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Life-course associations of early-life risk factors, modifiable adult lifestyles, and transitions of cardiometabolic disease and multimorbidity: A prospective cohort study

In brief

Early-life risks and unhealthy habits doubled risk of first cardiometabolic disease

In 174,718 UK adults followed for a median 14.6 years, those with at least two early-life risks and an unhealthy adult lifestyle had about twice the risk of developing a first cardiometabolic disease, including stroke, heart disease, or type 2 diabetes. Healthier lifestyles were linked to weaker associations, but the observational study cannot show that lifestyle changes reverse early-life risks.

Journal
The American journal of clinical nutrition (Q1)
Published
1 October 2026
Study design
Prospective / inception cohort
Evidence level
Level 2, Moderate (CEBM 2b)
Authors
Xiaoyan Zhang, Baiwei Xu, Cheng Peng, Huan Li, Kai Yang, Ao Shen, et al.
PMID
42869714
DOI
10.1016/j.ajcnut.2026.101486

Why clinicians should know about it

  • Picked for Epidemiology (paper of the day, 15 October 2026): UK Biobank prospective cohort of early‑life risk and cardiometabolic transitions

Abstract

BACKGROUND: Whether associations of early-life risk factors with cardiometabolic disease (CMD) transitions vary by adult lifestyles remains unclear. OBJECTIVES: We aimed to examine the associations between early-life risk factors and CMD transitions, and to assess whether adult lifestyles can modify these associations. METHODS: We analyzed data from 174,718 adults participating in the United Kingdom Biobank prospective cohort study. We defined 5 CMD transitions using a multistate model: from CMD-free to first CMD (FCMD; including stroke, ischemic heart disease, and type 2 diabetes), from FCMD to cardiometabolic multimorbidity (CMM), and from CMD-free, FCMD, and CMM to death. An early-life risk score (ERS; 0-3) summed low birth weight, maternal smoking around birth, and absence of human milk feeding in infancy. Adult lifestyle was quantified using an adult lifestyle score (ALS) adapted from 4 behavioral metrics of the Life's Essential 8 framework, and data were collected at study enrollment when participants had a median age of 55 y. RESULTS: During a median follow-up of 14.6 y, individuals with both high early-life risk (ERS ≥2) and an unhealthy adult lifestyle (ALS: 0-49) had the highest risks for most adverse transitions, including CMD-free to FCMD [hazard ratio (HR): 2.04; 95% confidence interval (CI): 1.89, 2.21], FCMD to CMM (HR: 1.46; 95% CI: 1.27, 1.69), CMD-free to death (HR: 2.31; 95% CI: 1.95, 2.72), and FCMD to death (HR: 1.64; 95% CI: 1.34, 2.01). The associations of ERS with the risk of most CMD transitions were less pronounced among participants with a healthy adult lifestyle than among those with an unhealthy adult lifestyle. CONCLUSIONS: Joint exposure to adverse early-life experiences and an unhealthy adult lifestyle was associated with elevated risks of CMD progression and mortality. Notably, the detrimental associations of early-life risk factors with specific CMD transitions were less pronounced among individuals with healthier adult lifestyles.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.