1. What data in particular will be shared?
   Response - All of the individual participant data collected during the trial, after de-identification.
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   Response -  Analytic Code
   Response - None of the above
   
   
3. Who will be able to view these files?
   Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
   


4. For what types of analyses will this data be available?
   Response - Any purpose.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [grreddy836@gmail.com].
   


6. For how long will this data be available start date provided 24-01-2025 and end date provided 24-01-2027?
   Response - Immediately following publication. No end date.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

“Screening Patients with Type 2 Diabetes Mellitus for Carotid Artery Disease in a Rural Tertiary Care Hospital”

1. Title of the Study

Screening the Patients of Type 2 Diabetes Mellitus for Carotid Artery Disease: A Study from a Rural Tertiary Care Hospital

2. Introduction

Type 2 Diabetes Mellitus (T2DM) is a well-recognized risk factor for cardiovascular diseases, including carotid artery disease (CAD). CAD, characterized by atherosclerotic plaque formation in the carotid arteries, significantly increases the risk of stroke. Rural populations are often underserved in healthcare, leading to late detection and management of such conditions. Early detection of CAD in T2DM patients can aid in timely interventions, reducing the burden of complications and improving outcomes. This study aims to screen T2DM patients for CAD and assess its prevalence in a rural tertiary care setting, where resources are limited, and healthcare access is a challenge.

3. Background and Significance

Cardiovascular diseases are the leading cause of mortality worldwide, and their burden is disproportionately high in patients with T2DM. Studies have shown that individuals with diabetes have a two- to fourfold increased risk of developing atherosclerosis, which can lead to carotid artery disease. CAD is a major contributor to stroke, one of the most devastating complications of diabetes, often resulting in significant morbidity and mortality.

The rural population faces unique healthcare challenges, including limited access to specialized diagnostic tools, inadequate healthcare infrastructure, and lower awareness of preventive measures. These factors contribute to delayed diagnosis and treatment of conditions such as CAD. Moreover, rural patients often have a higher prevalence of uncontrolled diabetes and associated comorbidities due to poor healthcare access and socioeconomic constraints.

Carotid Doppler ultrasonography is a non-invasive, reliable, and cost-effective diagnostic tool for detecting CAD. However, its utilization in rural healthcare settings remains limited due to a lack of resources and trained personnel. By conducting this study, we aim to bridge this gap by identifying the prevalence and risk factors of CAD in T2DM patients and demonstrating the feasibility of integrating routine CAD screening into existing healthcare practices in rural areas. This effort aligns with global health priorities to reduce the burden of non-communicable diseases and improve healthcare equity.

4. Literature Review

Several studies have highlighted the interplay between Type 2 Diabetes Mellitus and carotid artery disease. Research has consistently demonstrated that chronic hyperglycaemia accelerates the process of atherosclerosis by promoting endothelial dysfunction, oxidative stress, and inflammation. A study by Gonzalez et al. (2018) reported that T2DM patients are 1.5 times more likely to develop carotid plaques compared to non-diabetic individuals. Additionally, increased intimal-medial thickness (IMT), an early marker of atherosclerosis, is frequently observed in diabetic populations, particularly among those with poor glycaemic control.

Regional studies focusing on rural populations have revealed alarming trends of undiagnosed and unmanaged CAD in T2DM patients. For instance, Kumar et al. (2020) demonstrated a prevalence of 35% for subclinical carotid atherosclerosis among diabetic patients in resource-limited settings. However, despite this evidence, routine screening for CAD remains underutilized in rural areas due to economic and infrastructural constraints.

The significance of early detection and intervention is underscored by the findings of Patel et al. (2019), which showed that early management of carotid atherosclerosis in diabetic patients led to a 20% reduction in stroke incidence over a five-year period. These findings emphasize the urgent need for systematic screening protocols tailored to rural healthcare contexts.

3. Objectives

1. Primary Objective: To determine the prevalence of carotid artery disease in patients with Type 2 Diabetes Mellitus attending a rural tertiary care hospital.
2. Secondary Objectives:
• To assess the association between clinical and demographic factors (e.g., age, gender, duration of diabetes, HbA1c levels) and the presence of CAD.
• To evaluate the utility of non-invasive screening tools, such as carotid Doppler ultrasonography, in detecting CAD.
• To identify potential barriers to CAD screening and propose strategies to overcome them in resource-limited settings.

 6. Hypothesis

Primary Hypothesis: The prevalence of carotid artery disease (CAD) in Type 2 Diabetes Mellitus (T2DM) patients in rural settings is significantly higher than in the general population and is associated with poor glycemic control and other modifiable cardiovascular risk factors.

Secondary Hypothesis: Routine non-invasive screening, such as carotid Doppler ultrasonography, can effectively identify subclinical CAD in T2DM patients, facilitating timely interventions and reducing complications in resource-limited rural settings.

7. Preliminary Studies

Preliminary studies conducted at the rural tertiary care hospital indicate a high prevalence of uncontrolled diabetes among patients attending the outpatient clinic. A retrospective review of medical records over the past two years revealed that approximately 40% of T2DM patients had evidence of cardiovascular complications, including hypertension and dyslipidemia. While specific data on carotid artery disease prevalence was not available, anecdotal evidence from clinicians suggests that a significant proportion of patients presenting with cerebrovascular events have underlying diabetes and atherosclerosis.

Additionally, a pilot study involving 50 T2DM patients screened using carotid Doppler ultrasonography found that 28% had increased intimal-medial thickness (IMT), while 12% had plaques causing more than 50% stenosis. These findings underscore the need for systematic screening and early intervention strategies to address the burden of CAD in this population. The current study builds on these findings by employing a larger sample size and more robust methodology to provide comprehensive data on the prevalence and risk factors of CAD in rural T2DM patients.

