Effect of Yoga on Endothelial Function and Vascular Aging in Individuals with Type-2 Diabetes (Yoga V-AgE): A Randomized Controlled Trial

OBJECTIVES OF THE STUDY

Primary Objective: To determine if yoga practice improves endothelial function and prevent or improves atherosclerosis in individuals with type-2 diabetes.

Secondary objectives: (1) To determine the preventive effects of yoga on early vascular aging and vascular complications in individuals with type-2 diabetes. (2) To compare the effects of different components of yoga (Yogasanas, pranayama, meditation) on vascular system in patients with type-2 diabetes. (3) To determine the underlying mechanism of yoga on vascular health and diabetes.

METHODOLOGY

Study population, design & protocol: A four-arm, parallel-treatment, prospective randomized open blinded end-point (PROBE) study will be conducted on a total of 248 (62 in each arm) patients with type-2 diabetes mellitus (T2DM) with age ranging between 30-65 years. Volunteers will be screened at Visit 1-3 during which glycemic status, three consecutive BP recordings (on three consecutive days) and clinical history will be taken. At visit 4, baseline investigation followed by randomization and allocation of subjects to either intervention arms (study groups) or control arm will be done. Post-intervention investigation will be made at Visit 5. Persons handling data analysis will be kept blinded (single blinded).

**Selection criteria:**Patients aged between 30-65 years with T2DM will be included for the study. Diabetes subjects with atherosclerosis are also eligible for the study. Subjects with SBP ˃ 139 mmHg and DBP ˃ 89, subjects with any CV disease and other significant diseases (other than atherosclerosis) or clinically significant abnormal laboratory values during screening will be excluded from the study.

Randomization: The eligible subjects will be allocated for either intervention arms or control arm using the computer generated random number.

Intervention:

**Arm-1:**Study group-1 (n=62)-Subjects of this group will practice Yogasanas (with dietary modification) for one hour/day for 5 days in a week for 3 months under the supervision of trained yoga instructor, along with their standard care.

**Arm-2:**Study group-2 (n=62)-Subjects of this group will practice Pranayama and Meditation (with dietary modification) for one hour/day for 5 days in a week for 3 months under the supervision of trained yoga instructor, along with their standard care.

**Arm-3:**Study group-3 (n=62)-Subjects of this group will practice integrated yoga (Yogasanas, pranayama, meditation and dietary modification) for one hour/day for 5 days in a week for 3 months under the supervision of trained yoga instructor, along with their standard care.

**Arm-4:Control group (n=62)-**Subjects of this group will receive only standard care.

Outcomes of the study

Primary outcomes**:**Changes in the atherosclerosis markers and endothelial function

**Secondary outcomes:**Changes in the vascular aging markers, autonomic function, cardiovascular hemodynamics, oxidative stress and inflammatory markers.

**Data analysis:**Data will be presented as mean ± SD with confidence intervals. Level of significance: Statistical significance will be established at p< 0.05. Mean difference with confidence intervals will be calculated. Distribution of data will be verified. Difference between four groups will be analyzed using ANNOVA. Paired-t test will be applied to find the difference within group, if the data is uniformly distributed. Non-parametric test will be used to analyze non-uniform data. Analysis of Covariance (ANCOVA) will be applied to find the differences in the post-intervention values between study and control groups while controlling the pre-test values.

Summary of the proposed research

Cardiovascular complications are the most common and leading cause of death among diabetic patients. A prominent cardiovascular complication of diabetes is accelerated atherosclerosis and early vascular aging. Endothelial injury and dysfunction occur as initial event in the pathogenesis of atherosclerosis, arterial stiffness and other cardiovascular complications including hypertension. Endothelial dysfunction is a major mediator of diabetic vascular complications. Therefore, preventing endothelial damage and treating endothelial dysfunction is a primary focus in the prevention of vascular and cardiac complications associated with diabetes. Although studies have shown that yoga improves glycemic status and risk profiles in persons with diabetes, there are profound gaps in knowledge about the effects of yoga on endothelial function, vascular aging and central haemodynamics in persons with T2DM. Therefore, we aimed to determine if yoga can induce beneficial changes in the vascular endothelial system and attenuate early vascular aging and atherosclerosis in individuals with T2DM.