A low-calorie Mediterranean diet combined with physical activity reduces the risk of diabetes

A study coordinated by the Biomedical Research Networking Centre (CIBER) of the Carlos III Health Institute (ISCIII), with the involvement of the UAB, confirms that adopting a low-calorie Mediterranean diet, together with increased physical activity, helps reduce the onset of new cases of type 2 diabetes in overweight people with high metabolic risk. The research has been published in Annals of Internal Medicine, the journal of the American College of Physicians.

This is evidenced by the initial results of the PREDIMED-Plus study, a Spanish multicentre clinical trial funded with more than €15 million through various calls for proposals, but with the majority of the funding coming from the ISCIII and the CIBER Consortium, which has followed thousands of people throughout Spain for six years.

More than 200 specialists from 23 Spanish universities and research centres have demonstrated, for the first time, that this combined strategy is effective in reducing the risk of developing type 2 diabetes.

Type 2 diabetes, a chronic disease that seriously impairs health and quality of life, has seen a notable increase in recent years, parallel to the obesity epidemic. It is therefore essential to promote accessible and sustainable strategies focused on prevention.

The PREDIMED (PREvention with a MEDiterranean Diet) study, which has been active for more than two decades, had already shown that a Mediterranean diet supplemented with extra virgin olive oil or nuts reduces the incidence of diabetes by 30% compared to a low-fat diet. However, this reduction was observed with a barely noticeable decrease in body weight.

Based on this knowledge, the PREDIMED-Plus study proposed a more intensive lifestyle intervention to assess whether it could provide additional benefits compared to other less intensive strategies. This strategy is based on weight loss through a slightly low-calorie Mediterranean diet—rich in fiber and low on the glycemic index—combined with the promotion of physical activity and behavioural support.

The study now published included 4,746 participants aged between 55 and 75 who were overweight or obese and had metabolic syndrome, but did not suffer from cardiovascular disease or diabetes at the start. Participants were randomly assigned (50% probability) to one of the following two programmes: one focused on following the Mediterranean diet (without promoting physical activity or pursuing a reduction in dietary calories), and another behavioural programme focused on achieving weight loss through a reduced-calorie Mediterranean diet (with a planned reduction of 600 kilocalories per day) and increased physical activity.

After 6 years of follow-up, it was observed that participants without diabetes at the start who were assigned to the intensive intervention group (Mediterranean diet and physical activity) showed greater adherence to the Mediterranean diet, increased their physical activity, lost more weight, and needed less medication to control their glucose during follow-up once diagnosed with diabetes.

In addition, the absolute risk of developing diabetes was 12% (349 cases) in participants who followed only the Mediterranean diet, compared to 9.5% (280 cases) in those assigned to the intensive intervention. The latter strategy reduced new cases of diabetes by 31% compared to the Mediterranean diet without calorie restriction or exercise recommendations.

The research team concludes that the foods and nutrients that make up the Mediterranean diet "act synergistically through different mechanisms involved in type 2 diabetes, such as reducing insulin resistance, inflammation, and oxidative stress. These effects are enhanced by physical activity and weight loss. Furthermore, as it is a tasty, sustainable, and culturally accepted diet, it can become an ideal long-term strategy for the prevention of cardiometabolic diseases."

PREDIMED-Plus, one of the largest nutrition and health trials conducted in Europe, is a randomised cardiovascular prevention trial based on lifestyle changes. In 2023, the journal Nature Medicine highlighted it among the 11 studies that will change medicine in the coming years, due to its scope and scientific relevance.

Ample collaboration throughout Spain

The PREDIMED-Plus study involved researchers from the Biomedical Research Networking Centre (CIBER)—part of the Carlos III Health Institute (ISCIII)—from three areas: Physiopathology of Obesity and Nutrition (CIBEROBN), Epidemiology and Public Health (CIBERESP), and Diabetes and Associated Metabolic Diseases (CIBERDEM).

Numerous research groups from various institutions have also collaborated, including: Rovira i Virgili University and Pere i Virgili Health Research Institute in Reus; University of Navarra, IdiSNA and Primary Care, Navarre Health Service; University of Valencia, Jaume I University and Valencian Regional Ministry of Health; IMIM-Hospital del Mar and Universitat Autònoma de Barcelona; Miguel Hernández University and UMH-ISABIAL (Alacant); Son Espases Hospital and IdISBa (Palma de Mallorca); University of Malaga and IBIMA; IMIBIC and Reina Sofia Hospital (Cordoba); Hospital Clinic and IDIBAPS (Barcelona); University of Granada; Bioaraba, Osakidetza, and UPV/EHU (Vitoria-Gasteiz); University of the Balearic Islands – IUNICS; Virgen de la Victoria Hospital and University of Malaga; University of Las Palmas de Gran Canaria; Institute of Biomedicine (IBIOMED), University of León, and Primary Care of León (Sacyl); Seville Primary Care Health District and University of Seville; Jiménez Díaz Foundation Hospital – IISFJD (Madrid); Bellvitge University Hospital – IDIBELL; San Carlos Clinical Hospital – IdISSC (Madrid); University of Jaén; IMDEA Food Institute. This scientific article was produced in collaboration with the Harvard T.H. Chan School of Public Health in the United States.

Original article:

Ruiz-Canela M, Corella D, Martínez-González MÁ, et al. Comparison of an energy-reduced Mediterranean diet and physical activity versus an ad libitum Mediterranean diet in the prevention of type 2 diabetes. A secondary analysis of a randomized controlled trial. Annals of Internal Medicine. 26 August 2025: doi:10.7326/ANNALS-25-00388