A Study of Cardiac Autonomic Neuropathy among Type-II Diabetic Patients

Background: Though very common, CAN is a least understood complication of diabetes which is often under diagnosed. In diabetes mellitus patients, CAN leads to silent myocardial infarction and sudden death. So by identifying CAN early, which is asymptomatic will help to delay or arrest its progression. AIM: To find out the prevalence and the associated risk factors of Cardiac autonomic neuropathy (CAN) among type-II Diabetes Mellitus patients in a tertiary care hospital. Materials & Methods: A total of 273 type-II diabetic participants were selected after taking into consideration of inclusion & exclusion criteria. The prevalence of CAN was assessed by ewings and clarkesnon invasive cardiac autonomic neuropathy reflex tests. The association of risk factors with the presence of CAN was analysed by using Pearson’s chi square test. Data were analysed by using SPSS 16. The accepted level of significance was set below 0.05 (P<0.05). Results: The prevalence of CAN among type-II diabetic patients in this study was found to be 34%. Prevalence of CAN increased in the participants with male gender, increased age, and increased BMI, increased duration of diabetes, poor glycaemic control,dyslipidimea, smokers and hypertension and it is statistically significant. Conclusion: In this study it is observed that the prevalence of CAN increased with old age, male Original Research Article Surendra et al.; JPRI, 33(41A): 345-352, 2021; Article no.JPRI.72996 346 gender, poor glycemic control, increased duration of diabetes, Dyslipidemia, higher BMI, Hypertension & smoking. So risk factors associated with the CAN be detected and treated at an early stage to further reduce morbidity and mortality.


INTRODUCTION
Diabetes is a metabolic disorder characterized by hyperglycemia that occurs either due to decreased insulin level or insulin resistance Diabetic Autonomic Neuropathy [1] can involve the entire autonomic nervous system (ANS). It is manifested by dysfunction [2] of one or more organ systems (e.g. cardiovascular, gastroint estinal, genitourinary, sudomotor, ocular) Though very common, CAN is a least understood complication of diabetes which is often under diagnosed. Not only does it affect the survival and quality of life in diabetics [3][4][5]. it is also a major source of increased cost in the diabetic care. Currently, a general consensus exists that CAN is an independent risk factor for cardiovascular events [6]. Its high mortality rate is related to cardiac arrhythmias, silent myocardial ischemia, sudden death, perioperative cardiovascular, and cardio respiratory instability [7]. The autonomic fibres innervating heart and blood vessels are affected in CAN and causes disturbances in cardiovascular dynamics [8] and anatomy [9]. It is recommended by several professional bodies [10-12] to perform subclinical assessment of CAN by utilizing CARTs as soon as T2DM is diagnosed. Ewing's CARTs are considered as Gold standard in CAN therefore, consistently been used for its subclinical assessment [13][14]. Hyperglycemia, obesity, dyslipidemia, hypertension, and smoking which are the modifiable risk factors are among the proposed risk factors for Cardiac autonomic neuropathy [15,[16][17][18][19][20][21]

MATERIALS AND METHODS
This cross-sectional study was conducted at department of General medicine OPD, Viswabharathi medical college from December 2019 to November 2020. 273 type-II DM patients with ≥ 3years of duration of both the sexes aged between 35-80 years were selected for this study by purposive sampling technique. Participants with other diseases associated with autonomic nervous system, Patients on drugs like sympathomimetics, and antiarrhythmics, patients with underlying cardiac illness, uncooperative and physically disabled patients were excluded from this study.

Study Protocol
A questionnaire which included sociodemographic details such as age, sex; anthropometric details such as height, weight; duration of diabetes, smoking & Hypertension history was administered to each patient.
Clinical and laboratory parameters such as BMI, Blood pressure, HbA1c, serum cholesterol, serum triglycerides were collected from each patient BMI: by dividing weight in kilograms by the square of height in meters BMI was calculated.
Blood pressure: It was measured with a standard mercury manometer and if their blood pressure values were >140/90 mmHg or they were taking any antihypertensive drugs were considered to have arterial hypertension. Estimation of serum cholesterol, serum triglycerides, HbA1c: After an overnight fasting, venous blood was drawn in the morning. Using automatic analyzer Serum cholesterol and serum tryglicerides were measured and Glycosylated hemoglobin (HbA1c) was measured by the high-performance liquid chromatography.

