Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Nutritional Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Nat Metab. 2024 Sep;6(9):1807-1818. doi: 10.1038/s42255-024-01109-5. Epub 2024 Aug 13.
Dietary haem iron intake is linked to an increased risk of type 2 diabetes (T2D), but the underlying plasma biomarkers are not well understood. We analysed data from 204,615 participants (79% females) in three large US cohorts over up to 36 years, examining the associations between iron intake and T2D risk. We also assessed plasma metabolic biomarkers and metabolomic profiles in subsets of 37,544 (82% females) and 9,024 (84% females) participants, respectively. Here we show that haem iron intake but not non-haem iron is associated with a higher T2D risk, with a multivariable-adjusted hazard ratio of 1.26 (95% confidence interval 1.20-1.33; P for trend <0.001) comparing the highest to the lowest quintiles. Haem iron accounts for significant proportions of the T2D risk linked to unprocessed red meat and specific dietary patterns. Increased haem iron intake correlates with unfavourable plasma profiles of insulinaemia, lipids, inflammation and T2D-linked metabolites. We also identify metabolites, including L-valine and uric acid, potentially mediating the haem iron-T2D relationship, highlighting their pivotal role in T2D pathogenesis.
膳食血红素铁的摄入量与 2 型糖尿病（T2D）风险增加有关，但潜在的血浆生物标志物尚不清楚。我们分析了来自三个美国大型队列的 204615 名参与者（79%为女性）的数据，这些参与者的随访时间长达 36 年，研究了铁摄入量与 T2D 风险之间的关联。我们还分别在 37544 名（82%为女性）和 9024 名（84%为女性）参与者的亚组中评估了血浆代谢生物标志物和代谢组学特征。在这里，我们表明血红素铁的摄入而不是非血红素铁的摄入与更高的 T2D 风险相关，多变量调整后的风险比为 1.26（95%置信区间为 1.20-1.33；趋势 P<0.001），将最高五分位数与最低五分位数进行比较。血红素铁占与未加工的红肉和特定饮食模式相关的 T2D 风险的很大比例。血红素铁摄入量的增加与胰岛素血症、脂质、炎症和 T2D 相关代谢物的不良血浆特征相关。我们还确定了一些代谢物，包括 L-缬氨酸和尿酸，它们可能介导血红素铁与 T2D 的关系，突出了它们在 T2D 发病机制中的关键作用。
