Boughanem, H.; de Larriva, A. P. A.; Camargo, A.; Torres-Peña, J. D.; Ojeda-Rodriguez, A.; Alcala-Diaz, J. F.; Romero-Cabrera, J. L.; Rangel-Zuñiga, O. A.; Rodríguez-Cantalejo, F.; Soehnlein, O.; Macias-Gonzalez, M.; Tinahones, F. J.; Perez-Martinez, P.; Delgado-Lista, J.; López-Miranda, J.

2024 The Journal of Clinical Endocrinology & Metabolism 

Abstract

Context

Numerous studies have reported an association between neutrophils and type 2 diabetes mellitus (T2DM), although this relationship remains unclear.

Objective

To investigate the interaction of neutrophils and a dietary intervention on T2DM incidence after 60 months of follow-up.

Methods

A comprehensive analysis was conducted on the framework of the CORDIOPREV study, which included 462 patients without T2DM at the beginning of the study, randomly assigned to either a Mediterranean or a low-fat diet; 107 developed T2DM. Absolute neutrophil counts and neutrophil-related ratios were measured.

Results

Kaplan-Meier curves showed that the lowest tertile of basal neutrophils was associated with a reduced likelihood of T2DM incidence when compared to the middle (hazard ratio [HR] = 0.499 [95% CI, 0.287-0.866]) and the highest tertiles (HR = 0.442 [95% CI, 0.255-0.768]) in the overall population, after adjusting for clinical variables. This association only remained significant in patients who followed a Mediterranean diet when comparing the lowest to the middle (HR = 0.423 [95% CI, 0.213-0.842]) and the highest tertiles (HR = 0.371 [95% CI, 0.182-0.762]). The predictive capacity yielded an AUC of 0.711 (95% CI, 0.652-0.769), with neutrophils being the most important variable in the in the model. Decrease in neutrophils over the 60 months was associated with increased insulin sensitivity index (R = −0.31; P = .019), particularly in patients who followed the Mediterranean diet.

Conclusion

These findings suggest that monitoring neutrophils can help prevent the development of T2DM, as a reduction in neutrophil counts could be associated with improved insulin sensitivity. Following a Mediterranean diet might be a potential strategy to reduce the incidence of T2DM by lowering neutrophil levels. Further research is necessary to gain a deeper understanding regarding this mechanism.