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生命早期饥荒暴露对老年代谢功能障碍相关脂肪性肝病(MASLD)风险的影响——基于有向无环图模型的横断面研究
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Abstract:
背景：生命早期饥荒暴露会导致代谢综合征和脂肪肝病，但对最新定义的代谢功能障碍相关脂肪性肝病(MASLD)风险的影响暂不清楚。本研究的目的是通过因果定向无环图(DAG)分析生命早期饥荒暴露MASLD患病风险的影响。方法：分析了重庆市某体检中心15,791例含腹部超声检查体检对象的数据。将研究对象按出生年份分为(1953年1月1日至1955年12月31日出生)、童年晚期暴露组(1956年1月1日至1958年12月31日出生)、幼儿暴露组、胎儿暴露组(1959年1月1日至1961年12月31日出生)和非暴露组(1962年1月1日至1964年12月31出生)。通过DAG模型获得无偏调整集。使用二元logistic和线性回归模型对结果进行调整。结果：本研究人群中MASLD患病率为38.1%。但男性和女性受饥荒暴露人群的MASLD患病风险相反。相比于非暴露组，男性胎儿饥荒暴露组(OR = 0.688, 95% CI: [0.608, 0.779], P = 0.000)和幼儿饥荒暴露组(OR = 0.673, 95% CI: [0.593, 0.764], P = 0.000)和童年晚期暴露组(OR = 0.628, 95% CI: [0.537, 0.735], P = 0.000)患MASLD风险较低。而女性的童年晚期暴露组患MASLD的风险是非暴露组约1.2倍(OR = 1.236, 95% CI: [1.089, 1.404], P = 0.001)。早年经历饥荒男性的BMI、甘油三酯(TG)和高密度脂蛋白(HDL)指标的心血管代谢相关风险都较低，而经历饥荒女性的空腹血糖较高。结论：生命早期暴露于饥荒可能会降低男性老年时患MASLD的风险，但女性在童年晚期经历饥荒可能会增加老年时MASLD的风险，不同性别的风险差异可能是由于饥荒经历对男性和女性心血管代谢风险因素相关指标的影响不同所造成的。本研究与过往研究的差异可能是由于地区间受灾程度差异和研究对象的年龄阶段不同导致的，需要进一步的队列研究探索饥荒暴露对MASLD的长期影响。
Background: Early life famine exposure leads to metabolic syndrome and fatty liver disease, but the effect on the risk of newly defined metabolic dysfunction-associated fatty liver disease (MASLD) is unclear. The aim of this study was to analyze the impact of early life famine exposure to MASLD risk by causally oriented acyclic graph (DAG). Methods: The data of 15,791 subjects with abdominal ultrasound examination in a physical examination center in Chongqing were analyzed. Participants were divided into (born between January 1, 1953 and December 31, 1955), late childhood exposure group (born between January 1, 1956 and December 31, 1958), infant exposure group, fetal exposure group (born between January 1, 1959 and December 31, 1961) and non-exposure group (born between January 1, 1962 and December 31, 1964). The unbiased adjustment set was obtained by the DAG model. The results were adjusted using binary logistic and linear regression models. Results: The prevalence of MASLD in this population was 38.1%. However, men and women have opposite risks of MASLD in people exposed to famine. Compared with the non-exposure group, the risk of MASLD was lower in the male fetal famine exposure group (OR = 0.688, 95%CI: [0.608 to 0.779], P = 0.000) and the infant famine exposure group (OR = 0.673, 95% CI: 0.593 to 0.764, P = 0.000) and late childhood exposure group (OR = 0.628, 95% CI: [0.537 to 0.735], P = 0.000). The risk of MASLD in the late childhood exposure group of female was about 1.2 times higher than that in the non-exposure group (OR = 1.236, 95% CI: [1.089 to 1.404], P = 0.001). Men who experienced famine early in life
| [1] | Man, S., Deng, Y., Ma, Y., Fu, J., Bao, H., Yu, C., et al. (2023) Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study with 5.7 Million Adults in China. Gastroenterology, 165, 1025-1040. https://doi.org/10.1053/j.gastro.2023.05.053 |
| [2] | 中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版) [J]. 中华肝脏病杂志, 2024, 32(5): 418-434. |
| [3] | Gillman, M.W. (2005) Developmental Origins of Health and Disease. New England Journal of Medicine, 353, 1848-1850. https://doi.org/10.1056/nejme058187 |
| [4] | van Zutphen, T., Ciapaite, J., Bloks, V.W., Ackereley, C., Gerding, A., Jurdzinski, A., et al. (2016) Malnutrition-associated Liver Steatosis and ATP Depletion Is Caused by Peroxisomal and Mitochondrial Dysfunction. Journal of Hepatology, 65, 1198-1208. https://doi.org/10.1016/j.jhep.2016.05.046 |