Ewings Cardiovascular Reflex Tests (CRT):
All the patients selected for study underwent Cardiovascular Reflex Tests (CRT) for evaluation of Cardiac autonomic neuropathy. Standard 12 lead ECG was taken and heart rate was measured by continuous ECG recording using lead II.
Instruments: 1. ECG instrument (CONTEC ECG300G) with paper speed of 25mm/sec 2. Diamond Sphygmomanometer BP instrument All five Ewing`s tests were performed as following for the detection of DCAN (diabetic cardiac autonomic neuropathy): I. Tests for assessing parasympathetic function 1) Heart rate response to deep breathing test: 2) Heart rate response to Valsalva maneuver 3) Heart rate response to standing II.. Tests for assessing sympathetic function: 1) Blood pressure response to sustained handgrip 2) Blood pressure response to standing The results were then categorized into one of the four groups Normal Early CAN -One of three parasympathetic tests abnormal or two border line Definite CAN-Two parasympathetic tests abnormal Severe CAN-Two parasympathetic tests abnormal + one or both sympathetic tests abnormal Statistical Analysis: Data analysis was done by using Software Package of Social Sciences (SPSS) trial version 16. Continuous data were analysed by using student unpaired t test. The association of risk factors with the prevalence of CAN was analysed by using Pearsons chi square test. The accepted level of significance was set below 0.05 (P<0.05).

RESULTS
A total of 273 type-II diabetes patients were included. Out of which 142 were males and 131 were females Prevalence of CAN based on Ewings tests criteria: Fig. 1 is showing the Prevalence of CAN based on Ewings tests criteria. The prevalence of CAN is 34% among typ-2 diabetes mellitus patients. Fig. 2 is showing the severity of CAN. Out of 93 T2DM participants with cardiac autonomic neuropathy, 36 (39%) individuals had 'early', 51 (55%) had 'definite' and 6 (6%) had 'advanced' Cardiac autonomic Neuropathy.

Severity of CAN:
Comparison of continuous variables between CAN & Non CAN participants was described in Table 1.
The association between various risk factors and prevalence of CAN was described in Table 2.

DISCUSSION
In the present study, the prevalence of CAN was found to be 34%. DAN [28] in their studies reported increasing age as a risk factor for the development of CAN among diabetes patients.

Fig. 2. Severity of CAN
Our study found that the male gender are more associated with CAN. This is in contrast with a study done by Sukl et al. [29] which reported that female gender as the risk factor for developing CAN. Bergstrom [35] in their study observed that the prevalence of CAN is associated with obesity.
Our study reported Hypertension as a risk factor for CAN. Similarly, Vincenza Spallone et al. [36] in their study found that the prevalence of CAN among diabetic patients is associated with an increase in Blood Pressure.
Our study reported smoking as a risk factor for CAN. Similarly Shai I et al. [37] reported that there is an increased prevalence of Cardiac Autonomic Dysfunction in individuals with smoking.

CONCLUSION
The prevalence of CAN in our study was found to be 34% and it is high. So these simple bedside tests are helpful in diagnosing the disease which enables to prevent its progression by appropriate interventions and it is concluded that risk factors are associated with the prevalence of CAN among type-II diabetes and therefore it highlights the importance of addressing not only glycaemic control but also modifiable risk factors like hypertension, dyslipidemia, smoking. So it is essential that risk factors associated with the progression and development of CAN be detected and treated at an early stage to further reduce morbidity and mortality.
In our study, the limitation of the study was the sample size which was not large enough to represent the whole population. so studies that include more subjects are required to confirm the findings of our study.