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妊娠期间母体葡萄糖调节异常与儿童期和青春期后代肥胖、胰岛素抵抗和脂肪因子标志物的相关性研究。

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence.

机构信息

The George Washington University School of Medicine and Health Sciences, Washington, DC.

Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.

出版信息

J Pediatr. 2024 Sep;272:114100. doi: 10.1016/j.jpeds.2024.114100. Epub 2024 May 15.

Abstract

OBJECTIVE

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence.

STUDY DESIGN

Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI).

RESULTS

In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI.

CONCLUSION

Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

摘要

目的

研究妊娠期间母体葡萄糖调节异常与后代儿童期和青春期肥胖、胰岛素抵抗、脂肪因子和炎症标志物的相关性。

研究设计

Viva 项目是一项前瞻性产前队列研究(n=2128 例活产儿),于 1999 年至 2002 年在美国马萨诸塞州东部启动。在妊娠中期,临床医生使用两步口服葡萄糖挑战试验筛查妊娠期糖尿病。在后代中,我们在儿童中期(n=1107)、青少年早期(n=1027)和青少年中期(n=693)测量了人体测量学、胰岛素抵抗、脂肪因子、脂质和炎症标志物。我们使用多变量线性回归模型和广义估计方程,根据儿童年龄和性别、母亲年龄、种族/民族、教育程度、产次和怀孕期间吸烟情况进行调整;我们还根据孕前体重指数(BMI)进行了调整。

结果

在青少年中期(17.1[0.8]岁),患有妊娠期糖尿病的母亲的后代(n=27)的 BMI z 评分(β;95%可信区间;0.41 SD;0.00,0.82)、皮褶厚度总和(8.15mm;2.48,13.82)、胰岛素抵抗的稳态模型评估(0.81 单位;0.13,1.50)、瘦素 z 评分(0.40 SD;0.01,0.78)和瘦素/脂联素比值 z 评分(0.51 SD;CI 0.09,0.93)高于血糖正常母亲的后代(多变量调整模型)。与更早的时间点相比,在青少年中期,与 BMI、胰岛素抵抗的稳态模型评估和脂联素的相关性更强。在校正母亲孕前 BMI 后,相关性向零值减弱。

结论

妊娠期糖尿病的暴露与青少年中期的肥胖、胰岛素抵抗和脂肪因子的改变有关。我们的研究结果表明,青春期可能是胎儿编程代谢异常出现的关键时期。

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