The obesity diagnosis by body mass index (BMI) exhibits considerable interindividual heterogeneity in metabolic phenotypes and risk of developing type 2 diabetes (T2D). We investigated the association of proteomic signature of BMI and T2D and examined whether the proteomic signature of BMI improves prediction of T2D risk. This study included 41,427 adults in the UK Biobank who were free of T2D at baseline and had complete data on proteomics metrics assessed by antibody based Olink assay. The main exposure was a proteomic BMI score (pro-BMI score) calculated from 67 pre-identified plasma proteins associated with BMI. During a median follow-up of 13.7 years, 2,030 incident events of T2D were documented. We observed that a higher proteomic BMI (pro-BMI) score was significantly associated with a higher risk of T2D independent of actual BMI, waist-to-hip ratio, and polygenic risk score for BMI (hazard ratio (HR) comparing the highest with the lowest quartiles was 3.81, 95% CI, 3.08 – 4.71). Pro- BMI score significantly increased the C index when added to a reference model with age, sex, and BMI (C index change, 0.023 [95%CI, 0.018 to 0.027]). Proteomic signature of BMI is significantly associated with the risk of T2D independent of BMI, WHR and genetic susceptibility to obesity. When added to actual BMI, the proteomic signature of BMI provides significant but modest improvement in discrimination.

中文翻译：

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体重指数的蛋白质组学特征和 2 型糖尿病的风险


通过体重指数 （BMI） 诊断肥胖在代谢表型和患 2 型糖尿病 （T2D） 的风险方面表现出相当大的个体间异质性。我们调查了 BMI 和 T2D 的蛋白质组学特征的关联，并研究了 BMI 的蛋白质组学特征是否能提高 T2D 风险的预测。这项研究包括英国生物库中的 41,427 名成年人，他们在基线时没有 T2D，并且通过基于抗体的 Olink 测定评估了蛋白质组学指标的完整数据。主要暴露是由 67 种预先确定的与 BMI 相关的血浆蛋白计算的蛋白质组学 BMI 评分 （pro-BMI 评分）。在中位随访 13.7 年期间，记录了 2,030 例 T2D 事件。我们观察到较高的蛋白质组学 BMI （pro-BMI） 评分与较高的 T2D 风险显著相关，这与实际 BMI、腰臀比和 BMI 的多基因风险评分无关（风险比 （HR） 与最高四分位数相比为 3.81,95% CI，3.08 – 4.71）。当添加到具有年龄、性别和 BMI 的参考模型时，Pro- BMI 评分显着增加了 C 指数 （C 指数变化，0.023 [95%CI，0.018 至 0.027]）。BMI 的蛋白质组学特征与 T2D 风险显著相关，与 BMI 、 WHR 和肥胖的遗传易感性无关。当添加到实际 BMI 中时，BMI 的蛋白质组学特征在辨别方面提供了显着但适度的改善。