Aims/hypothesis

Our aim was to explore metabolic pathways linking overnutrition in utero to development of adiposity in normal-weight children.

Methods

We included 312 normal-weight youth exposed or unexposed to overnutrition in utero (maternal BMI ≥25 kg/m² or 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 (BMI z score [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/interpretation

Overnutrition 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

中文翻译：

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子宫内营养过剩如何导致儿童肥胖？在 EPOCH 队列中检验胰岛素分泌过多假说

目标/假设

我们的目的是探索将子宫内营养过剩与正常体重儿童肥胖发展联系起来的代谢途径。

方法

我们纳入了 312 名在子宫内暴露或未暴露于营养过剩（母亲 BMI ≥25 kg/m ²或妊娠糖尿病）的正常体重青年。在约 10 岁（基线）和约 16 岁（随访）时测量空腹胰岛素、葡萄糖和身体成分。我们检查了子宫内营养过剩与基线空腹胰岛素的关系，然后是基线空腹胰岛素与肥胖（BMI z评分 [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

>所有参与者在基线时体重均正常 (BMIZ -0.32 ± 0.88)，暴露与未暴露青年的 BMIZ 没有差异 ( 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 比率后，子宫内营养过剩与基线空腹胰岛素升高 14% 相对应（几何平均比率 1.14 [95% CI 1.01, 1.29]）。较高的基线空腹胰岛素对应于较高的 BMIZ (0.41 [95% CI 0.26, 0.55])、SAT (13.9 [95% CI 2.4, 25.4] mm ² )、VAT (2.0 [95% CI 0.1, 3.8] mm ² )、 HOMA-IR (0.87 [95% CI 0.68, 1.07]) 和空腹血糖 (0.23 [95% CI 0.09, 0.38] SD)。

结论/解释

子宫内营养过剩可能导致儿童期高胰岛素血症，先于肥胖的发展。然而，我们的研究始于 10 岁，因此未考虑早期因营养过剩而发生的代谢变化。需要在生命早期开始对体重正常的青年进行纵向研究，并反复测量体重、脂肪分布、胰岛素敏感性、β细胞功能和血糖水平，以阐明将生命早期暴露与肥胖联系起来的代谢变化顺序和血糖异常。

图形概要