| Title: | Longitudinal association of cumulative risk factors in early life, genetic risk, and healthy lifestyles during adulthood with the risk of type 2 diabetes |
| Journal: | BMC Medicine |
| Published: | 23 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40269887/ |
| DOI: | https://doi.org/10.1186/s12916-025-04025-x |
| URL: | https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-025-04025-x |
Publication 15776
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Abstract
BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionsEarly-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>
14 Keywords
- Adult
- Aged
- Diabetes Mellitus, Type 2
- Female
- Genetic Predisposition to Disease
- Healthy Lifestyle
- Humans
- Longitudinal Studies
- Male
- Middle Aged
- Pregnancy
- Risk Factors
- Smoking
- United Kingdom
12 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
1 Application
| Application ID | Title |
|---|---|
| 173828 | Life-course risk factors and development of chronic diseases and cancer: multi-omics analyses |
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