 cardiofrequencemeter. Quantitative variables were express by the mean and his standard deviation; qualitative variables were expressed using frequencies. Sixty type 1 diabetics patients (37 males and 33 females) with a sex ratio of 1.6. The mean age was 19,6 ± 4.3 years, with diabetes of duration 5.9 ± 5.1 year, a mean BMI of 21.7 ± 2.9 kg/m 2 and a mean HbA1c of 9.1 ± 3.1%. Prevalence of CAN was 86.7%. The mean heart rate at rest was 82.9 ± 14.7bpm, a systolic blood pressure of 116.8 ± 18.9 mmHg, diastolic blood pressure of 70.4 ± 11.8 mmHg. The orthostatic blood pressure response was abnormal, restrict, normal respectively for 1 (1.7%), 5 (8.3%) and 54 (90%) subjects. The orthostatic response of the heart rate was abnormal for 20% of subjects and restrict for 10%. 28.3% of subjects had an abnormal Valsalva test. We found an abnormal forearm isometric contraction for 90% of subjects. The HRV index for parasympathetic activity were down low for 93.3% while index for orthosympathetic activity were down low for 90% of subjects. CAN is frequent in type 1 diabetes patients. The five Ewing and Clarke tests are replicable in clinical practice with the H10 polar cardiofrequencemeter. Thus, developing a single standard and universal consensus for the interpretation of these tests is important for a better screening of CAN.

Identification and performance of multiple clinical and laboratorial risk factors for diagnosis of cardiac autonomic neuropathy in type 1 diabetes patients.

The incidence of cardiac autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D) is frequently underestimated. Individuals with T1D and CAN have an increased mortality risk, mainly from cardiovascular causes. The objectives of the present study were to assess the clinical and laboratory characteristics associated with CAN in patients with T1D and verify the ability of multiple clinical factors to help identify patients with this condition. 102 patients with T1D were evaluated for CAN using standardized cardiovascular reflex testing. Clinical characteristics were used to compute a numerical score for CAN diagnosis and a ROC curve elaborated for assessment of the best cutoff to predict CAN. This score was then applied to the second sample of 120 patients. The sensitivity, specificity, and positive and negative predictive values were calculated. Prevalence of CAN was around 35% in the first sample of patients and just below 20% in the second sample. Hypertension, total cholesterol, triglycerides, postprandial sweating, diastolic blood pressure, abnormal right and left 10g monofilament, retinopathy, and nephropathy were considered independent predictors of CAN. The CAN-score cut-off was 16.88. This yielded a sensitivity of 50%, specificity 73.8%, positive predictive value 22.9%, and negative predictive value 90.5%. The use of a subset of clinical and laboratory characteristics can be more accessible than the cardiac reflex tests and more accurate than a single isolated characteristic.

Short term optimization of glycaemic control using insulin improves sympatho-vagal tone activities in patients with type 2 diabetes

IntroductionDiabetic cardiac autonomic neuropathy (CAN) is potentially life threatening and its severity might further be aggravated by poor glycaemic control. A decrease in Heart rate variability (HRV) is the earliest finding of CAN even at the sub clinical stage. While intensive glycaemic control prevents the development of CAN in patients with type 1 diabetes, it is not known whether the intensification of glycaemic control using insulin would improve cardiovascular autonomic functions in type 2 diabetes patients. This study aimed to determine the short term effects of optimizing glycaemic control using insulin on the HRV in type 2 diabetes patients. MethodsWe conducted a single arm open label clinical trial. Participants were poorly controlled non-insulin treated type 2 diabetes mellitus patients (HbA1c ≥ 7%). The intervention lasted 60 days and consisted in the intensification of glycaemic control through the initiation of a basal plus insulin regimen with titration of insulin to protocol defined glycaemic targets which were; fasting glycaemia: 0.70–1.30 g/L and post prandial glycaemia <1.80 g/L. Long term HRV measurement was done using a 24-h ambulatory electrocardiographic (ECG) recording on day 0 and day 60. Wilcoxon signed rank test was used to compare differences in HRV parameters before and after the intervention. ResultsA total of 29 (14 males and 15 females) consenting type 2 diabetes mellitus patients without clinical signs of CAN were enrolled and allocated to intervention (14 males and 15 females). The median age was 52 [43–59] years, and duration of diabetes 3.0 [0.6–6.7] years. The intervention induced a reduction in HbA1c from 10.1 [9.1–11.9]% to 6.7 [5.9–6.9]% (p < 0.001) without severe hypoglycaemic events. Concerning HRV parameters, there was a significant improvement in markers of the parasympathetic tone (PNN50: 5.7 [3.6–10.3]% to 8.1 [3.1–16.9]%, p = 0.008) and sympathetic tone (SDNN: 102.01 [90.45–111.05] ms to 122.40 [91.70–135.95] ms, p = 0.01). ConclusionThe optimization of glycaemic control using a basal plus insulin regimen while inducing a significant reduction in glycated hemoglobin, significantly improves 24-h ambulatory ECG derived sympathetic and parasympathetic activities. This suggests that tight glycaemic control using insulin may revert cardiac autonomic neuropathy in type 2 diabetes mellitus patients.

The haptoglobin 2-2 genotype is associated with cardiac autonomic neuropathy in type 1 diabetes: the RETRO HDLc study.