| [5] | Li, M., Reynolds, C.M., Segovia, S.A., Gray, C. and Vickers, M.H. (2015) Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life. BioMed Research International, 2015, Article ID: 437107. https://doi.org/10.1155/2015/437107 |
| [6] | Smil, V. (1999) China’s Great Famine: 40 Years Later. BMJ, 319, 1619-1621. https://doi.org/10.1136/bmj.319.7225.1619 |
| [7] | National Bureau of Statistics of China (1988) People’s Republic of China Population Statistics Compilation 1949-1985. |
| [8] | Wang, Y., Wang, X., Kong, Y., Zhang, J.H. and Zeng, Q. (2010) The Great Chinese Famine Leads to Shorter and Overweight Females in Chongqing Chinese Population after 50 Years. Obesity, 18, 588-592. https://doi.org/10.1038/oby.2009.296 |
| [9] | Liu, D., Yu, D., Zhao, L., Fang, H., Zhang, J., Wang, J., et al. (2019) Exposure to Famine during Early Life and Abdominal Obesity in Adulthood: Findings from the Great Chinese Famine during 1959-1961. Nutrients, 11, Article 903. https://doi.org/10.3390/nu11040903 |
| [10] | Fang, Z., Chen, C., Wang, H. and Tang, K. (2020) Association between Fetal Exposure to Famine and Anthropometric Measures in Adulthood: A Regression Discontinuity Approach. Obesity, 28, 962-969. https://doi.org/10.1002/oby.22760 |
| [11] | Xu, Y., Yi, Q., Shan, S., Zhou, J., Li, S., Hou, L., et al. (2022) Chinese Famine Exposure in Early Life and Metabolic Obesity Phenotype in Middle Age: Results from the China Health and Retirement Longitudinal Study. Frontiers in Endocrinology, 13, Article 975824. https://doi.org/10.3389/fendo.2022.975824 |
| [12] | Li, Y., Jaddoe, V.W., Qi, L., He, Y., Wang, D., Lai, J., et al. (2011) Exposure to the Chinese Famine in Early Life and the Risk of Metabolic Syndrome in Adulthood. Diabetes Care, 34, 1014-1018. https://doi.org/10.2337/dc10-2039 |
| [13] | Wang, Z., Li, C., Yang, Z., Ma, J. and Zou, Z. (2017) Fetal and Infant Exposure to Severe Chinese Famine Increases the Risk of Adult Dyslipidemia: Results from the China Health and Retirement Longitudinal Study. BMC Public Health, 17, Article No. 488. https://doi.org/10.1186/s12889-017-4421-6 |
| [14] | Xin, X., Wang, W., Xu, H., Li, Z. and Zhang, D. (2018) Exposure to Chinese Famine in Early Life and the Risk of Dyslipidemia in Adulthood. European Journal of Nutrition, 58, 391-398. https://doi.org/10.1007/s00394-017-1603-z |
| [15] | Liu, J., Wang, G., Wu, Y., Guan, Y., Luo, Z., Zhao, G., et al. (2021) Early-Life Exposure to Famine and Risk of Metabolic Associated Fatty Liver Disease in Chinese Adults. Nutrients, 13, Article 4063. https://doi.org/10.3390/nu13114063 |
| [16] | Zhang, Y., Pu, J., Ding, Y., Wu, L., Yin, Y., Sun, M., et al. (2022) Sex Differences at Early Old Stage in Glycolipid Metabolism and Fatty Liver in Offspring Prenatally Exposed to Chinese Great Famine. Frontiers in Nutrition, 9, Article 913966. https://doi.org/10.3389/fnut.2022.913966 |
| [17] | Wang, Y., Zhang, K., Wang, B., Yu, B., Zhang, Z., Yu, Y., et al. (2025) Early-Life Famine Exposure, Genetic Susceptibility and Risk of MAFLD in Adulthood. The Journal of Nutrition, Health and Aging, 29, Article ID: 100443. https://doi.org/10.1016/j.jnha.2024.100443 |
| [18] | Chen, J., Peng, B., Tang, L., Sun, R., Hu, S., Wen, X., et al. (2015) Fetal and Infant Exposure to the Chinese Famine Increases the Risk of Fatty Liver Disease in Chongqing, China. Journal of Gastroenterology and Hepatology, 31, 200-205. https://doi.org/10.1111/jgh.13044 |
