Determinants of temporal change in telomere length and its associations with chronic complications and mortality in type 2 diabetes: the Fremantle diabetes study phase II

• Published in: Cardiovascular diabetology Vol. 24; no. 1; pp. 267 - 13
• Main Authors: Yang, Chieh-Hsin, Huang, Michael L H, Davis, Wendy A, Jenkins, Alicia J, Davis, Timothy M E
• Format: Journal Article
• Language: English
• Published: England BioMed Central 03.07.2025; BMC
• Subjects: Adult; Age Factors; Aged; Aging; Australia - epidemiology; Bilirubin; Biomarkers; Cardiovascular disease; Cerebrovascular disease; Chronic Disease; Creatinine; Diabetes; Diabetes complications; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - mortality; Female; Genetic testing; Glucose; Heart attacks; Humans; Ischemia; Longitudinal studies; Male; Middle Aged; Mortality; Prognosis; Prospective Studies; Regression analysis; Research ethics; Risk Assessment; Risk Factors; Statistical analysis; Telomerase; Telomere - genetics; Telomere Homeostasis; Telomere length; Telomere Shortening; Telomeres; Time Factors; Type 2 diabetes; Yeast; Australia; Germany; Type 2 diabetes; Cardiovascular disease; Telomere length; Diabetes complications; Mortality
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-025-02832-3

Relative telomere length (rTL), a biomarker of biological ageing, has been implicated in type 2 diabetes and its complications. We aimed to identify the associates of rTL change over 4 years (∆rTL), and to investigate whether rTL and ∆rTL are associated with complications and mortality in adults with type 2 diabetes from the Australian observational community-based Fremantle Diabetes Study Phase II (FDS2). Participants (n = 819) from the FDS2 cohort had baseline and Year-4 (mean ± SD 4.2 ± 0.4 years) rTL measured by qPCR (intra- and inter-assay %CV: 0.56% and 2.69%, respectively). The rTL change (∆rTL; % change/year) was categorised as Shortened (< - 2.69%), Unchanged (- 2.69% to + 2.69%) or Lengthened (> + 2.69%). Multiple logistic regression identified clinical and biochemical determinants of ∆rTL Shortened versus Not Shortened (Unchanged plus Lengthened). rTL and ∆rTL (continuous and categorical) were added to Cox and competing risk regression models of conventional predictors of major complications, CVD death and all-cause mortality during a mean ± SD 11.5 ± 2.1 years of follow-up. rTL was inversely correlated with age (r = - 0.186, P < 0.001). ∆rTL was shortened in 25.5% subjects, unchanged in 10.5%, and lengthened in 64.0%. Shortening was associated with older age, male sex, smoking, obesity, lipid-modifying drug use, and higher platelet count and serum bilirubin levels (P < 0.05). There were no statistically significant unadjusted or age- and sex-adjusted associations between baseline rTL, Year-4 rTL, or ∆rTL, and any incident micro- or macrovascular complications. In unadjusted Cox regression, ∆rTL lengthening was associated with a lower risk of CVD death (hazard ratio 0.98 (0.97, 0.99), P = 0.042) but this association became non-significant after adjustment for conventional risk factors. In adults with type 2 diabetes, rTL does not always shorten over time. rTL and ∆rTL were associated with baseline conventional cardiometabolic risk factors but not independently with major incident complications. There was a weak association between ∆rTL and CVD mortality. These findings question the utility of rTL and ∆rTL in usual type 2 diabetes care.