European Journal of Cardiovascular Medicine

The metabolic dysregulation associated with Type 2 Diabetes Mellitus (DM) leads to path changes in multiple organ systems, which are associated with high morbidity and impose a tremendous burden on the health care system, if they are not treated timely and adequately.

Among these, cardiovascular complications secondary to Type 2 DM, is one of the most common complications that increase mortality in these patients. The cardiovascular complications of DM can be classified into three groups; Atherosclerotic Coronary Artery Disease, Diabetic Cardiomyopathy and Cardiac Autonomic Neuropathy (CAN) [1]

CAN is a common form of Diabetic Autonomic Neuropathy (DAN), that causes abnormalities in heart rate control as well as central and peripheral vascular dynamics. CAN is also clinically important form of DAN, as it is associated with increased risk of mortality. [2]

In DM, CAN is ultimately the result of complex interactions among degree of glycemic control, disease duration, age-related neuronal attrition, and systolic and diastolic blood pressure. Hyperglycemia plays the key role in the activation of various biochemical pathways related to the metabolic and/or redox state of the cell, which, in concert with impaired nerve perfusion, contribute to the development and progression of diabetic neuropathies. Experimental data implicate a number of pathogenic pathways that may impact autonomic neuronal function in diabetes including: formation of advanced glycation end products, increased oxidative/nitrosative stress with increased free radical production, activation of the polyol and protein kinase C pathways, activation of polyADP ribosylation, and activation of genes involved in neuronal damage. [3,4].

Project Study Centre

The present project was conducted in the Shreeji Medical and Heart Hospital, Sidhpur, Gujarat.

Project Period

It was carried out from December, 2023 to May 2024, after getting approval by scientific committee.

Sample Size

Around 50 patients attending General Outpatient Department, Specialty clinic i.e. Diabetes and Geriatric Clinic were enrolled for the present project. Written consent was obtained from all the patients participating in the project after clearly explaining the project procedure in native language i.e. Gujarati.

Study Design

Cross sectional study

Sampling Method

Simple random sampling

Inclusion Criteria

• Patients with Type 2 Diabetes Mellitus who are on treatment.
• Newly diagnosed diabetics according to ADA (American Diabetes Association) criteria
• Patients of age between 30 and 65 years of both sexes.

Exclusion Criteria

• Type 2 DM Patients with age >65 years
• Type 2 DM Patients on drugs affecting the normal autonomic functions and causing Postural Hypotension
• Type 2 DM Patients with exposure to Alcohol
• Type 2 DM Patients with Documented ischemic heart disease
• Type 2 DM Patients with Hypertension and on antihypertensive drugs
• Type 2 DM Patients with congenital & acquired heart diseases & cardiac arrhythmias
• Type 2 DM Patients with Vitamin B12 deficiency
• Type 2 DM Patients with Impaired Renal Function/ Renal Failure
• Type 2 DM Patients with Parkinson & Parkinson plus syndromes.
• Type 2 DM Patients with liver diseases.

DATA COLLECTION

All patients who fulfilled the inclusion criteria were subjected to detailed history taking which includes other systemic autonomic dysfunction relevant history. Patients then subjected to detailed clinical examination which includes bedside tests for cardiovascular autonomic neuropathy. The bedside tests for assessing the autonomic nervous system were described by Ewing and Clarke. [5] Cardiovascular autonomic neuropathy was evaluated using Ewing Score based on cardiovascular autonomic function tests. [6]

1. A) TESTS FOR CARDIOVASCULAR AUTONOMIC FUNCTION [6] DONE IN THIS STUDY:
2. Heart Rate Response to Deep Breathing/ Deep breathing test
3. Heart Rate response to Valsalva Manoeuver
4. Heart Rate response to Standing - Postural Tachycardia Index (PTI or 30:15 Ratio)
5. Blood Pressure Response to Standing (Orthostatic test)
6. Blood Pressure Response to Sustained Handgrip

Grading of cardiovascular autonomic function

Results were classified into normal, borderline and abnormal (scores 0, 1, and 2 respectively).

An overall score of 0 or 1 were considered normal, whereas score of 2, 3 and 4 were considered borderlines and score ≥5 was judged abnormal autonomic function.

Table 1- Bedside Tests for Cardiac Autonomic Neuropathy diagnosis / Ewing’s Score Table [6]

1. B) Other Investigations

Other Biochemical Investigations based on individual patient profile were done

Statistical Analysis [7,8,9,10]

The data regarding history, clinical examination, routine and special investigations of study cases were entered in pretested Performa and observations were tabulated.

Chi square test was used to analyze the significance of Duration of Diabetes with CAN. p value which measures the probability was used at necessary places. p value of less than 0.05 was considered significant and p value less than 0.01 was considered highly significant. [7,8,9,10]

Statistical software namely SPSS 23.0 was used for the analysis of data and Microsoft word and excel have been used to generate graphs, tables and descriptive statistics.

The present study, ―Evaluation of Cardiac Autonomic Neuropathy in Type 2 Diabetes Mellitus patients attending Diabetes Clinic comprised of fifty cases of type 2 diabetes mellitus that were attending our diabetes clinic at Shreeji Medical and Heart Hospital and were assessed for Cardiac Autonomic Neuropathy. The data of the present study was tabulated as under.

We have divided the patients in three groups according to their duration of Diabetes mellitus. (Table 2)

Table 2. Distribution of Patients according to Duration of Diabetes Mellitus:

(n = 50)

In the present study, seventeen (34 %) cases were having DM for less than five years they were enrolled as group 1, seventeen (34 %) cases were having DM for five to ten years who were in group 2 and sixteen (32%) patients had DM for more than ten years who are in Group 3.

