Kanney Nita, Patki Amit, Chandler-Laney Paula, Garvey W Timothy, Hidalgo Bertha A
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Metabolites. 2022 Dec 7;12(12):1226. doi: 10.3390/metabo12121226.
A known association exists between exposure to gestational diabetes mellitus (GDM) and epigenetic age acceleration (EAA) in GDM-exposed offspring compared to those without GDM exposure. This association has not been assessed previously in mothers with pregnancies complicated by GDM. A total of 137 mother-child dyads with an index pregnancy 4−10 years before study enrollment were included. Clinical data and whole blood samples were collected and quantified to obtain DNA methylation (DNAm) estimates using the Illumina MethylEPIC 850K array in mothers and offspring. DNAm age and age acceleration were evaluated using the Horvath and Hannum clocks. Multivariable linear regression models were performed to determine the association between EAA and leptin, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, and HOMA-IR. Mothers with a GDM and non-GDM pregnancy had strong correlations between chronological age and DNAm age (r > 0.70). Offspring of GDM mothers had moderate to strong correlations, whereas offspring of non-GDM mothers had moderate correlations between chronological age and DNAm age. Association analyses revealed a significant association between EAA and fasting insulin in offspring (FDR < 0.05), while HDL-C was the only metabolic marker significantly associated with EAA in mothers (FDR < 0.05). Mothers in the GDM group had a higher predicted epigenetic age and age acceleration than mothers in the non-GDM group. The association between EAA with elevated fasting insulin in offspring and elevated HDL-C in mothers suggests possible biomarkers that can better elucidate the effects of exposure to a GDM pregnancy and future cardiometabolic outcomes.
与未暴露于妊娠期糖尿病（GDM）的后代相比，暴露于GDM的后代中存在已知的妊娠期糖尿病与表观遗传年龄加速（EAA）之间的关联。此前尚未在患有GDM的妊娠母亲中评估这种关联。本研究纳入了137对母婴二元组，其索引妊娠发生在研究入组前4至10年。收集临床数据和全血样本并进行定量，以使用Illumina MethylEPIC 850K阵列获得母亲和后代的DNA甲基化（DNAm）估计值。使用Horvath和Hannum时钟评估DNAm年龄和年龄加速。进行多变量线性回归模型以确定EAA与瘦素、高密度脂蛋白胆固醇（HDL-C）、空腹血糖、空腹胰岛素和HOMA-IR之间的关联。患有GDM和非GDM妊娠的母亲的实际年龄与DNAm年龄之间存在强相关性（r>0.70）。GDM母亲的后代在实际年龄与DNAm年龄之间存在中度至强相关性，而非GDM母亲的后代则存在中度相关性。关联分析显示后代中EAA与空腹胰岛素之间存在显著关联（FDR<0.05），而HDL-C是母亲中与EAA显著相关的唯一代谢标志物（FDR<0.05）。GDM组的母亲比非GDM组的母亲具有更高的预测表观遗传年龄和年龄加速。后代中EAA与空腹胰岛素升高以及母亲中HDL-C升高之间的关联表明，可能存在更好地阐明暴露于GDM妊娠的影响和未来心脏代谢结局的生物标志物。
