Gallardo-Nuell Laura, Blanch Jordi, Leal Yenny, Coral Daniel E, Duarte-Salles Talita, Giordano Giuseppe N, Franks Paul W, Pearson Ewan R, Mingrone Geltrude, le Roux Carel W, Ramos Rafael, Fernández-Real José Manuel
Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta Hospital, Girona, Spain.
Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain.
Cardiovasc Diabetol. 2025 Mar 26;24(1):139. doi: 10.1186/s12933-025-02685-w.
Understanding the relationship between serum ferritin levels and cardiovascular outcomes in type 2 diabetes is crucial for improving risk stratification and guiding therapeutic interventions aimed at preventing major adverse cardiovascular events (MACE). This study aimed to identify distinct clusters of individuals with type 2 diabetes who have varying risks of MACE using a data-driven clustering approach.
This retrospective cohort study analyzed data from 49,506 individuals within a multicenter, population-based primary care registry in Catalonia, Spain. Individuals diagnosed with type 2 diabetes at age 35 or older were recruited between January 2010 and December 2021 and followed for at least 10 years. Biomarkers associated with cardiovascular risk-including serum glucose, HbA1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, serum ferritin, leukocyte, and monocyte counts-were examined. Clustering analysis was applied to identify patient subgroups, and Cox proportional hazards models were used to assess associations with cerebrovascular events, coronary events, and composite MACE.
Five distinct clusters were identified, characterized by differences in serum glucose, HbA1c, lipid profiles, blood pressure, and serum ferritin levels. Individuals with discordantly high serum ferritin levels relative to their body mass index (BMI) exhibited a lower risk of adverse cardiovascular outcomes. In men, hazard ratios (HR) were 0.68 (95% confidence interval [CI]: 0.53-0.87) for cerebrovascular events, 0.65 (95% CI 0.49-0.88) for coronary events, and 0.68 (95% CI 0.56-0.83) for MACE. In women, HRs were 0.81 (95% CI 0.67-0.92) for cerebrovascular events, 0.73 (95% CI 0.57-0.95) for coronary events, and 0.79 (95% CI 0.67-0.92) for MACE.
Individuals with type 2 diabetes who exhibit higher-than-expected serum ferritin levels relative to their BMI may have a lower risk of cardiovascular events. These findings suggest that ferritin may play a more complex role in cardiovascular risk than previously assumed and highlight the potential for refined risk stratification strategies in type 2 diabetes management.
了解2型糖尿病患者血清铁蛋白水平与心血管结局之间的关系，对于改善风险分层以及指导旨在预防主要不良心血管事件（MACE）的治疗干预措施至关重要。本研究旨在使用数据驱动的聚类方法，识别具有不同MACE风险的2型糖尿病患者的不同亚组。
这项回顾性队列研究分析了西班牙加泰罗尼亚一个基于人群的多中心初级保健登记处中49,506名个体的数据。2010年1月至2021年12月期间招募了35岁及以上被诊断为2型糖尿病的个体，并随访至少10年。检测了与心血管风险相关的生物标志物，包括血糖、糖化血红蛋白、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、甘油三酯、血压、血清铁蛋白、白细胞和单核细胞计数。应用聚类分析来识别患者亚组，并使用Cox比例风险模型评估与脑血管事件、冠状动脉事件和复合MACE的关联。
识别出五个不同的亚组，其特征在于血糖、糖化血红蛋白、血脂谱、血压和血清铁蛋白水平的差异。相对于体重指数（BMI）血清铁蛋白水平异常高的个体发生不良心血管结局的风险较低。在男性中，脑血管事件的风险比（HR）为0.68（95%置信区间[CI]：0.53 - 0.87），冠状动脉事件为0.65（95%CI 0.49 - 0.88），MACE为0.68（95%CI 0.56 - 0.83）。在女性中，脑血管事件的HR为0.81（95%CI 0.67 - 0.92），冠状动脉事件为0.73（95%CI 0.57 - 0.95），MACE为0.79（95%CI 0.67 - 0.92）。
相对于BMI而言，血清铁蛋白水平高于预期的2型糖尿病患者发生心血管事件的风险可能较低。这些发现表明，铁蛋白在心血管风险中的作用可能比以前认为的更为复杂，并突出了在2型糖尿病管理中优化风险分层策略的潜力。
