The World Health Organization (WHO) approximates that more than 400 million individuals worldwide are affected by diabetes, with projections indicating a rise to 592 million by the year 2035(1). Diabetes, a chronic metabolic disorder characterized by elevated blood glucose levels, poses significant risks to multiple organ systems, including the heart, blood vessels, eyes, kidneys, and nerves. Type 2 diabetes, typically occurring in adults, arises when the body develops insulin resistance or fails to produce sufficient insulin. Over the past three decades, the prevalence of type 2 diabetes has surged worldwide across diverse socioeconomic settings. Type 1 diabetes, previously referred to as juvenile or insulin-dependent diabetes, involves the pancreas producing minimal or no insulin autonomously. For individuals managing diabetes, access to affordable treatment, notably insulin, is indispensable for their well-being. A globally endorsed objective aims to halt the escalation of diabetes and obesity by the year 2025(1,2). Type 2 diabetes mellitus represents a significant global health challenge, with an estimated prevalence of 366 million in 2011, a figure expected to surge by 51% to reach 552 million by 2030. India mirrors this global trajectory, with a prevalence of 60 million in 2011, projected to escalate by 63% to reach a total of 97.8 million by the year 2030(1,3). This poses a significant threat to public health. Inadequately controlled diabetes can result in severe and potentially fatal complications affecting the heart, liver, stomach, kidneys, muscles, as well as vascular and peripheral nerves. According to the Global Report on Diabetes, diabetic complications may include heart attacks, strokes, blindness, renal failure, and lower limb amputations. However, diabetes can be effectively managed through a range of therapeutic interventions(1,4). Acupuncture, an ancient form of alternative medicine with a history spanning over 2500 years, is widely practiced worldwide. It involves the insertion of needles at specific points on the body, known as acupoints, along meridians or energy pathways. Stimulation of these acupoints is believed to produce therapeutic effects that target specific areas or functions of the body(5). More than 2,000 years ago, the ancient Chinese medical text, Yellow Emperor's Classics of Internal Medicine, first documented the significance of the ear in relation to the human body. It highlighted the ear's connection to various internal organs and emphasized that all meridians converge at the ear. Recognizing the importance of standardizing acupoint locations, the Chinese Association of Acupuncture and Moxibustion was entrusted by the World Health Organization (WHO) with the task of establishing consistent acupoint locations. This standardization aimed to facilitate uniformity and coherence in the study and exchange of ideas within the field of acupuncture(6). Stimulation of the ear acupoint MA-IC 3 Endocrine is facilitated by the anterior vagus rami auricularis, a branch of the vagus nerve responsible for innervating internal organs. Through acupuncture-mediated stimulation of this nerve, there's a potential activation of pancreatic beta cells, leading to insulin secretion. Acupuncture may also modulate the sympathetic or parasympathetic nervous systems. Stimulation of parasympathetic nerves via cholinergic fibers prompts the release of acetylcholine, which stimulates insulin secretion and influences pancreatic beta cell receptors. Additionally, this process triggers the secretion of proteins involved in insulin signaling, such as insulin-like growth factor. These mechanisms could underlie the observed increase in insulin action induced by acupuncture, potentially enhancing insulin sensitivity while reducing insulin resistance(7). Previous research has predominantly focused on evaluating the efficacy of acupuncture in achieving glycemic control, employing various acupoints. For instance, a study conducted by R. Kumar et al. in 2017 observed a notable decrease in Random Blood Glucose levels within 30 minutes following acupuncture needling at CV-12 acupoint in patients with Type 2 Diabetes Mellitus (T2DM)(3). According to national diabetes guidelines, the current standard of care for assessing glycemic control in hospital settings and adjusting insulin therapy relies on bedside point-of-care capillary glucose testing (POC). This method involves glucose testing before meals and at bedtime. However, POC testing has limitations, as it does not offer a complete 24-hour glycemic profile assessment and may miss asymptomatic or nocturnal hypoglycemia. Consequently, the utilization of Continuous Glucose Monitoring (CGM) has seen a significant expansion in recent years. CGM provides the advantage of continuously measuring interstitial glucose levels every 5-15 minutes, offering a comprehensive 24-hour glycemic profile assessment and enabling better detection of nocturnal and asymptomatic hypoglycemia. Additionally, CGM allows for pattern recognition after treatment. Large-scale studies utilizing CGM have demonstrated its efficacy in facilitating and enhancing diabetes care in ambulatory patients treated with insulin, regardless of diabetes type(8). In a study conducted by Sergio Vencio et al. in 2021, the impact of acupuncture on glycemic control in individuals with Type 2 Diabetes was investigated using Continuous Glucose Monitoring (CGM). The findings revealed a decrease in mean glucose levels and enhancements in overall glycemic control throughout the 14-day monitoring period among participants receiving acupuncture treatment(9). As of now, the therapeutic effects of auricular acupuncture on blood glucose levels in individuals with Type 2 Diabetes Mellitus have not been investigated on acupoints like Pancreas point, Endocrine point, and Point Zero. Therefore, this study represents a pioneering effort in investigating the time latency for such effects. The study will utilize the FreeStyle Libre Pro system developed by Abbott Diabetes Care to monitor blood glucose levels. This system is a flash glucose monitoring system that provides a comprehensive record of an individual's glucose levels, trends, and patterns over up to 14 days. Similar to continuous glucose monitoring, flash glucose monitoring relies on measuring glucose concentrations in the interstitial fluid rather than directly in the blood(10). As a result, this study has the potential to be groundbreaking in the field of acupuncture research.

