Jiajin Hu, Honghao Yang, Yilin Liu, Lu Zheng, Xiaoyan Zhang, Jing Yang, Zhe Yang, Xiaochuan Wang, Borui Liu, Hong Cui, Izzuddin M Aris, Yang Xia
{"title":"早期累积风险因素、遗传风险和成年期健康生活方式与2型糖尿病风险的纵向关联","authors":"Jiajin Hu, Honghao Yang, Yilin Liu, Lu Zheng, Xiaoyan Zhang, Jing Yang, Zhe Yang, Xiaochuan Wang, Borui Liu, Hong Cui, Izzuddin M Aris, Yang Xia","doi":"10.1186/s12916-025-04025-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The combined influence of early life risk factors on the type 2 diabetes (T2D) development is not well-studied, and it is unclear whether these associations can by modified by genetic risk and healthy lifestyles in later life.</p><p><strong>Methods: </strong>We studied 148,621 participants in the UK Biobank. We calculated early-life risk scores (ERS) by summing the cumulative number of three early-life risk factors: low birth weight, maternal smoking during pregnancy, and non-breastfed as a baby. We estimated polygenic risk scores (PRS) for T2D and calculated participants' modifiable healthy lifestyle score (MHS) during adulthood.</p><p><strong>Results: </strong>A total of 7,408 incident T2D were identified. ERS showed a positive dose-response association with T2D risk. Compared with participants with 0 ERS, those with 3 ERS had the highest risk of developing T2D (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.65, 2.26). This association was not modified by T2D-PRS or MHS. In the joint exposure analyses, compared with participants with the lowest risk exposure (i.e., lowest ERS combined with lowest T2D-PRS/healthy lifestyle in later life), we observed highest risk of T2D among individuals with the highest ERS combined with the highest tertile of T2D-PRS (HR = 6.67, 95% CI: 5.43, 8.20) or an unhealthy lifestyle in later life (HR = 4.99, 95% CI: 3.54, 7.02), respectively.</p><p><strong>Conclusions: </strong>Early-life risk factors are associated with a higher risk of T2D in a dose-response manner, regardless of genetic risk or later-life healthy lifestyle. Therefore, identifying early-life modifiable risk factors is helpful to develop strategies of T2D prevention.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"23 1","pages":"239"},"PeriodicalIF":7.0000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020231/pdf/","citationCount":"0","resultStr":"{\"title\":\"Longitudinal association of cumulative risk factors in early life, genetic risk, and healthy lifestyles during adulthood with the risk of type 2 diabetes.\",\"authors\":\"Jiajin Hu, Honghao Yang, Yilin Liu, Lu Zheng, Xiaoyan Zhang, Jing Yang, Zhe Yang, Xiaochuan Wang, Borui Liu, Hong Cui, Izzuddin M Aris, Yang Xia\",\"doi\":\"10.1186/s12916-025-04025-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The combined influence of early life risk factors on the type 2 diabetes (T2D) development is not well-studied, and it is unclear whether these associations can by modified by genetic risk and healthy lifestyles in later life.</p><p><strong>Methods: </strong>We studied 148,621 participants in the UK Biobank. We calculated early-life risk scores (ERS) by summing the cumulative number of three early-life risk factors: low birth weight, maternal smoking during pregnancy, and non-breastfed as a baby. We estimated polygenic risk scores (PRS) for T2D and calculated participants' modifiable healthy lifestyle score (MHS) during adulthood.</p><p><strong>Results: </strong>A total of 7,408 incident T2D were identified. ERS showed a positive dose-response association with T2D risk. Compared with participants with 0 ERS, those with 3 ERS had the highest risk of developing T2D (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.65, 2.26). This association was not modified by T2D-PRS or MHS. In the joint exposure analyses, compared with participants with the lowest risk exposure (i.e., lowest ERS combined with lowest T2D-PRS/healthy lifestyle in later life), we observed highest risk of T2D among individuals with the highest ERS combined with the highest tertile of T2D-PRS (HR = 6.67, 95% CI: 5.43, 8.20) or an unhealthy lifestyle in later life (HR = 4.99, 95% CI: 3.54, 7.02), respectively.</p><p><strong>Conclusions: </strong>Early-life risk factors are associated with a higher risk of T2D in a dose-response manner, regardless of genetic risk or later-life healthy lifestyle. Therefore, identifying early-life modifiable risk factors is helpful to develop strategies of T2D prevention.</p>\",\"PeriodicalId\":9188,\"journal\":{\"name\":\"BMC Medicine\",\"volume\":\"23 1\",\"pages\":\"239\"},\"PeriodicalIF\":7.0000,\"publicationDate\":\"2025-04-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020231/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12916-025-04025-x\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12916-025-04025-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Longitudinal association of cumulative risk factors in early life, genetic risk, and healthy lifestyles during adulthood with the risk of type 2 diabetes.
Background: The combined influence of early life risk factors on the type 2 diabetes (T2D) development is not well-studied, and it is unclear whether these associations can by modified by genetic risk and healthy lifestyles in later life.
Methods: We studied 148,621 participants in the UK Biobank. We calculated early-life risk scores (ERS) by summing the cumulative number of three early-life risk factors: low birth weight, maternal smoking during pregnancy, and non-breastfed as a baby. We estimated polygenic risk scores (PRS) for T2D and calculated participants' modifiable healthy lifestyle score (MHS) during adulthood.
Results: A total of 7,408 incident T2D were identified. ERS showed a positive dose-response association with T2D risk. Compared with participants with 0 ERS, those with 3 ERS had the highest risk of developing T2D (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.65, 2.26). This association was not modified by T2D-PRS or MHS. In the joint exposure analyses, compared with participants with the lowest risk exposure (i.e., lowest ERS combined with lowest T2D-PRS/healthy lifestyle in later life), we observed highest risk of T2D among individuals with the highest ERS combined with the highest tertile of T2D-PRS (HR = 6.67, 95% CI: 5.43, 8.20) or an unhealthy lifestyle in later life (HR = 4.99, 95% CI: 3.54, 7.02), respectively.
Conclusions: Early-life risk factors are associated with a higher risk of T2D in a dose-response manner, regardless of genetic risk or later-life healthy lifestyle. Therefore, identifying early-life modifiable risk factors is helpful to develop strategies of T2D prevention.
期刊介绍：
BMC Medicine is an open access, transparent peer-reviewed general medical journal. It is the flagship journal of the BMC series and publishes outstanding and influential research in various areas including clinical practice, translational medicine, medical and health advances, public health, global health, policy, and general topics of interest to the biomedical and sociomedical professional communities. In addition to research articles, the journal also publishes stimulating debates, reviews, unique forum articles, and concise tutorials. All articles published in BMC Medicine are included in various databases such as Biological Abstracts, BIOSIS, CAS, Citebase, Current contents, DOAJ, Embase, MEDLINE, PubMed, Science Citation Index Expanded, OAIster, SCImago, Scopus, SOCOLAR, and Zetoc.
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