DiAOVE: a monocentric randomized double-blind controlled nutritional intervention trial assessing the effects of oleocanthal- and oleacein-rich extra virgin olive oil on glycaemic control, continuous glucose monitoring metrics and metabolic outcomes in adults with type 2 diabetes mellitus
Type 2 diabetes
Participants with type 2 diabetes mellitus will be randomly assigned in a 1:1 ratio to one of two parallel intervention groups for 12 weeks. Randomisation will be stratified by sex and baseline HbA1c level (<8% vs ≥8%) using computer-generated random allocation with permuted blocks of variable size. The study is double-blind, and both participants and investigators will remain masked to treatment allocation throughout the study. The intervention products will be packaged and labelled identically using alphanumeric codes to ensure blinding. The intervention consists of the complete replacement of the participant’s usual culinary oil with a specifically characterised extra virgin olive oil (EVOO). Participants allocated to the intervention group will receive EVOO with a high content of phenolic compounds, particularly oleocanthal and oleacein (AOVE-T), while the control group will receive a low-phenolic control EVOO obtained by phenolic extraction (“washed” EVOO) while preserving the lipid matrix (AOVE-C). Participants will be instructed to use exclusively the assigned oil both raw and for home cooking and to avoid other culinary oils or fats during the intervention period. Approximately 1 litre of EVOO per week will be supplied to each participant. No additional structured dietary modifications or caloric restriction will be prescribed. Glycaemic control will be assessed using glycated haemoglobin (HbA1c) and two 10-day periods of continuous glucose monitoring performed before and at the end of the intervention.
1. Men or women aged between 40 and 70 years 2. Diagnosis of type 2 diabetes mellitus established according to the criteria of the American Diabetes Association (ADA) 3. Excess body fat (preclinical or clinical obesity, according to the definition and diagnostic criteria for clinical obesity established by the 2025 Lancet Diabetes & Endocrinology Commission) determined by direct body fat measurement (DEXA scan) or fulfillment of at least two of the following criteria: 3.1. BMI ≥ 25 kg/m² 3.2. Waist circumference ≥ 102 cm for men or ≥ 88 cm for women 3.3. Waist-to-hip ratio > 0.90 for men or > 0.85 for women 3.4. Waist-to-height ratio > 0.5 for all participants 3.5. Excess body fat will be pragmatically assumed if BMI is > 40 kg/m². 4. Stable pharmacological treatment for T2DM for at least 3 or 6 months prior to inclusion, which may include: 4.1. Metformin (3 months) 4.2. DPP-4 inhibitors (3 months) 4.3. SGLT2 inhibitors (6 months) 4.4. GLP-1 receptor agonists (6 months) 5. Stable statin treatment, when indicated 6. Ability to understand the study information and provide written informed consent
1. Active chronic inflammatory diseases, such as Crohn's Disease, Ulcerative Colitis, inflammatory arthritis, or other systemic inflammatory disorders 2. Chronic treatment with nonsteroidal anti-inflammatory drugs or systemic corticosteroids within the previous 6 months. 3. Habitual consumption of meals outside the home three or more times per week, which would hinder adequate control of the dietary intervention 4. Use of hormonal contraceptives, pregnancy, breastfeeding, or steroid hormone replacement therapy 5. Current diagnosis of malignant neoplasia or history of neoplasia within the year prior to inclusion 6. Active smoking or former smokers with less than 5 years of abstinence 7. Having been born and having lived for most of the first 18 years of life (more than 10 years during the first 18 years) in countries not aligned with the traditional Mediterranean diet (countries other than Spain, Italy, Greece, Southern France [Provence-Alpes-Côte d’Azur region and the departments of Hérault, Gard, Aude, and Pyrénées-Orientales in the Occitanie region], Portugal, Croatia [Dalmatian Coast], Albania, Turkey [Aegean Coast], Lebanon, Israel, Morocco, and Tunisia) 8. Objective inability to comply with study procedures, defined as the presence of significant cognitive impairment, substantial language barriers, logistical inability to attend scheduled visits, anticipated major therapeutic changes during the intervention period, or any other documented circumstance preventing adequate compliance with the intervention and data collection, as appropriately recorded in the study records