Proteomic Signature of Body Mass Index and Risk of Type 2 Diabetes

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2024-11-19 DOI:10.2337/db24-0329

Xuan Wang, Hao Ma, Minghao Kou, Yoriko Heianza, Vivian Fonseca, Lu Qi

{"title":"Proteomic Signature of Body Mass Index and Risk of Type 2 Diabetes","authors":"Xuan Wang, Hao Ma, Minghao Kou, Yoriko Heianza, Vivian Fonseca, Lu Qi","doi":"10.2337/db24-0329","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"46 1","pages":""},"PeriodicalIF":6.2000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/db24-0329","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

体重指数与 2 型糖尿病风险的蛋白质组特征

以体重指数（BMI）诊断肥胖在代谢表型和罹患 2 型糖尿病（T2D）的风险方面表现出相当大的个体间异质性。我们研究了体重指数的蛋白质组特征与 T2D 的关联，并探讨了体重指数的蛋白质组特征是否能改善对 T2D 风险的预测。这项研究纳入了英国生物库中的 41427 名成年人，他们在基线时没有 T2D，并拥有通过基于抗体的 Olink 分析评估的蛋白质组指标的完整数据。主要暴露指标是蛋白质组 BMI 评分（pro-BMI 评分），该评分由 67 个预先确定的与 BMI 相关的血浆蛋白质计算得出。在中位 13.7 年的随访期间，共记录了 2,030 例 T2D 事件。我们发现，较高的蛋白质组 BMI（pro-BMI）得分与较高的 T2D 风险显著相关，而与实际 BMI、腰臀比和 BMI 的多基因风险得分无关（最高四分位数与最低四分位数的危险比（HR）为 3.81，95% CI，3.08 - 4.71）。当将 Pro- BMI 评分加入到年龄、性别和 BMI 的参考模型中时，C 指数会明显增加（C 指数变化为 0.023 [95%CI, 0.018 至 0.027]）。BMI 蛋白质组特征与 T2D 风险显著相关，与 BMI、WHR 和肥胖遗传易感性无关。如果将其添加到实际体重指数中，体重指数的蛋白质组特征可显著提高辨别能力，但提高幅度不大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.