| [19] | Greenland, S. (2003) Quantifying Biases in Causal Models: Classical Confounding vs Collider-Stratification Bias. Epidemiology, 14, 300-306. https://doi.org/10.1097/01.ede.0000042804.12056.6c |
| [20] | Lipsky, A.M. and Greenland, S. (2022) Causal Directed Acyclic Graphs. JAMA, 327, 1083-1084. https://doi.org/10.1001/jama.2022.1816 |
| [21] | 中华医学会超声医学分会, 中国研究型医院学会肿瘤介入专业委员会, 国家卫生和健康委员会能力建设和继续教育中心超声医学专家委员会. 肝病超声诊断指南[J]. 中华肝脏病杂志, 2021, 29(5): 385-402. |
| [22] | Rinella, M.E., Lazarus, J.V., Ratziu, V., Francque, S.M., Sanyal, A.J., Kanwal, F., et al. (2023) A Multisociety Delphi Consensus Statement on New Fatty Liver Disease Nomenclature. Journal of Hepatology, 79, 1542-1556. https://doi.org/10.1016/j.jhep.2023.06.003 |
| [23] | Textor, J., van der Zander, B., Gilthorpe, M.S., Liśkiewicz, M. and Ellison, G.T.H. (2017) Robust Causal Inference Using Directed Acyclic Graphs: The R Package ‘Dagitty’. International Journal of Epidemiology, 45, 1887-1894. https://doi.org/10.1093/ije/dyw341 |
| [24] | Miao, W., Geng, Z. and Tchetgen Tchetgen, E.J. (2018) Identifying Causal Effects with Proxy Variables of an Unmeasured Confounder. Biometrika, 105, 987-993. https://doi.org/10.1093/biomet/asy038 |
| [25] | Hair, N.L., Hanson, J.L., Wolfe, B.L. and Pollak, S.D. (2015) Association of Child Poverty, Brain Development, and Academic Achievement. JAMA Pediatrics, 169, 822-829. https://doi.org/10.1001/jamapediatrics.2015.1475 |
| [26] | Paciorek, C.J., Stevens, G.A., Finucane, M.M. and Ezzati, M. (2013) Children’s Height and Weight in Rural and Urban Populations in Low-Income and Middle-Income Countries: A Systematic Analysis of Population-Representative Data. The Lancet Global Health, 1, e300-e309. https://doi.org/10.1016/s2214-109x(13)70109-8 |
| [27] | Alberti, K.G.M.M., Eckel, R.H., Grundy, S.M., Zimmet, P.Z., Cleeman, J.I., Donato, K.A., et al. (2009) Harmonizing the Metabolic Syndrome. Circulation, 120, 1640-1645. https://doi.org/10.1161/circulationaha.109.192644 |
| [28] | Qin, L.L., Luo, B.A., Gao, F., Feng, X.L. and Liu, J.H. (2020) Effect of Exposure to Famine during Early Life on Risk of Metabolic Syndrome in Adulthood: A Meta-Analysis. Journal of Diabetes Research, 2020, Article ID: 3251275. |
| [29] | Yu, C., Wang, J., Wang, F., Han, X., Hu, H., Yuan, J., et al. (2018) Victims of Chinese Famine in Early Life Have Increased Risk of Metabolic Syndrome in Adulthood. Nutrition, 53, 20-25. https://doi.org/10.1016/j.nut.2017.12.013 |
| [30] | Wang, Z., Zou, Z., Wang, S., Yang, Z. and Ma, J. (2018) Chinese Famine Exposure in Infancy and Metabolic Syndrome in Adulthood: Results from the China Health and Retirement Longitudinal Study. European Journal of Clinical Nutrition, 73, 724-732. https://doi.org/10.1038/s41430-018-0211-1 |
| [31] | Yan, S., Hou, W., Wu, H., Jiang, W., Li, Y., Zhang, Y., et al. (2020) Prenatal Exposure to the Chinese Famine and the Risk of Metabolic Syndrome in Adulthood across Consecutive Generations. European Journal of Clinical Nutrition, 74, 1229-1236. https://doi.org/10.1038/s41430-020-0561-3 |
| [32] | Peng, Y., Hai, M., Li, P. and Chen, Y. (2020) Association of Exposure to Chinese Famine in Early Life with the Risk of Metabolic Syndrome in Adulthood. Annals of Nutrition and Metabolism, 76, 140-146. https://doi.org/10.1159/000507356 |
