Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
Diabetologia. 2021 Jan;64(1):83-94. doi: 10.1007/s00125-020-05294-2. Epub 2020 Oct 6.
AIMS/HYPOTHESIS: The aim of this work was to investigate the association of maternal HbA during mid-pregnancy with biomarkers of glucose-insulin homeostasis during early childhood (4-7 years of age) and to assess whether and how offspring adiposity at birth and at age 4-7 years mediates this relationship among 345 mother-child pairs in the Healthy Start Study.
The exposure was maternal HbA (mmol/mol) measured at 20-34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4-7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4-7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex.
There was a significant total effect of maternal HbA on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA and offspring glucose (p trend <0.001), and an inverse trend across tertiles of HbA and offspring 1/insulin (p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI -0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4-7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage.
CONCLUSIONS/INTERPRETATION: Offspring of women with higher HbA during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity. Graphical abstract.
目的/假设：本研究旨在调查妊娠中期母体血红蛋白 A1c（HbA）与儿童早期（4-7 岁）葡萄糖-胰岛素稳态生物标志物之间的关联，并评估在 345 对母子对的健康启动研究中，出生时和 4-7 岁时后代的肥胖程度是否以及如何调节这种关系。
暴露因素为妊娠 20-34 周时测量的母体 HbA（mmol/mol），并分为三部分。结果为儿童 4-7 岁时的空腹血糖、1/胰岛素、HOMA2-IR 和 HOMA2-B。中介变量为出生时的脂肪百分比（%FM）、4-7 岁时的%FM 以及两者之和作为累积肥胖的指标。中介分析采用基于反事实的方法进行。所有模型均考虑了母亲的种族/民族、后代的年龄和性别。
母体 HbA 对后代血糖和 1/胰岛素有显著的总效应。具体来说，我们观察到 HbA 三分位与后代血糖呈正相关趋势（p 趋势 <0.001），HbA 三分位与后代 1/胰岛素呈负相关趋势（p 趋势 =0.04）。例如，与 HbA 最低三分位母亲的后代相比，HbA 第二和第三三分位母亲的后代在 4-7 岁时的空腹血糖浓度分别高 0.04mmol/l（95%CI -0.05, 0.13）和 0.17mmol/l（95%CI 0.08, 0.26）。调整孕前 BMI 后，结果并未明显改变。我们没有发现任何证据表明后代在任何生命阶段的肥胖程度存在中介作用。
结论/解释：妊娠期间母体 HbA 较高的后代在儿童早期时空腹血糖较高，胰岛素敏感性较低。这些关系在很大程度上不受儿童自身肥胖的影响。图表摘要。