Mean age of patients in group 1 is 50.2 + 9.71, in group 2 it is 51.2 + 8.75 while mean age in group 3 is 56.3 + 4.1.(Table 3)

Table 3. Mean age of patients according to Duration of DM

(n=50)

Out of total fifty study cases, thirty-two (64%) males and eighteen (36%) were females.

Male to Female ratio was 1.77:1. (Table 4)

Table 4. Gender wise Distribution of Study Cases

(n=50)

The CAN score derived from HR Response to Deep Breathing, HR response to Valsalva Manoeuver, HR response to Standing, BP Response to Standing and BP Response to Sustained Handgrip. (Table 1)

An overall score of ‘0’ or ‘1’ was considered normal, score 2, 3, 4 were considered borderlines and score ≥5 was judged abnormal autonomic function. In our study out of 50 patients 20 (15 male, 5 female) patients were normal – no cardiac autonomic neuropathy with CAN score of 0 or 1, mean age of those patients was 51.65 while 12 (5 male, 7 female) patients had CAN score 2, 3 or 4 and they were considered as having borderline cardiac autonomic neuropathy with mean age of 52 years.

We found total 18 (12 male, 6 female) patients who had CAN score > 5 and they were considered as having definite cardiac autonomic neuropathy, mean age of them being  52.7 years.(Table 5, Graph 1)

So, prevalence of CAN in our study is 60 % of which 36 % had definite CAN and 24% had evidence of borderline/early CAN.

Table 5 Distribution of Patients according to CAN Score (n=50)

Graph 1 Distribution of Patients according to CAN Score

In our study from seventeen patients whose duration of DM was less than 5 years, eleven (64.7%) patients had no CAN, four (23.5%) patients had borderline CAN and only two (11.7%) patients had definite CAN.

From seventeen patients whose duration of DM was between 5 to 10 years, seven (41.2%) patients had no CAN, six (35.3%) patients had borderline CAN and only four (23.5%) patients had definite CAN. Out of sixteen patients whose duration of DM was more than 10 years, two (12.5%) patients had no CAN, two (12.5%) patients had borderline CAN and twelve (75%) patients had definite CAN. To find correlation between development of Can and duration of DM, we applied Chi Square test to our data. Chi square value is 17.67 and p value is 0.0014 which is < 0.01 which is highly significant so in our study Development of CAN is strongly related to Duration of DM. (Table 6, Graph 2)

Table 6. Distribution of Patients According to CAN Score and Duration of Diabetes (n=50)

Graph 2 Distribution of Patients according to CAN Score and duration of Diabetes

The present study ―Evaluation of Cardiac Autonomic Neuropathy in Type 2 Diabetes Mellitus patients attending Diabetes Clinic comprised of fifty cases of Type 2 Diabetes Mellitus. This study was conducted from December 2023 to May 2024 at Shreeji Medical and Heart Hospital, Sidhpur - Patan, Gujarat.

We studied the cases for development of cardiac Autonomic neuropathy and its correlation with duration of DM and with ECG changes marked by Corrected QT interval. In present study we observed that Cardiac autonomic Neuropathy is more common in patients of DM.

Prevalence of CAN in Type 2 Diabetes Mellitus:

In our study we found prevalence of CAN is 60 % of which 36 % had definite CAN and 24% had evidence of borderline/early CAN. Pappachan JM et al [1] studied the prevalence the CAN amongst 100 patients of DM type 1 and 2, in south India. He diagnosed CAN by Ewing’s methodology and autonomic function test according to Ewing. The prevalence of CAN was 60% which is comparable to the results obtained in this study. Various other authors quoted prevalence of CAN in T2DM as following (Table 7). The results of which are comparable to result obtained in our study.

Table 7. Prevalence of CAN in type 2 Diabetes mellitus in various studies

Mean Age of CAN patients:

In our study Mean age in the definite cardiac autonomic neuropathy group was 52.7 years, 52 years in borderline CAN patients and that in the diabetic group without autonomic neuropathy was 51.6 years. This is comparable with Study done by Pillai JN [12] et al in which mean age for neuropathy patients was more than that of patients without neuropathy.

CAN and Duration of Diabetes mellitus:

In our study we have obtained statistically significant correlation between duration of diabetes mellitus and development of cardiac autonomic neuropathy with chi square value 17.67 and p value of 0.0014 (highly significant if p value is < 0.01). From total 16 patients who had definite CAN, 75% patients had T2DM since more than 10 years. This observation is comparable with study done by Toyry JP et al [14] and Pappachan JM et al [1] in which prevalence of cardiac neuropathy was higher with increased duration of DM.

Limitations

Newer procedures for assessing autonomic functions like the computer aided power spectral analysis of heart-rate variability could not be done in our project study due to lack of resources and cost. Newer techniques can help to diagnose CAN at earliest.

In our study out of fifty patients 40% patients were with no cardiac autonomic neuropathy, while 24% had borderline cardiac autonomic neuropathy and 36% had definite cardiac autonomic neuropathy. Prevalence of CAN in our study is 60 % of which 36 % had definite CAN and 24% had evidence of borderline/early CAN. Mean age of neuropathy patients was more than that of patients without neuropathy.The Prevalence of CAN in study patients increased with increased duration of DM. There is strong stastically significant correlation between Development of CAN and Duration of DM.

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