Departments of Medicine, Obstetrics & Gynecology, and Epidemiology, University of Michigan, Ann Arbor, Michigan, USA.
Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Aurora, Aurora, Colorado, USA.
Diabet Med. 2022 Nov;39(11):e14925. doi: 10.1111/dme.14925. Epub 2022 Aug 4.
No reports examine the relationship between in-utero exposure to gestational diabetes mellitus (GDM), offspring epigenetic age acceleration (EAA), and offspring insulin sensitivity.
Using data from a cohort study, we examined associations between GDM in-utero exposure and offspring EAA at approximately 10 years of age, using separate regression models adjusting for offspring chronological age and sex. We also examined associations between EAA with updated homeostasis model assessment of insulin sensitivity and secretion (HOMA2-S and HOMA2-β) measured at approximately 10 and 16 years of age, using mixed linear regression models accounting for repeated measures after adjustment for offspring chronological age and sex.
Compared to unexposed offspring (n = 91), offspring exposed to GDM (n = 88) had greater EAA or older extrinsic age compared to chronological age (β-coefficient 2.00, 95% confidence interval [0.71, 3.28], p = 0.0025), but not greater intrinsic EAA (β-coefficient -0.07, 95% CI [-0.71, 0.57], p = 0.93). Extrinsic EAA was associated with lower insulin sensitivity (β-coefficient -0.018, 95% CI [-0.035, -0.002], p = 0.03) and greater insulin secretion (β-coefficient 0.018, 95% CI [0.006, 0.03], p = 0.003), and these associations persisted after further adjustment for measures of maternal and child adiposity. No associations were observed between intrinsic EAA and insulin sensitivity and secretion, before or after adjustment for measures of maternal and child adiposity.
In this study, children exposed to GDM experience greater extrinsic EAA, which is associated with lower insulin sensitivity and greater insulin secretion. Further studies are needed to determine the directionality of these associations.
目前尚无研究报告探讨宫内暴露于妊娠期糖尿病（GDM）、后代表观遗传年龄加速（EAA）与后代胰岛素敏感性之间的关系。
本研究使用队列研究的数据，通过分别调整后代的实际年龄和性别，在大约 10 岁时使用回归模型来检验 GDM 宫内暴露与后代 EAA 之间的相关性。我们还使用混合线性回归模型，在调整后代实际年龄和性别后，根据大约 10 岁和 16 岁时的稳态模型评估胰岛素敏感性和分泌的更新指标（HOMA2-S 和 HOMA2-β）来检验 EAA 与这些指标之间的相关性。
与未暴露于 GDM 的后代（n=91）相比，暴露于 GDM 的后代（n=88）的 EAA 或外源性年龄比实际年龄大（β系数为 2.00，95%置信区间[0.71，3.28]，p=0.0025），但内源性 EAA 没有差异（β系数为-0.07，95%置信区间[-0.71，0.57]，p=0.93）。外源性 EAA 与较低的胰岛素敏感性（β系数-0.018，95%置信区间[-0.035，-0.002]，p=0.03）和更高的胰岛素分泌（β系数 0.018，95%置信区间[0.006，0.03]，p=0.003）相关，这些相关性在进一步调整母亲和孩子肥胖的指标后仍然存在。在调整母亲和孩子肥胖的指标前后，内源性 EAA 与胰岛素敏感性和分泌均无相关性。
在本研究中，暴露于 GDM 的儿童经历了更大的外源性 EAA，这与较低的胰岛素敏感性和更高的胰岛素分泌有关。需要进一步的研究来确定这些关联的方向。
