Harrall Kylie K, Glueck Deborah H, Lange Leslie A, Litkowski Elizabeth M, Vanderlinden Lauren A, Konigsberg Iain R, Cree Melanie G, Perng Wei, Dabelea Dana
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus, Aurora, CO.
Department of Health Outcomes and Biomedical Informatics, University of Florida College of Medicine, Gainesville, FL.
Diabetes Care. 2025 Jul 1;48(7):1280-1287. doi: 10.2337/dc25-0194.
Exposure to maternal gestational diabetes mellitus (GDM) is associated with childhood BMI. Among youth, we explored whether three different glucagon-like peptide 1 receptor gene (GLP-1R) polymorphisms modified the associations between 1) GDM and BMI trajectories and 2) GDM and markers of glucose-insulin homeostasis.
For 464 participants from the Exploring Perinatal Outcomes Among Children (EPOCH) study, microarray genotyping was performed during childhood (∼10 years). BMI trajectories across childhood and adolescence were characterized using repeated measurements from research visits and medical record abstraction. Markers of glucose-insulin homeostasis were derived from one oral glucose tolerance test in adolescence (∼16 years). Linear models assessed effect modification by GLP-1R polymorphisms.
Among youth with at least one minor allele of rs10305420 (CT or TT) or rs1042044 (CA or AA), but not among major allele homozygotes, exposure to GDM was associated with higher average BMI. For rs6923761, participants who were exposed to GDM and were major allele homozygotes (i.e., genotype GG) had significantly higher average BMI than all other participants in the cohort. No polymorphisms modified the association between GDM and markers of glucose-insulin homeostasis during adolescence.
GLP-1R polymorphisms modify the association between GDM and BMI growth among youth. Further studies are needed to replicate these findings, and to better understand the mechanisms by which GLP-1R polymorphisms lead to heterogeneity in offspring BMI growth.
母亲妊娠期糖尿病（GDM）与儿童期体重指数（BMI）相关。在青少年中，我们探讨了三种不同的胰高血糖素样肽1受体基因（GLP-1R）多态性是否改变了1）GDM与BMI轨迹之间以及2）GDM与葡萄糖-胰岛素稳态标志物之间的关联。
对于来自儿童围产期结局探索（EPOCH）研究的464名参与者，在儿童期（约10岁）进行了微阵列基因分型。利用研究访视和病历摘要中的重复测量来描述儿童期和青少年期的BMI轨迹。葡萄糖-胰岛素稳态标志物来自青少年期（约16岁）的一次口服葡萄糖耐量试验。线性模型评估GLP-1R多态性的效应修饰作用。
在至少携带rs10305420（CT或TT）或rs1042044（CA或AA）至少一个次要等位基因的青少年中，而非主要等位基因纯合子中，暴露于GDM与较高的平均BMI相关。对于rs6923761，暴露于GDM且为主要等位基因纯合子（即基因型GG）的参与者的平均BMI显著高于队列中的所有其他参与者。在青少年期，没有多态性改变GDM与葡萄糖-胰岛素稳态标志物之间的关联。
GLP-1R多态性改变了青少年中GDM与BMI增长之间的关联。需要进一步研究来重复这些发现，并更好地理解GLP-1R多态性导致后代BMI增长异质性的机制。