AIM AND OBJECTIVES: 

Aim:

To Explore the Efficacy of Auricular Acupuncture Points Pancreas, Endocrine, and Point Zero in Managing Type 2 Diabetes Mellitus Patients.

Objectives:

Primary Objective: To investigate the efficacy of auricular acupuncture targeting the pancreas point, endocrine point, and point zero in improving glycaemic control, as measured by changes in mean glucose levels assessed via Freestyle Libre Pro continuous glucose monitoring, in individuals with Type 2 Diabetes Mellitus.  To investigate the change in mean glucose levels, as assessed by Freestyle Libre Pro continuous glucose monitoring, following auricular acupuncture targeting the pancreas point, endocrine point, and point zero, stratified by age groups (e.g., < 50>65 years old), in individuals diagnosed with Type 2 Diabetes Mellitus.

Secondary Objectives:

To evaluate the effect of auricular acupuncture targeting the pancreas point, endocrine point, and point zero on insulin sensitivity, as measured by changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores(11), in individuals with Type 2 Diabetes Mellitus. 

Participating Units:

1. International Institute of Yoga and Naturopathy Medical Sciences, Chengalpattu (Outpatient Department):

• This unit serves as the primary site for patient recruitment, intervention administration, and data collection. Located in Chengalpattu, it offers outpatient services specializing in yoga, naturopathy, acupuncture, and energy medicine.
• The Outpatient Department (OPD) of the International Institute of Yoga and Naturopathy Medical Sciences is responsible for identifying eligible participants, explaining the study protocol, obtaining informed consent, and conducting acupuncture interventions.
• Additionally, this unit will manage the follow-up visits, monitor participants' progress, and oversee data collection procedures throughout the study period.
• The OPD ensures adherence to the study protocol, ethical standards, and safety measures outlined by the Institutional Ethics Committee (IEC) and regulatory authorities.

Laboratories:

• Although the study primarily focuses on clinical interventions and outcome assessments rather than laboratory analyses, certain biochemical parameters such as fasting plasma glucose levels may be measured to confirm eligibility criteria or as secondary outcome measures.
• Laboratory facilities within the International Institute of Yoga and Naturopathy Medical Sciences or affiliated institutions may be utilized for any necessary laboratory analyses.
• The laboratories ensure accurate and timely processing of biological samples, adhering to standardized protocols and quality assurance measures.

Data Management Center:

• The Data Management Center is responsible for overseeing data collection, storage, and analysis throughout the study.
• It may be located within the International Institute of Yoga and Naturopathy Medical Sciences or in a separate facility equipped with appropriate infrastructure and personnel.
• The Data Management Center ensures the confidentiality, integrity, and security of all study-related data, adhering to Good Clinical Practice (GCP) guidelines and regulatory requirements.
• Data management activities include data entry, cleaning, coding, validation, and statistical analysis.

Coordinating Centre:

• The Coordinating Center serves as the central administrative hub responsible for coordinating various aspects of the study, including protocol development, regulatory submissions, participant recruitment, training of study personnel, and monitoring study progress.
• It may be housed within the International Institute of Yoga and Naturopathy Medical Sciences or operate as a separate entity closely collaborating with the study team.
• The Coordinating Center facilitates communication among investigators, study personnel, regulatory authorities, and other stakeholders involved in the research.
• It plays a pivotal role in ensuring the smooth implementation of the study protocol, addressing any issues or concerns, and maintaining overall study integrity and compliance.

Study Design:

• The experimental design of the study is a Pilot Randomized Controlled Trial (RCT).
• Participants will be randomly assigned to either a study group or a control group.
• The study is single-blind, where participants are blinded to the intervention group they are assigned to. However, due to the nature of the intervention, blinding of the practitioners administering the acupuncture may not be feasible.
• Allocation concealment will be ensured using the Sequentially Numbered Opaque Sealed Envelope (SNOSE) technique to minimize selection bias.

Study Population General Description:

• The study population comprises individuals aged 30-60 years.
• Participants have a confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) with an HbA1c level of ? 6.5%.
• They have been on diabetes medication for the past 3 months.
• Participants have not undergone acupuncture treatment in the past month.   Individuals willing to provide informed consent are eligible for inclusion in the study. 

