OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline from the Women’s Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. RESULTS In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (hazard ratio in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24–1.37]) and plant protein with decreased risk (0.82 [0.78–0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (0.79 [0.74–0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG. CONCLUSIONS Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.

中文翻译：

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膳食蛋白质来源、介导生物标志物和 2 型糖尿病的发病率：来自妇女健康倡议和英国生物银行的调查结果

目的 膳食蛋白质摄入是否以及如何与 2 型糖尿病 (T2D) 相关仍不清楚。本研究的目的是调查蛋白质摄入与 T2D 发展的关系以及 T2D 生物标志物的潜在中介作用。研究设 Cox 比例风险模型用于估计蛋白质-T2D 关联。进行中介分析以评估生物标志物在嵌套在 WHI 中的病例对照研究中的中介作用。结果 在 WHI 中，在 15.8 年的中位随访期间发现了 15,842 例 T2D 病例。动物蛋白的摄入与 T2D 风险增加相关（最高与最低五分之一的风险比 = 1.31 [95% CI 1.24–1.37]）和植物蛋白的风险降低（0.82 [0.78–0.86]）。红肉、加工肉类、家禽和鸡蛋的摄入量与 T2D 风险增加有关，而全谷物与风险降低有关。UKB 的调查结果相似。在对 BMI 进行额外调整后，这些发现显着减弱。用 5% 的植物蛋白能量替代动物蛋白与 21% 的 T2D 风险降低相关（0.79 [0.74-0.84]），这是由 hs-CRP、白细胞介素 6、瘦素和 SHBG 水平介导的。结论 这两个大型前瞻性队列的结果支持这样一种观点，即用植物蛋白代替动物蛋白可能主要通过减少与肥胖相关的炎症来降低 T2D 风险。