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

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.