Genetic subtypes of prediabetes, healthy lifestyle, and risk of type 2 diabetes

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-04-11 DOI:10.2337/db23-0699
Yang Li, Guo-Chong Chen, Jee-Young Moon, Rhonda Arthur, Daniela Sotres-Alvarez, Martha L. Daviglus, Amber Pirzada, Josiemer Mattei, Krista M. Perreira, Jerome I. Rotter, Kent D. Taylor, Yii-Der Ida Chen, Sylvia Wassertheil-Smoller, Tao Wang, Thomas E. Rohan, Joel D. Kaufman, Robert Kaplan, Qibin Qi
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Abstract

Prediabetes is a heterogenous metabolic state with various risk for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic whites without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n=3,677) and UKBB (n=16,284) separately, based on these pPRSs. Six clusters of individuals with prediabetes with distinctive patterns of pPRSs and corresponding metabolic traits were identified in the HCHS/SOL, five of which were confirmed in the UKBB. Although baseline glycemic traits were similar across clusters, individuals in Cluster 5 and Cluster 6 showed elevated risk of T2D during follow-up compared to Cluster 1 (RR=1.29 [95% CI 1.08-1.53] and1.34 [1.13-1.60], respectively). Inverse associations between a healthy lifestyle score and risk of T2D were observed across different clusters, with a suggestively stronger association observed in Cluster 5 compared to Cluster 1. Among individuals with healthy lifestyle, those in Cluster 5 had a similar risk of T2D compared to those in Cluster 1 (RR=1.03 [0.91-1.18]). This study identified genetic subtypes of prediabetes which differed in risk of progression to T2D and in benefits from healthy lifestyle.
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糖尿病前期的基因亚型、健康生活方式和 2 型糖尿病风险
糖尿病前期是一种异质性代谢状态,具有不同的发展为 2 型糖尿病(T2D)的风险。在这项研究中,我们利用西班牙裔社区健康研究/拉美裔研究(HCHS/SOL)中 7,227 名未患糖尿病的美国西班牙裔/拉美裔人和英国生物库(UKBB)中 400,149 名未患糖尿病的非西班牙裔白人的基因数据,计算出了代表与 T2D 相关的各种途径的五个分区多基因风险评分 (pPRS)。根据这些pPRS,分别对HCHS/SOL(n=3,677)和UKBB(n=16,284)中的糖尿病前期参与者进行了共识聚类。在HCHS/SOL中发现了六个具有独特pPRSs模式和相应代谢特征的糖尿病前期患者群组,其中五个群组在UKBB中得到了证实。虽然各组群的基线血糖特征相似,但与组群 1 相比,组群 5 和组群 6 中的个体在随访期间患 T2D 的风险较高(RR 分别为 1.29 [95% CI 1.08-1.53] 和 1.34 [1.13-1.60])。健康生活方式评分与 T2D 风险之间的反向关系在不同群组中均有观察到,与群组 1 相比,群组 5 中的反向关系更强。在拥有健康生活方式的个体中,群组 5 的个体与群组 1 的个体相比,患 T2D 的风险相似(RR=1.03 [0.91-1.18])。这项研究确定了糖尿病前期的遗传亚型,这些亚型在发展为 T2D 的风险和从健康生活方式中获益方面存在差异。
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来源期刊
Diabetes
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.
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