Nutrition & Diabetes (Mar 2025)

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

  • 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

DOI
https://doi.org/10.1038/s41387-025-00360-3
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 8

Abstract

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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 .