Geetha. P1*, Bharathi. D1, Deepa. N1, Gopi. G1, Shamshath Begum1, Devi. T2
1Faculty of Pharmacy, Sree Balaji Medical Collage and Hospital Campus, BIHER, Chromepet, Chennai.
2Chettinad School of Pharmaceutical Sciences, Chettinad Academy of Research and Education,
Chettinad Hospital and Research Institute, Kelambakkam, Chennai.
*Corresponding Author E-mail: lgeethapharma@gmail.com
ABSTRACT:
One of the major side effects of diabetes mellitus (DM) that raises the rates of morbidity and death is diabetic cardiovascular autonomic neuropathy (CAN). As an antioxidant, alpha lipoic acid shows promise in lowering autonomic neuropathy. 138 participants with type 2 DM participated in the prospective observational research. Autonomic function, biochemical markers, and baseline demographics were measured. Patients receiving anti-diabetic medicine and oral dose of 200 mg of alpha lipoic acid for complications were observed for three months. Prior to and following the three-month period, the autonomic nerve system index (ANS) score was assessed. The ANS index score significantly decreased, and the neuropathy was found to have improved. There was statistical significance in the results. The study's conclusions demonstrated alpha lipoic acid's possible advantages in CAN management.
KEYWORDS: Cardiovascular Autonomic Neuropathy, Alpha-Lipoic Acid, Diabetes.
INTRODUCTION:
Diabetes is the cause for 1.5 million demises every year, and there are over 422 million diabetics in low- and middle-income nations worldwide.1 The rate and incidence of diabetes has been steadily rising during the past several decades.2 Cardiovascular autonomic neuropathy(CAN) denotes to the impairment to the autonomic nerve that to supply nerves to the heart and blood vessels, leading to anomalies in heart rate control and blood flow pattern, making it one of the significant consequences of diabetes most commonly ignored.2-5
CAN is well-defined as the damage of autonomic regulation of the circulatory process in the presence of insulin resistance syndrome once rulling out the potential causes.6 Varoius cardiovascular autonomic reflex tests (CARTs) are typically recommended to document CAN.7 Complications of Diabetes mellitus (DM) such as cardiac autonomic neuropathy are underdiagnosed and are higher mortality and morbidity rates. In type 2 DM, CAN is present in between 31 and 73% of cases, with a reported 2% yearly incidence.8,9 Pathogenetic therapy for CAN includes the following: therapies of myocardial metabolic conditions; preclusion then management of thrombosis; treatment of hyperlipidaemia; antioxidants, particularly alpha-lipoic acid (ALA); vasodilators; lipid-soluble B1 vitamin (benfotiamine);omega-3 polyunsaturated fatty acids; medicine of concurrent illness (arrhythmias, hypertension, heart failure); and lifestyle modification.10,11 In addition to protecting peripheral neurons from lipid peroxidation and scavenging free radicals directly, ALA also recycles other natural antioxidants and boosts catalase and superoxide dismutase (SOD), which can lower endoneurial blood flow and nerve transmission.12 Alpha lipoic acid's impact on CAN in persons with insulin resistance syndrome was the main focus of our investigation.
Our investigation was a prospective observational study carried out at Chennai, India's private tertiary care hospital. Since November 2022 to April 2023, 138 type 2 DM patients who were receiving outpatient care were participated in the study. Patients, age above 18, those with DM type 2, co-morbid conditions, and diabetic complications who were receiving regular anti-diabetic medications as well as treatments for diabetic complications that contained alpha lipoic acid were recruited. Our study excluded individuals with DM type 1, pregnant and breastfeeding women, patients with chronic illnesses, and patients who were under the age of 18. Every participant provided their prior consent form, and the research was carry through in accordance with the standards set by the ethical committee of our institute. (ECR/288/Indt/TN/2018/RR-21/027). Body mass index (BMI), blood pressure, and resting heart rate were all determined as part of a comprehensive medical examination given to each patient. All patients were given an overnight fast before having blood drawn the next morning. The lipid profile fasting state (triglycerides/TG /LDL, high-density lipoprotein/HDL, and low-density lipoprotein) was estimated by an automatic analyzer. High-performance liquid chromatography was used to measure glycosylated haemoglobin (HbA1c).
Microalbumin levels in urine allowed for the detection of diabetic nephropathy due to anomalies in urine excretion. It was calculated using the immunoassay technique. Diabetes-related nerve degeneration results in the painful condition known as diabetic peripheral neuropathy. Biothesiometer instrument was utilized to test for Vibration perception threshold (VPT) in order to detect initial peripheral neuropathy in the feet measured in volts. Blood flow to the lower limbs was evaluated by the Ankle Brachial Index (ABI) test. For the arteries in the inferior limbs remained more susceptible to atherosclerosis. The ABPI, which measures peripheral arterial disease, is the ratio of ankle to upper arm blood pressure. The condition known as CAN is another one of diabetes' many complications. This causes a painless myocardial infarction, also known as a silent heart attack. With the aid of Dyansys (ANSiscope), an examination was shown to conclude whether diabetes was affecting the sympathetic and parasympathetic heart nerves. The individuals have cardiac autonomic neuropathy, which was detected. Aimed at a period of 3 months, the patients were prescribed with anti-diabetic medications, medications for diabetic complications, and 200mg of alpha lipoic acid. The CAN number were noted both at the initial and three months afterwards.