4. Methodology

4.1 Study Design

A cross-sectional, observational study.

4.2 Study Setting

The study will be conducted in the outpatient and inpatient departments of a rural tertiary care hospital that primarily caters to underserved populations. The hospital’s geographical location, demographic details, and the proportion of diabetic patients attending the facility will be described in detail in the study.

4.3 Study Population

Patients diagnosed with Type 2 Diabetes Mellitus attending the outpatient or inpatient departments of the hospital. The study will aim to include a diverse group of patients from varying socio-economic backgrounds and levels of healthcare access.

4.4 Inclusion Criteria

• Patients aged 18 years and above.
• Diagnosed cases of Type 2 Diabetes Mellitus for at least 1 year.
• Patients providing informed consent for participation.

4.5 Exclusion Criteria

• Patients with known carotid artery disease.
• History of cerebrovascular accidents or transient ischemic attacks.
• Patients with significant renal dysfunction (eGFR < 30 mL/min/1.73 m²).
• Pregnant or lactating women.
• Patients unable to undergo carotid Doppler ultrasonography due to medical or logistical reasons.

4.6 Sample Size Calculation

SAMPLE SIZE: 151

FORMULA USED:

Z = 1.96

P =11% = 0.11

d= 5% = 0.05

n = 1.96² *0.11*(1-0.11)

                     0.05²

           n= 150.43

             = 151 Patients needed in study.

4.7 Sampling Technique

Systematic random sampling will be used to recruit eligible patients. Every patient meeting the inclusion criteria will be included in the study to minimize selection bias.

4.8 Study Duration

The study will be conducted over a period of 12 months. This includes 9 months of patient recruitment and data collection, followed by 3 months of data analysis and reporting.

5. Data Collection

5.1 Patient Assessment

• Detailed clinical history, including:
• Duration of diabetes.
• Smoking history and alcohol use.
• Family history of cardiovascular diseases.
• Presence of comorbidities such as hypertension and dyslipidemia.
• Anthropometric measurements:
• Height, weight, body mass index (BMI), and waist-hip ratio.
• Blood pressure measurements:
• Taken using a calibrated sphygmomanometer; three readings will be averaged for accuracy.

5.2 Laboratory Investigations

• Fasting and postprandial blood glucose levels.
• Glycated hemoglobin (HbA1c).
• Lipid profile, including total cholesterol, LDL, HDL, and triglycerides.
• Renal function tests, including serum creatinine and estimated glomerular filtration rate (eGFR).
• Inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), will be considered if feasible.

5.3 Imaging Modalities

• Carotid Doppler ultrasonography will be performed by a trained radiologist to assess:
• Intimal-medial thickness (IMT).
• Presence and severity of atherosclerotic plaques.
• Degree of stenosis.
• Standardized protocols will be followed to ensure reproducibility and reliability of results.

6. Quality Control Measures

• All equipment used for anthropometric measurements and blood pressure recording will be calibrated regularly.
• Standard operating procedures (SOPs) will be developed and followed for laboratory tests and imaging techniques.
• Training sessions will be conducted for the research team to ensure uniform data collection.
• Inter-observer variability in carotid Doppler ultrasonography will be minimized by ensuring that all scans are performed by a single trained radiologist or reviewed by a second radiologist for validation.
• Periodic internal audits will be conducted to monitor data accuracy and adherence to the protocol.

7. Data Analysis

• Descriptive statistics will be used to summarize demographic and clinical data.
• Prevalence of CAD will be calculated with a 95% confidence interval.
• Chi-square tests, independent t-tests, and logistic regression analysis will be used to determine associations between risk factors and CAD.
• Subgroup analysis will be conducted to assess differences based on gender, age groups, and glycaemic control (HbA1c levels).
• A p-value < 0.05 will be considered statistically significant.

8. Follow-up Mechanisms for Positive Findings

• Participants found to have significant carotid artery disease will receive immediate counselling on lifestyle modifications and medical management.
• Referrals will be made to cardiologists or neurologists for advanced care if necessary.
• A structured follow-up schedule will be designed for these patients, including:
• Quarterly assessments for glycemic control and cardiovascular risk factor management.
• Repeat carotid Doppler ultrasonography after 6–12 months to monitor disease progression.
• Patient navigators will be employed to ensure adherence to follow-up visits and treatment plans.

9. Ethical Considerations

• Approval will be obtained from the Institutional Ethics Committee (IEC) before commencing the study.
• Written informed consent will be obtained from all participants, with detailed information on study procedures, risks, and benefits.
• Confidentiality of patient data will be strictly maintained, with access limited to the research team.
• Participants found to have significant carotid artery disease will be counselled and referred for appropriate management.

10. Expected Outcomes

• Determination of CAD prevalence in T2DM patients in a rural tertiary care setting.
• Identification of key demographic, clinical, and biochemical risk factors associated with CAD.
• Insights into the feasibility of routine CAD screening in diabetic patients using non-invasive methods in resource-limited settings.
• Recommendations for integrating CAD screening into routine diabetic care in rural healthcare facilities.

11. Limitations

• Single-center study, limiting the generalizability of findings.
• Cross-sectional design precludes establishing causality.
• Potential challenges in patient compliance and follow-up, particularly in rural settings.
• Variability in operator performance for carotid Doppler ultrasonography.

12. Dissemination of Findings

The study results will be presented at national and international conferences and published in peer-reviewed journals to contribute to the body of knowledge on CAD screening in T2DM patients in rural healthcare settings. Additionally, findings will be shared with local healthcare providers and policymakers to promote the implementation of evidence-based screening protocols.