| Title: | Life-course body size trajectories and the progression of cardio-renal-metabolic multimorbidity: a prospective UK biobank study |
| Journal: | Nutrition & Metabolism |
| Published: | 4 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42243983/ |
| DOI: | https://doi.org/10.1186/s12986-026-01148-7 |
Publication 19778
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Abstract
BackgroundThe influence of life-course body size on the progression of cardio-renal-metabolic multimorbidity (CRMM) is insufficiently understood.MethodsWe included 398,491 UK Biobank participants. Childhood-to-adulthood body size trajectories were defined using recalled childhood somatotype and adult body mass index (BMI). Multi-state models evaluated transition-specific hazards, state-occupation probabilities, and expected length of stay (ELOS) across body size trajectories. Progression was represented as a comorbidity-count pathway (healthy, first/double/triple CRMM, and death) and a comorbidity-pattern pathway specifying the entry disease and comorbidities among cardiovascular disease (CVD), type 2 diabetes (T2D), and chronic kidney disease (CKD). Subgroup and interaction analyses evaluated joint effects of trajectory and Life's Essential 4 (LE4). Mediation by the C-reactive protein-triglyceride-glucose index (CTI) was assessed.ResultsTrajectories culminating in obesity were associated with higher hazards along the comorbidity-count pathway and shorter healthy time (ELOS 13.08 vs. 10.59 years for Average-to-normal vs Thinner-to-obesity). Comorbidity-pattern analyses identified T2D-containing comorbidities (T2D-CKD, T2D-CVD) as hubs toward CRMM. Compared with the Average-to-normal group, hazard ratios (HRs) were highest when the destination included T2D: CVD to T2D-CVD, 3.24 (Plumper-to-obesity), and 3.85 (Thinner-to-obesity); CKD to T2D-CKD, 2.66 (Plumper-to-obesity) and 4.03 (Thinner-to-obesity). Moving from LE4-low to LE4-high attenuated the risks of CRMM associated with progressive or persistent obesity trajectories by 26.8-37.8%. CTI mediated approximately 42-54% of the associations between sustained or progressive obesity trajectories and CRMM comorbidity outcomes.ConclusionsProgressive or persistent obesity trajectories were associated with higher CRMM progression hazards. Early adiposity prevention and sustained lifestyle improvement may slow this progression. Integrating body size trajectory and lifestyle factors with metabolic inflammation indicators may strengthen risk stratification.</p>
8 Authors
- Jingjing Lang
- Zhongyang Guan
- Lili Li
- Lu Jiang
- Guanghui Mao
- Guochong Chen
- Mario Siervo
- Xiaoyan Shi
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