Shortened Relative Leukocyte Telomere Length is Associated with All-cause Mortality in Type 2 Diabetes- Analysis from the Hong Kong Diabetes Register

2021 ◽  
pp. 108649
Author(s):  
Feifei Cheng ◽  
Andrea O Luk ◽  
Hongjiang Wu ◽  
Cadmon KP Lim ◽  
Luke Carroll ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hong Kong ◽  
Telomere Length ◽  
Leukocyte Telomere Length ◽  
All Cause Mortality ◽  
Diabetes Register

scholarly journals Shortened Relative Leukocyte Telomere Length is Associated with Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes- Analysis from the Hong Kong Diabetes Register

2020 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O Luk ◽  
Claudia HT Tam ◽  
Baoqi Fan ◽  
Hongjiang Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hong Kong ◽  
Telomere Length ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Hazard Ratio ◽  
Chinese Patients ◽  
Diabetes Register

<b>Objective</b>: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes. <p><b>Research design and methods</b>: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code.</p> <p><b>Results: </b>Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA<sub>1c</sub>, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA<sub>1c</sub>, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001).</p> <p><b>Conclusions: </b>rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.</p> <b><br> </b>

scholarly journals Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register

Diabetologia ◽  
2021 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O. Luk ◽  
Hongjiang Wu ◽  
Claudia H. T. Tam ◽  
Cadmon K. P. Lim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hong Kong ◽  
Kidney Disease ◽  
Telomere Length ◽  
Rapid Decline ◽  
End Stage Kidney Disease ◽  
End Stage ◽  
Diabetes Register

Abstract Aims/hypothesis Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract

scholarly journals Shortened Relative Leukocyte Telomere Length is Associated with Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes- Analysis from the Hong Kong Diabetes Register

2020 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O Luk ◽  
Claudia HT Tam ◽  
Baoqi Fan ◽  
Hongjiang Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hong Kong ◽  
Telomere Length ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Hazard Ratio ◽  
Chinese Patients ◽  
Diabetes Register

<b>Objective</b>: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes. <p><b>Research design and methods</b>: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code.</p> <p><b>Results: </b>Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA<sub>1c</sub>, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA<sub>1c</sub>, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001).</p> <p><b>Conclusions: </b>rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.</p> <b><br> </b>

scholarly journals Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: A Mendelian randomization study

2021 ◽  
Author(s):  
Resham L Gurung ◽  
Rajkumar Dorajoo ◽  
Yiamunaa M ◽  
Ling Wang ◽  
Sylvia Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Telomere Length ◽  
Mendelian Randomization ◽  
Random Effect ◽  
Leukocyte Telomere Length ◽  
Increased Risk ◽  
Genetically Determined

Abstract Background Chronic kidney disease (CKD) is common among type 2 diabetes (T2D) and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length is associated with CKD in patients with T2D. We previously reported single nucleotide polymorphisms (SNPs) associated with leukocyte telomere length in Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using Mendelian randomization (MR) approach. Methods The cross-sectional association of 16 leukocyte telomere length SNPs with CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min/1.73m2 was assessed among 4,768 (1,628 cases, 3,140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analysed. Results Genetically determined shorter leukocyte telomere length was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio = 1.51 [95% confidence interval, 1.12 - 2.12; P = 0.007; Phet= 0.547]). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (β  =  0.010, P = 0.751). Conclusions Our findings suggest that genetically determined leukocyte telomere length is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.

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