Effect of an Intervention With Apple Cider Vinegar on Glycemic Variability and Lipid Profile in Patients With Type 2 Diabetes Mellitus

Effect of an Intervention With Apple Cider Vinegar on Glycemic Variability and Lipid Profile in Patients With Type 2 Diabetes Mellitus

The objective of this open-label, randomized, crossover clinical trial is to determine the effect of consuming 15 ml of organic apple cider vinegar on glycemic variability, measured by the coefficient of variation of glucose, in adults with type 2 diabetes mellitus. The main question this study seeks to answer is: What is the effect of consuming 15 ml of organic apple cider vinegar every 12 hours for a period of 2 weeks on the coefficient of variation of glucose in adults aged 18 to 60 years with type 2 diabetes mellitus, compared to consuming 250 ml of natural water? The researchers will compare the consumption of organic apple cider vinegar with natural water to evaluate whether organic apple cider vinegar has an impact on glycemic variability. Participants, in a crossover design, will use a continuous glucose monitor throughout the study. In one phase, they will consume 15 ml of apple cider vinegar before breakfast and before dinner for a period of 14 days, and in the other phase, they will consume 250 ml of natural water for the same period, with a washout period between both phases. Glucose data obtained through the continuous glucose monitor will be used to calculate the coefficient of variation as the primary measure of glycemic variability.

1. Background and Rationale Type 2 diabetes mellitus (T2DM) represents a significant public health challenge worldwide, characterized by hyperglycemia resulting from insulin resistance and relative insulin secretion deficiency. The management of T2DM focuses on glycemic control to prevent micro- and macrovascular complications. While glycosylated hemoglobin (HbA1c) is a standard measure of long-term glycemic control, it has limitations in detecting short-term glucose fluctuations, known as glycemic variability. Growing evidence suggests that high glycemic variability is associated with an increased risk of complications, independent of average HbA1c.

   Apple cider vinegar (ACV) has gained attention as a potential adjunct for glucose management. Among the main proposed mechanisms by which vinegar might have some effect on glucose metabolism are the modulation of gastric emptying and the improvement of insulin sensitivity, according to preliminary studies. However, evidence on its specific impact on glycemic variability in adults with T2DM is limited and requires rigorous investigation. This clinical trial seeks to address this knowledge gap by evaluating the effect of organic apple cider vinegar consumption on glycemic variability, using the coefficient of variation (CV) of glucose as the primary outcome measure, compared to a natural water control.

2. Study Design:

   An open-label, randomized, crossover clinical trial will be implemented. The crossover design will allow each participant to act as their own control, reducing inter-individual variability and increasing statistical power. Eligible participants will be randomized to one of two treatment sequences: (A) 14 days of consuming 15 ml of organic apple cider vinegar twice daily, followed by a one-week washout period, and then 14 days of consuming 250 ml of natural water twice daily; or (B) 14 days of consuming 250 ml of natural water twice daily, followed by a one-week washout period, and then 14 days of consuming 15 ml of organic apple cider vinegar twice daily. The one-week washout period aims to minimize any residual effects of the previous intervention before the next phase.

3. Study Population:

   Approximately 38 adult participants (men and women) aged 18 to 60 years with a confirmed diagnosis of type 2 diabetes mellitus who meet the inclusion criteria will be recruited. Recruitment will be carried out for the general public. Written informed consent will be obtained from all participants before their inclusion in the study.

   During the apple cider vinegar intervention phase, participants will consume 15 ml of organic apple cider vinegar diluted in 250 ml of water before breakfast and dinner. During the control phase, participants will consume 250 ml of natural water at the same times. Participants will be instructed to maintain their usual dietary and physical activity habits throughout the study and to avoid the consumption of other products containing vinegar.

4. Outcome Measures The primary outcome measure will be the change in glycemic variability, quantified by the coefficient of variation (CV) of glucose. Glucose data will be obtained from a continuous glucose monitor (CGM) that participants will use for the 14 days of each intervention phase. The CV will be calculated for each participant in each phase using all available glucose data during the intervention period.

   Secondary outcome measures include:

   Changes in body composition (percentage of fat mass, weight, and visceral fat) measured at the beginning and end of each phase using bioelectrical impedance.

   Changes in serum triglyceride concentrations, measured by venous blood analysis drawn at the beginning and end of each phase.

   Changes in the subjective perception of hunger and satiety, assessed using the Visual Analog Scale administered during a mixed meal tolerance test.

5. Statistical Analysis Descriptive Variables Normality: Normality analysis will be performed using the Shapiro-Wilk test. Continuous quantitative variables with normal distribution: Data will be presented as means and standard deviations.

   Continuous quantitative variables without normal distribution: Data will be presented as medians and quartiles (Q1-Q3).

   Qualitative variables: Qualitative variables will be presented as frequency and percentage.

   Comparison between participants with and without apple cider vinegar Data will be captured and analyzed using the STATA statistical software version 16. A p-value less than 0.05 will be considered statistically significant.

   A multivariate analysis using multiple linear regression will be performed to evaluate the effect of apple cider vinegar, adjusting for other variables such as diet, physical activity level, and treatment for type 2 diabetes mellitus.

6. Ethical Considerations This study will be conducted in compliance with the ethical principles of the Declaration of Helsinki and has been approved by the research and ethics committee of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Written informed consent will be obtained from all participants before their inclusion. The confidentiality of participants' personal and medical information will be guaranteed throughout the study and in the dissemination of the results.

Inclusion Criteria:

• Men and women
• Diagnosis of type 2 diabetes mellitus
• Age between 18 and 60 years
• Glycated hemoglobin (HbA1c) ≤ 8%
• Participant's ability to attend medical appointments, answer questionnaires, and undergo laboratory tests.
• Participant's ability to wear a Freestyle® device.
• Participant's acceptance and signature of informed consent.
• Acceptance of the intervention (consumption of 30 ml of apple cider vinegar) and avoidance of vinegar-based dressings for the entire duration of the intervention.
• Consent to participate in the study.

Exclusion Criteria:

• Other types of diabetes
• Chronic kidney disease (eGFR < 60 ml/min)
• Allergy to apple cider vinegar
• Use of systemic steroids at supraphysiological doses
• Gastroesophageal reflux disease
• Peptic ulcer disease
• Documented gastroparesis
• Pregnancy or lactation
• Use of rapid-acting prandial insulin or analogs