Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers. This study aimed to investigate metabolite biomarkers of meat intake and their associations with T2D risk. Fasting plasma samples were collected from a case–control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow-up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed, and unprocessed red meat and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) ( = 4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts. In total, 15 metabolites were associated with ≥1 meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake [ > 0.22, false discovery rate (FDR) < 0.001 for VIP and > 0.05; FDR < 0.001 for SMCC) were consistently associated with higher T2D risk in both data sets. Conversely, lysophosphatidylcholine 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake ( < −0.12; FDR < 0.023, for VIP and < −0.05; FDR < 0.001, for SMCC) and with lower T2D risk in both data sets, except for PC 15:0/18:2, which was significant only in the VIP cohort. All associations were attenuated after adjustment for BMI (kg/m). Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.

中文翻译：

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两个瑞典队列中反映肉类消费的空腹血浆代谢物及其与 2 型糖尿病事件的关联

食用加工红肉与患 2 型糖尿病 (T2D) 的风险增加有关，但饮食评估面临的挑战需要客观的摄入生物标志物。本研究旨在调查肉类摄入的代谢生物标志物及其与 T2D 风险的关联。空腹血浆样本取自西博滕干预计划 (VIP) 内的一项病例对照研究（214 名女性和 189 名男性），这些患者在中位随访 7 年后患上 T2D。反映总的、加工的和未加工的红肉和家禽消费量的候选生物标志物组是从对照收集的非目标代谢组学数据中选择的。然后在乌普萨拉 (SMCC) 的瑞典乳房 X 线摄影临床子队列（= 4457 名女性）中复制了观察到的关联。使用发现中的多变量条件逻辑回归和复制队列中的 Cox 回归来评估复制代谢物与 T2D 风险的潜在关联。总共有 15 种代谢物与两个队列中≥1 个肉类组相关。酰基肉碱 8:1、8:2、10:3，反映出较高的加工肉类摄入量 [ > 0.22，VIP 的错误发现率 (FDR) < 0.001 且 > 0.05；在两个数据集中，SMCC 的 FDR < 0.001 均与较高的 T2D 风险相关。相反，溶血磷脂酰胆碱 17:1 和磷脂酰胆碱 (PC) 15:0/18:2 与较低的加工肉类摄入量相关（对于 VIP，< -0.12；FDR < 0.023；对于 SMCC，< -0.05；FDR < 0.001）。两个数据集中的 T2D 风险均较低，但 PC 15:0/18:2 除外，该数据仅在 VIP 队列中显着。调整 BMI (kg/m) 后，所有关联均减弱。参与脂质代谢的候选生物标志物在较高的加工红肉摄入量与较高的 T2D 风险之间以及反映较低摄入量与较低风险之间存在一致的关联，这可能表明加工肉类摄入量与较高的 T2D 风险之间存在关系。然而，调整 BMI 后相关性减弱表明这种关系可能至少部分受到 BMI 的调节或混淆。