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
Abstract Background 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 mor...
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BMC
2025-07-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02832-3 |
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| author | Chieh-Hsin Yang Michael L H Huang Wendy A Davis Alicia J Jenkins Timothy M E Davis |
| author_facet | Chieh-Hsin Yang Michael L H Huang Wendy A Davis Alicia J Jenkins Timothy M E Davis |
| author_sort | Chieh-Hsin Yang |
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| description | Abstract Background 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). Methods 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. Results 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. Conclusions 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. |
| format | Article |
| id | doaj-art-3c59440109ec4d10b4fd41322ec7992e |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-3c59440109ec4d10b4fd41322ec7992e2025-08-20T03:37:19ZengBMCCardiovascular Diabetology1475-28402025-07-0124111310.1186/s12933-025-02832-3Determinants of temporal change in telomere length and its associations with chronic complications and mortality in type 2 diabetes: the Fremantle diabetes study phase IIChieh-Hsin Yang0Michael L H Huang1Wendy A Davis2Alicia J Jenkins3Timothy M E Davis4Baker Heart and Diabetes InstituteBaker Heart and Diabetes InstituteMedical School, University of Western Australia, Fremantle HospitalBaker Heart and Diabetes InstituteMedical School, University of Western Australia, Fremantle HospitalAbstract Background 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). Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12933-025-02832-3Telomere lengthCardiovascular diseaseDiabetes complicationsType 2 diabetesMortality |
| spellingShingle | Chieh-Hsin Yang Michael L H Huang Wendy A Davis Alicia J Jenkins Timothy M E Davis 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 Cardiovascular Diabetology Telomere length Cardiovascular disease Diabetes complications Type 2 diabetes Mortality |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Telomere length Cardiovascular disease Diabetes complications Type 2 diabetes Mortality |
| url | https://doi.org/10.1186/s12933-025-02832-3 |
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