The haptoglobin (Hp) 2-2 genotype has been shown to increase the risk of coronary artery disease, kidney dysfunction and mortality from cardiovascular and renal causes in type 1 diabetes (T1D). Similar associations, however, have not been observed in those without diabetes. As cardiac autonomic neuropathy (CAN) is a cardiovascular disease risk factor, we assessed the presence of an association between the Hp 2-2 genotype and CAN. The study included 216 individuals with childhood-onset T1D and 200 individuals with normal glucose tolerance (NGT) of similar age and gender distribution to their counterparts with T1D. CAN was assessed using an electrocardiogram as an abnormal, age-specific, heart rate response to deep breathing. Multivariable logistic regression models were used to assess the association between the Hp 2-2 genotype and CAN. Compared with NGT, participants with T1D had a similar proportion of Hp 2-2 carriers (41.5% vs. 32.0%, p = 0.05) but a greater CAN prevalence (28.2% vs. 5.0%, p < 0.0001). In multivariable logistic regression models, those carrying the Hp 2-2 genotype had significantly higher odds of CAN compared with Hp 1-1 or Hp 2-1 carriers (OR = 2.27, p = 0.01). The presence of T1D (OR = 4.20, p = 0.0003), hypertension (OR = 2.08, p = 0.03), eGFR (OR = 0.98, p = 0.01) and WBC count (OR = 1.21, p = 0.02) were also associated with CAN. There was no T1D by Hp interaction (p = 0.92), although in stratified analyses, the Hp-CAN association was significant only in T1D. The Hp 2-2 genotype was independently associated with greater odds of CAN in T1D though no definitive conclusions could be made in NGT.

Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes.

The present study aimed to examine association between inflammatory and endothelial function biomarkers and indices of cardiac autonomic control in T2DM patients. 50 T2DM patients were recruited for this study. For cardiac autonomic function, cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV) analysis was performed. Blood samples were collected for evaluating inflammatory and endothelial function biomarkers. Multivariable linear regression analysis adjusted for diabetes duration, glycemic control, waist circumference, hypertension, dyslipidemia, metformin, and statins was performed to examine the association between the biomarkers and cardiac autonomic function parameters. Interleukin-6 was inversely related to total power (p= .009) and low frequency power (p= .04). Interleukin-18 and high sensitivity C-reactive protein inversely correlated with measures of cardiac vagal control (p < .05). Both nitric oxide and endothelial nitric oxide synthase were positively linked with cardiac vagal control indices (p < .05) whereas endothelin-1 did not show any independent association with cardiac autonomic function parameters. Biomarkers of inflammation and endothelial function are associated with measures of cardiac vagal control and global HRV which suggest that there is some pathophysiological link between subclinical inflammation, endothelial dysfunction and cardiac autonomic dysfunction in T2DM.

Prevalence of cardiac autonomic neuropathy in type 2 diabetes mellitus and its correlation with other microvascular complications in South Indian population

Background: In individuals with type 2 diabetes mellitus (T2DM) the presence of Cardiac autonomic neuropathy (CAN) increases the risk of severe hypoglycaemia, cardiac arrhythmias, silent myocardial ischemia and stroke. It is also associated with increased perioperative morbidity and mortality, even with minor surgeries in these patients. The present study was conducted to assess the prevalence of CAN in T2DM patients and to investigate any possible association between CAN and micro vascular complications.Methods: 102 T2DM patients between the age of 30 years and 70 years, who attended outpatient department of Institute of Diabetology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai, Tamil Nadu were included. All the selected patients underwent laboratory investigations, biothesiometry, fundus examination, and CAN assessment by CANS analyser.Results: A slight female preponderance was noted in the study, though it was statistically insignificant. Out of 102 patients, prevalence of CAN dysfunction was found in 82 (80.39%) of T2DM patients. No significant association of CAN was noted with duration of diabetes (p=0.772), HbA1c (p=0.827) and nephropathy (p=0.524). However, peripheral neuropathy (p=0.006) and retinopathy (p=0.03) were found to be significantly associated with CAN in T2DM patients.Conclusions: Prevalence of CAN in asymptomatic South Indian T2DM population was found to be 80.39%, with equal sex distribution and was most common in the 51- 60 years age group. Diabetic neuropathy and retinopathy were the most significant microvascular complications predictive of the incidence of CAN in T2DM patients.

Diagnostic performance of resting and post-exercise heart rate variability for detecting cardiac autonomic neuropathy in type 2 diabetes mellitus.

Post-exercise recovery phase is associated with clustering of various cardiovascular events and, therefore, monitoring of cardiac autonomic control via heart rate variability (HRV) during this phase may allow identification of autonomic alterations that are not evident under resting conditions in type 2 diabetes mellitus (T2DM) patients. To investigate and compare the diagnostic performance of resting and post-exercise HRV for detecting cardiac autonomic neuropathy (CAN) in T2DM patients. Forty-two T2DM patients were categorized as CAN-positive and CAN-negative based on standard cardiovascular autonomic reflex tests (CARTs). Short-term resting and post-exercise HRV after a graded exercise test were evaluated for each participant. Diagnostic performance of both resting and post-exercise HRV measures was computed using standard statistical procedures. Diagnostic testing yielded superior diagnostic performance of post-exercise HRV than resting HRV measures. Root mean square of successive differences (RMSSD) between adjacent R-R intervals (p = 0.01), percentage of consecutive N-N intervals that vary by >50 ms (pNN50) (p = 0.03) and total power (TP) (p = 0.01) were significantly better diagnostic indicators of CAN under post-exercise conditions than at rest. Predictive ability of these post-exercise HRV measures for CAN was maintained after adjusting various clinical confounders to cardiac autonomic function. Post-exercise HRV measures such as TP, RMSSD and pNN50 were found to be more accurate diagnostic tests for detecting CAN than resting HRV. Hence, monitoring of the HRV measures proposed here during exercise testing protocols may provide important diagnostic information regarding CAN in T2DM.

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.