How does exposure to overnutrition in utero lead to childhood adiposity? Testing the insulin hypersecretion hypothesis in the EPOCH cohort.
How does exposure to overnutrition in utero lead to childhood adiposity? Testing the insulin hypersecretion hypothesis in the EPOCH cohort.
复制标题
子宫内营养过剩如何导致儿童肥胖？
DOI：
10.1007/s00125-021-05515-2
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发表时间：
2021
期刊：
影响因子：
8.2
通讯作者：
Dabelea,Dana
中科院分区：
文献类型：
--
作者：
Perng,Wei;Kelsey,MeganM;Sauder,KatherineA;Dabelea,Dana
目的/假设我们的目的是探索正常体重儿童子宫内营养过剩与肥胖发展之间的代谢途径。方法我们纳入了312名正常体重的在子宫内暴露或未暴露于营养过剩的青少年（母亲BMI≥25 kg/m2或妊娠糖尿病）。在10岁（基线）和16岁（随访）时分别测定空腹胰岛素、血糖和体成分。我们检查了子宫内营养过剩与基线空腹胰岛素的关系，随后检查了基线空腹胰岛素与肥胖的关系（BMIzscore [BMIZ]、皮下脂肪组织[SAT]、内脏脂肪组织[VAT]）、胰岛素抵抗（HOMA-IR）和随访期间的空腹血糖。结果>所有参与者基线体重正常（BMIZ - 0.32±0.88），暴露与未暴露青年的BMIZ无差异（p= 0.14）。在研究人群中，47.8%为女性，47.4%为白人。即使在控制了VAT/SAT比值后，子宫内营养过剩与基线空腹胰岛素升高14%（几何平均比值1.14 [95% CI 1.01, 1.29]）相对应。较高的基线空腹胰岛素与较高的BMIZ （0.41 [95% CI 0.26, 0.55]）、SAT （13.9 [95% CI 2.4, 25.4] mm2）、VAT （2.0 [95% CI 0.1, 3.8] mm2）、HOMA-IR （0.87 [95% CI 0.68, 1.07]）和空腹血糖（0.23 [95% CI 0.09, 0.38] SD）相对应。结论/解释子宫内营养过剩可能导致儿童期高胰岛素血症，从而导致肥胖。然而，我们的研究从10岁开始，因此没有考虑到营养过剩引起的早期代谢变化。需要对正常体重的青少年进行纵向研究，从生命早期开始，反复测量体重、脂肪分布、胰岛素敏感性、β细胞功能和血糖水平，以阐明与早期暴露于肥胖和血糖异常有关的代谢变化的顺序。图形抽象
Aims/hypothesisOur aim was to explore metabolic pathways linking overnutrition in utero to development of adiposity in normal-weight children.MethodsWe included 312 normal-weight youth exposed or unexposed to overnutrition in utero (maternal BMI ≥25 kg/m2or gestational diabetes). Fasting insulin, glucose and body composition were measured at age ~10 years (baseline) and ~16 years (follow-up). We examined associations of overnutrition in utero with baseline fasting insulin, followed by associations of baseline fasting insulin with adiposity (BMIzscore [BMIZ], subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT]), insulin resistance (HOMA-IR) and fasting glucose during follow-up.Results>All participants were normal weight at baseline (BMIZ −0.32 ± 0.88), with no difference in BMIZ for exposed vs unexposed youth (p= 0.14). Of the study population, 47.8% were female sex and 47.4% were of white ethnicity. Overnutrition in utero corresponded with 14% higher baseline fasting insulin (geometric mean ratio 1.14 [95% CI 1.01, 1.29]), even after controlling for VAT/SAT ratio. Higher baseline fasting insulin corresponded with higher BMIZ (0.41 [95% CI 0.26, 0.55]), SAT (13.9 [95% CI 2.4, 25.4] mm2), VAT (2.0 [95% CI 0.1, 3.8] mm2), HOMA-IR (0.87 [95% CI 0.68, 1.07]) and fasting glucose (0.23 [95% CI 0.09, 0.38] SD).Conclusions/interpretationOvernutrition in utero may result in hyperinsulinaemia during childhood, preceding development of adiposity. However, our study started at age 10 years, so earlier metabolic changes in response to overnutrition were not taken into account. Longitudinal studies in normal-weight youth starting earlier in life, and with repeated measurements of body weight, fat distribution, insulin sensitivity, beta cell function and blood glucose levels, are needed to clarify the sequence of metabolic changes linking early-life exposures to adiposity and dysglycaemia.Graphical abstract