| Title: | Association of accelerated phenotypic aging, genetic risk, and lifestyle with progression of type 2 diabetes: a prospective study using multi-state model |
| Journal: | BMC Medicine |
| Published: | 4 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39901253/ |
| DOI: | https://doi.org/10.1186/s12916-024-03832-y |
| URL: | https://link.springer.com/content/pdf/10.1186/s12916-024-03832-y.pdf |
Publication 15174
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BackgroundAging is a major risk factor for type 2 diabetes (T2D), but individuals of the same chronological age may vary in their biological aging rate. The associations of Phenotypic Age Acceleration (PhenoAgeAccel), a new accelerated biological aging indicator based on clinical chemistry biomarkers, with the risk of dynamic progression remain unclear. We aimed to assess these associations and examine whether these associations varied by genetic risk and lifestyle.MethodsWe conducted a prospective cohort study that included 376,083 adults free of T2D and diabetes-related events at baseline in UK Biobank. PhenoAgeAccel > 0 and ≤ 0 were defined as biologically older and younger than chronological age. The outcomes of interest were incident T2D, diabetic complications, and mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) and population attributable fractions (PAFs) for these associations were calculated using multi-state model.ResultsDuring a median follow-up of 13.7 years, 17,615 participants developed T2D, of whom, 4,524 subsequently developed complications, and 28,373 died. Being biologically older was associated with increased risks of transitions from baseline to T2D (HR 1.77, 95% CI 1.71-1.82; PAF 24.8 [95% CI 23.5-26.2]), from T2D to diabetic complications (1.10, 1.04-1.17; 4.4 [1.4-7.4]), from baseline to all-cause death (1.53, 1.49-1.57; 17.6 [16.6-18.6]), from T2D to all-cause death (1.14, 1.03-1.26; 7.4 [1.8-13.0]), and from diabetic complications to all-cause death (1.32, 1.15-1.51; 15.4 [7.5-23.2]) than being biologically younger. Additionally, participants with older biological age and high genetic risk had a higher risk of incident T2D (4.76,4.43-5.12;18.2 [17.5-19.0]) than those with younger biological age and low genetic risk. Compared with participants with younger biological age and healthy lifestyle, those with older biological age and unhealthy lifestyle had higher risks of transitions in the T2D trajectory, with HRs and PAFs ranging from 1.34 (1.16-1.55; 3.7 [1.8-5.6]) to 5.39 (5.01-5.79; 13.0 [12.4-13.6]).ConclusionsPhenoAgeAccel was consistently associated with an increased risk of all transitions in T2D progression. It has the potential to be combined with genetic risk to identify early T2D incidence risk and may guide interventions throughout T2D progression while tracking their effectiveness.</p>
15 Keywords
- Adult
- Aged
- Aging
- Diabetes Mellitus, Type 2
- Disease Progression
- Female
- Genetic Predisposition to Disease
- Humans
- Life Style
- Male
- Middle Aged
- Phenotype
- Prospective Studies
- Risk Factors
- United Kingdom
9 Authors
- Lulu Pan
- Yahang Liu
- Chen Huang
- Yifang Huang
- Ruilang Lin
- Kecheng Wei
- Ye Yao
- Guoyou Qin
- Yongfu Yu
1 Application
| Application ID | Title |
|---|---|
| 96511 | Investigating the genome-wide association and risk factors for multi-organ ageing |
Enabling scientific discoveries that improve human health