Statistical analysis was carried out by Version 23 of IBM-SPSS. Summary data were displayed as median (min and max) or mean SD. The Chi-square test was performed to determine the statistical significance of the difference between the initial and end of 3 months therapy in order to conclude the effectiveness of alpha lipoic acid, a p-value of 0.05 was deemed significant statistically.
According to our study, 138 individuals who were enrolled and completed the time frame, an average age of 55.12 ± 12.49 yrs was determined. In terms of the patients' gender, there were 64 female patients and 74 male patients. The average of 11.04±7.33 yrs was the duration of diabetes. The enrolled patients BMI was estimated as 26.61 ± 4.82 kg/m2. The FBS and PPBS value was evaluated as 155.1 ± 54.1 and 205.5 ± 74.1 mg/dl correspondingly. The initial measurement of HbA1C was 8.5± 2.1%. Table 1 represents the demographics and baseline biochemical investigations of the recruited subjects. In this research ANS index were compared among at the baseline and at next 3 months of the management with alpha lipoic acid (200mg). Further, there was a substantial reduction of ANS index levels when compared between baseline vs 3 months. The results were shown in Table 2.
|
Parameters |
Values (Mean±SD) |
|
Demographics |
|
|
Duration of Diabetes Mellitus |
11.04±7.33 years |
|
Age |
55.12±12.49 years |
|
Gender |
Male: 74 Female: 64 |
|
BMI |
26.61±4.82kg/m2 |
|
Biochemical profiles |
|
|
Fasting Blood Sugar |
145.08±49.31mg/dl |
|
Post-Prandial Blood Sugar |
199.36±61.53mg/dl |
|
HbA1C |
8.71±5.41% |
|
Blood pressure-Systole |
135.26±17.34mm/hg |
|
Blood pressure-Diastole |
79.86±10.71mm/hg |
|
Total Cholesterol |
144.58+28.97mg/dl |
|
Triglycerides |
130.96+36.02mg/dl |
|
Low Density Lipoprotein |
83.42+18.97mg/dl |
|
Very Low-Density Lipoprotein |
26.74+7.09mg/dl |
|
Serum Creatinine |
0.87±0.158mg/dl |
|
Estimated Glomerular Filtration Rate (eGFR) |
94±20mg/dl |
|
Urea for Microalbuminuria |
24.74 ± 5.23 mg/dl |
|
C-Reactive Protein-Baseline |
1.4 ± 0.58 mg/l |
|
ANS index at baseline |
34 ± 13.5 |
|
ANS index after 3 months |
24 ± 10.17 |
Table 2: Assessments of the enrolled subjects ANS index before and after treatment with alpha lipoic acid
|
ANS index |
No of patients (Before treatment) |
No of patients (After treatment) |
p-value (chi-square test) |
|
Healthy <11% |
2 |
9 |
< 0.00001. |
|
Early 11–20% |
18 |
56 |
|
|
Late 21–50% |
97 |
70 |
|
|
Advanced 51–60% |
16 |
3 |
|
|
Most-advanced 61-100% |
5 |
0 |
The ANS index score was used to assess the impact of ALA both before and after the standard course of treatment and after taking 200mg of ALA. We discovered that our findings were statistically significant. The ANS index score improved, and patients in the late and advanced ANS index categories moved back to the prior score category, indicating that alpha lipoic acid treatment is effective for type 2 DM patients. Excess hyperglycemia caused a rise in mitochondrial manufacturing of ROS, which harmed the micro vessels that supplied blood to the peripheral neurons. Antioxidant ALA enhances blood flow to peripheral nerves, encourages nerve regeneration, and lowers inflammation and the generation of oxygen free radicals. Our study's findings were supported by a randomized double blind placebo control that included several dosages of ALA. At the conclusion of the trial, the total symptom score was evaluated, and substantial results were identified.13 Another multicenter trial by Lee et al. evaluated heart rate variability for CAN using 600 mg/day dose by mouth for the first twelve weeks of ALA and 1200 mg/day for the continuing twelve weeks. The study's findings lacked statistical significance.14 ALADIN I and ALADIN II investigations demonstrated that ALA improved nerve conduction.15,16 Beat-to-beat Vectocardiogram were used in a study to investigate the benefits of ALA and reveal its favorable effects.17
CONCLUSION:
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Received on 03.02.2025 Revised on 13.03.2025 Accepted on 16.04.2025 Published on 08.07.2025 Available online from July 12, 2025 Asian J. Pharm. Tech. 2025; 15(3):286-288. DOI: 10.52711/2231-5713.2025.00043 ©Asian Pharma Press All Right Reserved
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