Effect of long-term Mediterranean versus low-fat diet on neutrophil count, and type 2 diabetes mellitus remission in patients with coronary heart disease: results from the CORDIOPREV study

Abstract Background Recent evidence links diet and physical activity with type 2 diabetes mellitus (T2DM) remission, but emerging findings suggest that immune system dysregulation may play a crucial role. This study aimed to investigate the associations between neutrophils and T2DM remission. Method...

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Main Authors: Hatim Boughanem, Francisco M. Gutierrez-Mariscal, Antonio Pablo Arenas-de Larriva, José D. Torres-Peña, Juan L. Romero-Cabrera, Oriol Alberto Rangel-Zuñiga, Helena García-Fernández, Alicia Podadera-Herreros, Fernando Rodríguez-Cantalejo, Oliver Soehnlein, Manuel Macias-Gonzalez, Francisco J. Tinahones, Elena M. Yubero Serrano, Pablo Perez-Martinez, Javier Delgado-Lista, José López-Miranda
Format: Article
Language:English
Published: Nature Publishing Group 2025-03-01
Series:Nutrition & Diabetes
Online Access:https://doi.org/10.1038/s41387-025-00360-3
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Summary:Abstract Background Recent evidence links diet and physical activity with type 2 diabetes mellitus (T2DM) remission, but emerging findings suggest that immune system dysregulation may play a crucial role. This study aimed to investigate the associations between neutrophils and T2DM remission. Methods We conducted a comprehensive analysis of newly-diagnosed T2DM patients (N = 183) from the CORDIOPREV study, without glucose-lowering treatment, and were randomized to follow either a Mediterranean or low-fat diet. Patients were classified into two groups: Responders, who achieved T2DM remission (n = 73), and Non-Responders, who did not achieve remission during the 5-year dietary intervention (n = 110). Neutrophil count and their related-ratio (NER, NBR, NLR and NHR, normalized with erythrocytes, basophils, lymphocytes, and HDL respectively) were measured at the baseline and 5 years of follow-up. Results The lowest baseline tertile of neutrophil count was associated with an increased likelihood of T2DM remission among patients following a Mediterranean diet (but not for low-fat diet) when compared with the highest tertile [adjusted HR of 4.23 (95% CI: 1.53–11.69)], in which similar results were observed for NER and NHR. When considering clinical and neutrophil variables, the predictive capacity of this model yielded an AUC of 0.783 (95% CI: 0.680–0.822). Furthermore, after 5-years, Responders exhibited lower neutrophil count compared to Non-responders (p = 0.006) and a significant decrease in neutrophil count (p = 0.001) compared to baseline. This decrease in neutrophil count in Responders who consumed a Mediterranean diet exhibited a significant increase in Insulin Sensitivity and Disposition Index (p = 0.011 and p = 0.018) after the follow-up period. Conclusion These findings suggest that neutrophil count can help in identifying patients that are more likely to achieve T2DM remission following a Mediterranean diet, suggesting a role on insulin sensitivity and β-cell function. Further research holds promise for providing valuable insights into the pathophysiology of T2DM. Clinical trial Registration ID: NCT00924937; URL Clinical trial: https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 .
ISSN:2044-4052