A groundbreaking new study emerging from Spain has delivered compelling evidence that modest, sustained lifestyle modifications centering on a calorie-reduced Mediterranean diet paired with increased physical activity can dramatically reduce the risk of developing type 2 diabetes. This large-scale, multicenter randomized controlled trial, known as PREDIMED-Plus, involved over 4,700 participants across multiple Spanish institutions and marks a pivotal advancement in our understanding of diabetes prevention. The implications extend worldwide, offering a viable, accessible strategy to stem the escalating global epidemic of type 2 diabetes.
The PREDIMED-Plus trial specifically targeted men and women aged 55 to 75 years who exhibited overweight or obesity coupled with metabolic syndrome—a constellation of conditions that substantially heighten diabetes risk but who had no prior cardiovascular disease or diabetes diagnosis. Participants were closely monitored over a six-year period, enabling researchers to rigorously compare two intervention groups. One group adopted an energy-restricted Mediterranean diet—with calorie reduction averaging around 600 kcal per day—combined with moderate-intensity exercise and professional support for weight management. The control group continued with a traditional Mediterranean diet without explicit calorie or exercise recommendations.
Technically, the study design optimized the Mediterranean dietary pattern known for its high content of monounsaturated fats, particularly from extra-virgin olive oil and nuts, with an integrated approach emphasizing caloric deficit and structured physical activity. The exercise regimen primarily consisted of brisk walking, resistance training, and balance exercises, designed to improve insulin sensitivity and enhance metabolic health, reflecting a well-rounded lifestyle intervention. The clinical rigor and randomized controlled methodology lend considerable weight to the findings and mitigate bias or confounding influences.
Analysis of the outcomes revealed that the intervention group achieved a striking 31% relative reduction in the incidence of type 2 diabetes compared to controls. Beyond the primary endpoint, participants in the intervention cohort demonstrated significant and sustained weight loss averaging 3.3 kilograms and a decrease in waist circumference of 3.6 centimeters. These anthropometric improvements underscore the synergy between dietary energy restriction, physical activity, and metabolic regulation in mitigating diabetes risk.
From a pathophysiological perspective, the Mediterranean diet modulates several key biochemical pathways linked to diabetes onset. Its combination of polyphenol-rich foods, balanced macronutrient profile, and anti-inflammatory constituents enhances insulin signaling and reduces systemic inflammation—two critical factors driving type 2 diabetes progression. Adding calorie restriction and exercise amplifies these pathways by improving cellular glucose uptake and promoting a favorable lipid profile, thereby reducing the metabolic strain on pancreatic beta-cells.
The broader context of this research is the alarming rise of type 2 diabetes globally, currently affecting over 530 million individuals. Urbanization, sedentary behaviors, and caloric excess have converged to fuel this epidemic, imposing a staggering public health and economic burden. The Spanish population studied epitomizes these risk factors, with nearly 4.7 million adults living with diabetes and a prevalence among the highest in Europe. Internationally, countries including the USA face similar challenges alongside elevated healthcare costs per diabetic patient.
Experts involved in the study emphasize that while pharmacological treatments garner significant attention, lifestyle interventions remain an indispensable cornerstone of diabetes prevention. The PREDIMED-Plus results confirm that real-world, manageable modifications—grounded in culturally acceptable and sustainable behaviors—yield substantive health dividends. This positions the intervention as a pragmatic model for public health initiatives and primary care integration, capable of reaching diverse populations at risk.
Furthermore, the study received commendation in an accompanying editorial published in the Annals of Internal Medicine. Public health specialists noted the clinical significance and scalability of the intervention while highlighting challenges in transplanting such models to non-Mediterranean populations where structural barriers like food deserts, socioeconomic inequality, and limited health literacy prevail. Consequently, efforts to implement this strategy must be tailored and supported by policies that improve access to nutritious foods and environments conducive to physical activity.
The origins of PREDIMED-Plus trace back to the original PREDIMED trial (2003-2010), which conclusively demonstrated a 30% reduction in cardiovascular events through a Mediterranean diet enriched with extra-virgin olive oil or nuts. The continuation and expansion of this research integrate weight loss and physical activity components to target diabetes directly, representing an evolution in preventive cardiometabolic research. The study was facilitated by a collaborative network of over 200 researchers from 22 Spanish centers, leveraging European funding exceeding 15 million euros.
International cooperation also played a vital role, with partnerships including the Harvard T.H. Chan School of Public Health enhancing the study’s epidemiological rigor and global applicability. The participating institutions encompassed a diverse array of universities and hospitals across Spain, highlighting the multidisciplinary and nationwide commitment to combating metabolic disease.
In summary, the PREDIMED-Plus trial provides robust, clinically actionable evidence asserting that an energy-reduced Mediterranean diet combined with moderate physical activity orchestrated through professional guidance constitutes an effective preventive strategy against type 2 diabetes. The trial’s success underscores the importance of adopting lifestyle interventions as a frontline defense, with potential to alleviate an urgent global health crisis by preventing thousands of new diabetes cases each year when applied at scale.
As the global burden of diabetes continues to mount, these findings herald a paradigm shift in chronic disease prevention—one that marries the rich tradition of Mediterranean nutrition with contemporary, evidence-based lifestyle medicine. Future research is anticipated to explore further metabolic endpoints and chronic conditions, but for now, these data strongly advocate for integrating such lifestyle prescriptions into clinical practice and public health policies worldwide.
Subject of Research: People
Article Title: 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
News Publication Date: 26-Aug-2025
Web References:
PREDIMED-Plus project: https://www.predimedplus.com/en/project/
University of Navarra: https://en.unav.edu/inicio
European Research Council (ERC): https://erc.europa.eu/homepage
Carlos III Health Institute (ISCIII): https://www.isciii.es/
CIBER research networks:
https://www.ciberobn.es/en
https://www.ciberesp.es/en
https://www.ciberdem.org/en
International Diabetes Federation: https://idf.org/about-diabetes/diabetes-facts-figures/
References:
Martínez-González, M. Á., Ruíz-Canela, M., et al. (2025). 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. DOI: 10.7326/ANNALS-25-00388
Image Credits: Manuel Castells/Miriam Salcedo
Keywords: Mediterranean diet, type 2 diabetes prevention, calorie restriction, physical activity, randomized controlled trial, metabolic syndrome, lifestyle intervention, public health, PREDIMED-Plus, weight loss, insulin sensitivity, chronic disease prevention
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