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PhenoAgeAccel is associated with all-cause and cardiovascular mortality in patients with diabetes and prediabetes: A cohort study

Junyu Xi, Zeyu Zhang, Baoluo Hou, Yuqi Wu, Yifei Zhang, Wei Jing Liu

2025Diabetes Research and Clinical Practice9 citationsDOIOpen Access PDF

Abstract

AIMS: Phenotypic Age Acceleration (PhenoAgeAccel) is a measure of biological aging, with higher scores indicating faster aging. Few studies have explored its association with mortality in patients with diabetes or prediabetes. This study aimed to investigate the predictive value of PhenoAgeAccel for all-cause and cardiovascular mortality in these patients. METHODS: NHANES data (1999-2018) from 15,939 participants were analyzed. Phenotypic age was calculated from biomarkers such as albumin, creatinine, and glucose, and PhenoAgeAccel was defined as the residual from regressing phenotypic age on actual age. Mortality associations were assessed via Kaplan-Meier, Cox models, restricted cubic spline (RCS), and subgroup analyses. RESULTS: Per 1-year increase in PhenoAgeAccel was associated with a 5.1 % higher risk of all-cause mortality (HR = 1.051, 95 % CI: 1.046-1.057) and a 5.4 % increased risk of cardiovascular mortality (HR = 1.054, 95 % CI: 1.044-1.065) in patients with diabetes or prediabetes. Highest-quartile (Q4) patients had 191.9 % higher all-cause mortality and 192.6 % higher cardiovascular mortality versus Q1 (both p < 0.001). RCS analysis revealed linear positive associations of PhenoAgeAccel with both all-cause and cardiovascular mortality (both P-nonlinear > 0.05). CONCLUSION: Higher PhenoAgeAccel is associated with increased all-cause and cardiovascular mortality in patients with diabetes and prediabetes.

Topics & Concepts

MedicinePrediabetesDiabetes mellitusCohortInternal medicineCohort studyType 2 diabetesEndocrinologyGenetics, Aging, and Longevity in Model OrganismsEpigenetics and DNA MethylationFrailty in Older Adults
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