• The sample size for the study is determined to be n=20, with 10 participants allocated to each group (study group and control group).
• The sample size determination is based on the pilot nature of the study, aiming to explore the feasibility and potential efficacy of auricular acupuncture in managing T2DM.
• Power analyses may not be conducted for a pilot study due to the exploratory nature of the research and the absence of predetermined effect sizes.

Study Outcomes/Endpoints:

Primary Outcome:

• Changes in mean glucose levels assessed via Freestyle Libre Pro continuous glucose monitoring.

 Secondary Outcomes:

• Changes in insulin sensitivity measured by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores.
• Continuous blood glucose levels will be measured using the Freestyle Libre Pro system
• The study aims to investigate the efficacy of auricular acupuncture targeting specific points in improving glycemic control and insulin sensitivity in individuals with T2DM.

Study Procedures

1. Subject Selection Procedures:

1. Sampling Plan including Inclusion/Exclusion Criteria:

Inclusion Criteria:

1. Age group 30-60 years.
2. Confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) with an HbA1c level ? 6.5%.
3. On diabetes medication for the past 3 months.
4. No prior acupuncture treatment in the past month.
5. Willingness to provide informed consent.

Exclusion Criteria:

1. Presence of open wounds, burns, or scalds in specific areas targeted for acupuncture.
2. Consumption of alcohol or psychotropic medication during the study period.
3. Diabetic complications.
4. Psychiatric illnesses other than mild depression.
5. Pregnancy or breastfeeding.
6. Current participation in other clinical studies.
7. Needle phobia.

Recruitment Procedures:

• Recruitment will primarily occur at the International Institute of Yoga and Naturopathy Medical Sciences, Chengalpattu (Outpatient Department), which serves as the primary study site.
• Consent will be obtained at the Outpatient Department of the International Institute of Yoga and Naturopathy Medical Sciences during the initial screening visit.
• Consent will be obtained before any study-related procedures are performed.
• Trained study personnel, including physicians or research assistants, will obtain consent from potential participants.  
• Potential participants will be provided with brochures or information sheets detailing the purpose, procedures, potential risks, and benefits of the study.

Screening Procedures:

• Screening procedures will involve assessing potential participants for eligibility based on the inclusion and exclusion criteria outlined in the study protocol.
• This may include reviewing medical records, obtaining medical history, performing physical examinations, and conducting laboratory tests (e.g., HbA1c levels, fasting plasma glucose).
• Additionally, participants may undergo assessments to ensure they meet the age criteria and have not undergone acupuncture treatment in the past month.
• The screening process may require one or multiple visits depending on the availability of required tests and assessments.
• The length of each screening visit will vary based on the complexity of procedures and participant factors but is generally expected to be relatively short, typically ranging from 30 minutes to an hour. 

Withdrawal criteria: 

Participants are free to withdraw from the study at any point in time, for any reason, with or without prior intimation to investigators or with or without prior permission from investigators. 

Randomization and Blinding:

Participants will be randomly divided (1:1 ratio) into either a study group or a control group using simple random methods with computerized randomization. A simple randomization procedure will be performed for 20 subjects with a 1:1 ratio to get a sample size of (n=10) in each group. Allocation concealment will be done using the SNOSE (Sequentially Numbered Opaque Sealed Envelope) technique. The participants will be blinded to the study and control group intervention. 

Study Intervention:

The study intervention involves two arms: the study group receiving auricular acupuncture and the control group receiving sham acupuncture.

• 1. Study Group Intervention:
• Participants allocated to the study group will undergo auricular acupuncture targeting specific points, including the pancreas point, endocrine point, and point zero.
• The acupuncture sessions will be conducted in a supine lying or sitting position for 30 minutes daily for a total of 14 days.
• Needling will be performed by trained acupuncture practitioners using sterile, disposable needles of appropriate gauge and length
• The acupuncture points will be located and needled according to established guidelines and standards of practice in acupuncture therapy.
• Participants will receive a standardized acupuncture protocol, and the number of needles, depth of insertion, and duration of needling will be consistent across sessions.
  2. Control Group Intervention:

• Participants allocated to the control group will receive sham acupuncture.
• Sham acupuncture involves the application of tape or adhesive material to simulate the placement of acupuncture needles without actual needling.
• Similar to the study group, participants in the control group will be positioned in a supine lying or sitting position for 30 minutes daily for 14 days.
• While participants in the control group will experience the sensation of tape application, they will not receive acupuncture needling.
• The sham acupuncture intervention is designed to control for non-specific effects such as placebo response or attention from the practitioner.
• Both study groups will be observed without any additional interventions during the 14-day period. Participants in both groups will be instructed to maintain their usual diabetes medication regimen and lifestyle practices throughout the study period unless otherwise advised by their healthcare provider.
• The intervention sessions will be conducted at the International Institute of Yoga and Naturopathy Medical Sciences, Chengalpattu, under the supervision of trained healthcare professionals. Any adverse events or discomfort experienced during the intervention will be monitored and managed appropriately.

Figure: 2 – Intervention Point and Its Location