PDF(Pubmed)
Abstract：
BACKGROUND: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease.
METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.
RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3 × 10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.
CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.
METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases.
RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3 × 10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index.
CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.
摘要：
背景：产前暴露于饥荒与代谢性疾病的风险增加有关，包括肥胖和2型糖尿病。我们使用核磁共振（NMR）代谢组学分析来确定与第二次世界大战结束时荷兰饥荒期间产前饥荒暴露生存相关的代谢变化，并随后评估其与疾病的联系。
方法：NMR代谢组学数据来自480名产前暴露于饥荒的个体的血清（平均58.8年，0.5标准差）和464名对照（平均57.9年，5.4标准差）。我们测试了产前饥荒暴露与168个个体代谢生物标志物水平的关联，并比较了饥荒暴露与154个常见疾病的代谢生物标志物特征。
结果：产前饥荒暴露与较高浓度的支链氨基酸（（异）亮氨酸）有关，芳香族氨基酸（酪氨酸），和晚年的葡萄糖(0.2-0.3标准差，p<3×10-3)。产前饥荒暴露的代谢生物标志物特征与英国生物库的2型糖尿病呈正相关（r=0.77，p=3×10-27），当重新估计无糖尿病个体的产前饥荒暴露特征时(r=0.67,p=1×10-18)。值得注意的是,这种关联扩展到有特征的115种常见疾病(0.3≤r≤0.9,p<3.2×10-4).当根据体重指数调整饥荒特征时，饥荒暴露的代谢特征与疾病结局之间的相关性减弱。
结论：产前饥荒暴露与代谢生物标志物特征相关，该特征与多种疾病的特征非常相似。这一观察结果可以部分归因于肥胖的共同参与。
方法：NMR代谢组学数据来自480名产前暴露于饥荒的个体的血清（平均58.8年，0.5标准差）和464名对照（平均57.9年，5.4标准差）。我们测试了产前饥荒暴露与168个个体代谢生物标志物水平的关联，并比较了饥荒暴露与154个常见疾病的代谢生物标志物特征。
结果：产前饥荒暴露与较高浓度的支链氨基酸（（异）亮氨酸）有关，芳香族氨基酸（酪氨酸），和晚年的葡萄糖(0.2-0.3标准差，p<3×10-3)。产前饥荒暴露的代谢生物标志物特征与英国生物库的2型糖尿病呈正相关（r=0.77，p=3×10-27），当重新估计无糖尿病个体的产前饥荒暴露特征时(r=0.67,p=1×10-18)。值得注意的是,这种关联扩展到有特征的115种常见疾病(0.3≤r≤0.9,p<3.2×10-4).当根据体重指数调整饥荒特征时，饥荒暴露的代谢特征与疾病结局之间的相关性减弱。
结论：产前饥荒暴露与代谢生物标志物特征相关，该特征与多种疾病的特征非常相似。这一观察结果可以部分归因于肥胖的共同参与。
