Spanish study describes that hypocaloric Mediterranean diet combined with physical activity reduces the risk of diabetes

A Spanish study, coordinated by the CIBER Research Center of the Instituto de Salud Carlos III (ISCIII) confirms that adopting a hypocaloric Mediterranean diet, together with increased physical activity, helps reduce the development of new cases of type 2 diabetes in people with overweight or obesity at high metabolic risk. The research has been published in Annals of Internal Medicine, the American College of Physicians journal.

These are the first results of the PREDIMED-Plus study, a Spanish multicenter clinical trial funded with more than €15 million, which has followed thousands of people across Spain during six years. More than 200 researchers from 23 centers in Spain (universities and hospitals) show, for the first time and with solid evidence, that this combined strategy is effective for reducing the risk of developing type 2 diabetes.

Type 2 diabetes is a chronic disease that seriously harms health and quality of life. The prevalence of this chronic condition has increased in recent years, following the trend of obesity epidemic. For this reason, it is essential to promote accessible and sustainable strategies focused on prevention.

For more than two decades, the PREDIMED study had already demonstrated that a Mediterranean diet, supplemented with extra-virgin olive oil or nuts, reduced the diabetes incidence by 30% compared with a low-fat diet. However, this reduction was observed with only a barely perceptible body weight decrease.

Based on that knowledge, the PREDIMED-Plus study introduced a more intensive lifestyle intervention, aimed at assessing whether it could provide additional benefits compared with other less intensive strategies. This approach is based on weight loss through a slightly hypocaloric Mediterranean diet (fiber-rich and having a low glycemic index) combined with the promotion of physical activity and behavioral support.

The current study involved 4,746 participants between 55 and 75 years old, all with overweight or obesity and metabolic syndrome, and none of whom had cardiovascular disease or diabetes at the beginning. Participants were randomly assigned (probability 50%) to one of these two programs: the first one focused on Mediterranean diet (without promoting physical activity or calories reduction in the diet), and the other one based on a behavioral program for obtaining weight loss through a reduced-calorie Mediterranean diet (reduction of 600 kcal/day) and higher physical activity.

After six years of follow-up, participants without diabetes at baseline 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 fewer glucose-control medications once they were diagnosed with diabetes.

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

The researchers conclude that the foods and nutrients in 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. Moreover, as Mediterranean diet is a tasty, sustainable and culturally accepted diet, it becomes a perfect long-term strategy for the prevention of cardiometabolic diseases”.

PREDIMED-Plus is one of the largest nutrition and health trials conducted in Europe. It is a randomized trial for cardiovascular prevention based on lifestyle changes. In 2023, Nature Medicine highlighted it among the 11 studies expected to change medicine in the following years, due to its impact and scientific relevance.

Extensive collaboration across Spain

The PREDIMED-Plus study involved researchers from the CIBER (Centro de Investigación Biomedica en Red) – part of the Instituto de Salud Carlos III – from three different research areas: Physiopathology of Obesity and Nutrition (CIBEROBN), Epidemiology and Public Health (CIBERESP), and Diabetes and Associated Metabolic Diseases (CIBERDEM). 

Moreover, several research groups from many institutions have collaborated, including: Universitat Rovira i Virgili and Institut d’Investigació Sanitària Pere i Virgili (Reus); University of Navarra, IdiSNA and Servicio Navarro de Salud; University of Valencia, Universitat Jaume I and Conselleria de Sanitat Valenciana; IMIM-Hospital del Mar and Universitat Autònoma de Barcelona; Universidad Miguel Hernández and UMH-ISABIAL (Alicante); Hospital Son Espases and IdISBa (Palma de Mallorca); University of Málaga and IBIMA; IMIBIC and Hospital Reina Sofía (Córdoba); Hospital Clínic and IDIBAPS (Barcelona); University of Granada; Bioaraba, Osakidetza and UPV/EHU (Vitoria-Gasteiz); University of the Balearic Islands – IUNICS; Hospital Virgen de la Victoria; University of Las Palmas de Gran Canaria; Institute of Biomedicine (IBIOMED), University of León and Primary Care in León (Sacyl); Primary Care Health District of Seville and University of Seville; Hospital Fundación Jiménez Díaz – IISFJD (Madrid); Hospital Universitario de Bellvitge – IDIBELL; Hospital Clínico San Carlos – IdISSC (Madrid); University of Jaén; IMDEA Food Institute. For this scientific article, the Harvard T.H. Chan School of Public Health (USA) also collaborated.

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. Ann Intern Med. 26 August 2025. [Epub ahead of print]. doi:10.7326/ANNALS-25-00388