Boughanem Hatim, Gutierrez-Mariscal Francisco M, Arenas-de Larriva Antonio Pablo, Torres-Peña José D, Romero-Cabrera Juan L, Rangel-Zuñiga Oriol Alberto, García-Fernández Helena, Podadera-Herreros Alicia, Rodríguez-Cantalejo Fernando, Soehnlein Oliver, Macias-Gonzalez Manuel, Tinahones Francisco J, Yubero Serrano Elena M, Perez-Martinez Pablo, Delgado-Lista Javier, López-Miranda José
Lipids and Atherosclerosis Unit, Department of Internal Medicine, Hospital Universitario Reina Sofía, Cordoba, Spain.
Department of Medical and Surgical Sciences, Universidad de Cordoba, Cordoba, Spain.
Nutr Diabetes. 2025 Mar 27;15(1):11. doi: 10.1038/s41387-025-00360-3.
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.
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.
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.
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.
ID: NCT00924937; URL Clinical trial: https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 .
最近有证据表明饮食和体育活动与2型糖尿病（T2DM）缓解有关，但新出现的研究结果表明免疫系统失调可能起关键作用。本研究旨在调查中性粒细胞与T2DM缓解之间的关联。
我们对来自CORDIOPREV研究的新诊断T2DM患者（N = 183）进行了全面分析，这些患者未接受降糖治疗，并被随机分配接受地中海饮食或低脂饮食。患者分为两组：缓解者，即实现T2DM缓解的患者（n = 73），以及未缓解者，即在5年饮食干预期间未实现缓解的患者（n = 110）。在基线和随访5年时测量中性粒细胞计数及其相关比率（NER、NBR、NLR和NHR，分别用红细胞、嗜碱性粒细胞、淋巴细胞和高密度脂蛋白进行标准化）。
与最高三分位数相比，在地中海饮食（而非低脂饮食）的患者中，中性粒细胞计数最低的基线三分位数与T2DM缓解可能性增加相关[调整后风险比为4.23（95%置信区间：1.53 - 11.69）]，NER和NHR也观察到类似结果。考虑临床和中性粒细胞变量时，该模型的预测能力得出的曲线下面积为0.783（95%置信区间：0.680 - 0.822）。此外，5年后，缓解者的中性粒细胞计数低于未缓解者（p = 0.006），且与基线相比中性粒细胞计数显著下降（p = 0.001）。食用地中海饮食的缓解者中性粒细胞计数的下降在随访期后胰岛素敏感性和处置指数显著增加（p = 0.011和p = 0.018）。
这些发现表明中性粒细胞计数有助于识别在地中海饮食后更有可能实现T2DM缓解的患者，提示其对胰岛素敏感性和β细胞功能有作用。进一步的研究有望为T2DM的病理生理学提供有价值的见解。
编号：NCT00924937；网址 临床试验：https://clinicaltrials.gov/study/NCT00924937?cond=NCT00924937&rank=1 。
