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Genetic subtypes of prediabetes, healthy lifestyle, and risk of type 2 diabetes
Diabetes ( IF 7.7 ) Pub Date : 2024-04-11 , DOI: 10.2337/db23-0699
Yang Li 1 , Guo-Chong Chen 2 , Jee-Young Moon 1 , Rhonda Arthur 1 , Daniela Sotres-Alvarez 3 , Martha L. Daviglus 4 , Amber Pirzada 4 , Josiemer Mattei 5 , Krista M. Perreira 6 , Jerome I. Rotter 7 , Kent D. Taylor 7 , Yii-Der Ida Chen 7 , Sylvia Wassertheil-Smoller 1 , Tao Wang 1 , Thomas E. Rohan 1 , Joel D. Kaufman 8 , Robert Kaplan 1 , Qibin Qi 1
Affiliation  

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.

中文翻译:

糖尿病前期的遗传亚型、健康生活方式和 2 型糖尿病风险

糖尿病前期是一种异质代谢状态,具有多种发展为 2 型糖尿病 (T2D) 的风险。在这项研究中,我们使用来自西班牙社区健康研究/拉丁裔研究 (HCHS/SOL) 的 7,227 名没有糖尿病的美国西班牙裔/拉丁裔的遗传数据和来自英国生物银行 (UKBB) 的 400,149 名没有糖尿病的非西班牙裔白人的遗传数据来计算五个分区多基因风险评分 (pPRS) 代表与 T2D 相关的各种途径。根据这些 pPRS,分别对 HCHS/SOL (n=3,677) 和 UKBB (n=16,284) 糖尿病前期参与者进行共识聚类。在 HCHS/SOL 中发现了六组具有独特 pPRS 模式和相应代谢特征的糖尿病前期个体,其中 5 组在 UKBB 中得到了证实。尽管各簇之间的基线血糖特征相似,但与簇 1 相比,簇 5 和簇 6 中的个体在随访期间显示出 T2D 风险升高(RR=1.29 [95% CI 1.08-1.53​​] 和 1.34 [1.13-1.60],分别)。在不同的簇中观察到健康生活方式评分与 T2D 风险之间的负相关性,与簇 1 相比,簇 5 中观察到的关联性更强。在生活方式健康的个体中,簇 5 中的个体与簇 5 中的个体相比,具有相似的 T2D 风险。在集群 1 中(RR=1.03 [0.91-1.18])。这项研究确定了糖尿病前期的遗传亚型,这些亚型在进展为 T2D 的风险和健康生活方式的益处方面有所不同。
更新日期:2024-04-11
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