Ravelli A C, van der Meulen J H, Michels R P, Osmond C, Barker D J, Hales C N, Bleker O P
Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Netherlands.
Lancet. 1998 Jan 17;351(9097):173-7. doi: 10.1016/s0140-6736(97)07244-9.
Reduced growth in utero is associated with type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance in adult life. There is no direct evidence in human beings that maternal nutrition during gestation affects insulin-glucose metabolism. We investigated glucose tolerance in people born around the time of famine in the Netherlands during 1944-45.
We included 702 people born between Nov 1, 1943, and Feb 28, 1947, in Amsterdam, for whom we had detailed prenatal and birth records. We compared glucose and insulin responses to a standard oral glucose load in participants exposed to famine at any stage during gestation (exposed participants) with those who were born in the year before or conceived in the year after the famine (non-exposed participants).
Glucose concentrations were increased 2 h after a standard glucose load among exposed participants (p = 0.006), and were highest in men and women exposed during mid and late gestation. Mean 2 h glucose concentration among non-exposed participants was 5.8 mmol/L; concentrations were 0.5 mmol/L (95% CI 0.1-0.9) higher among participants exposed during late gestation, 0.4 mmol/L (0-0.8) higher among those exposed during mid gestation, and 0.1 mmol/L (-0.4 to 0.6) among those exposed during early gestation. Participants born as thin babies to mothers with low bodyweights had the highest concentrations and concentrations were especially high among people exposed to famine who became obese as adults. Prenatal exposure to famine was related to increased fasting proinsulin (p = 0.05) and 2 h insulin concentrations (p = 0.04), which suggests an association with insulin resistance.
Prenatal exposure to famine, especially during late gestation, is linked to decreased glucose tolerance in adults. Poor nutrition in utero may lead to permanent changes in insulin-glucose metabolism, even if the effect on fetal growth is small. This effect of famine on glucose tolerance is especially important in people who become obese.
子宫内生长受限与2型（非胰岛素依赖型）糖尿病及成年期糖耐量受损有关。尚无直接证据表明人类孕期的母体营养会影响胰岛素-葡萄糖代谢。我们对1944年至1945年荷兰饥荒时期前后出生的人群的糖耐量进行了调查。
我们纳入了1943年11月1日至1947年2月28日在阿姆斯特丹出生的702人，这些人有详细的产前和出生记录。我们比较了孕期任何阶段暴露于饥荒的参与者（暴露组参与者）与在饥荒前一年出生或在饥荒后一年受孕的参与者（非暴露组参与者）对标准口服葡萄糖负荷的葡萄糖和胰岛素反应。
暴露组参与者在标准葡萄糖负荷后2小时血糖浓度升高（p = 0.006），在孕中期和晚期暴露的男性和女性中最高。非暴露组参与者的平均2小时血糖浓度为5.8 mmol/L；孕晚期暴露的参与者浓度高0.5 mmol/L（95%CI 0.1 - 0.9），孕中期暴露的参与者高0.4 mmol/L（0 - 0.8），孕早期暴露的参与者高0.1 mmol/L（-0.4至0.6）。出生时体重低的瘦婴儿的母亲所生的参与者血糖浓度最高，在成年后肥胖的饥荒暴露人群中浓度尤其高。产前暴露于饥荒与空腹胰岛素原升高（p = 0.05）和2小时胰岛素浓度升高（p = 0.04）有关，这表明与胰岛素抵抗有关。
产前暴露于饥荒，尤其是在孕晚期，与成年人糖耐量降低有关。子宫内营养不良可能导致胰岛素-葡萄糖代谢的永久性变化，即使对胎儿生长的影响很小。饥荒对糖耐量的这种影响在肥胖人群中尤为重要。
