Shortened Relative Leukocyte Telomere Length Is Associated With Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes: Analysis From the Hong Kong Diabetes Register

Abstract

Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and incident cardiovascular disease (CVD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODSConsecutive Chinese patients with type 2 diabetes (N 5 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code. RESULTSMean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA 1c , and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all P < 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 6 1.2 DDCt) than did subjects without CVD (4.6 6 1.2 DDCt) (P < 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 6 1.2 DDCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 6 1.2 DDCt) (P < 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 [95% CI 1.195-1.311], P < 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA 1c , eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084-1.200], P < 0.001). CONCLUSIONSrLTL is significantly shorter in patients with type 2 diabetes and 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 patients with type 2 diabetes.

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

“…Given that men had more risk factors than women, possibly contributing towards their higher risk of cardiovascular and kidney complications, telomere shortening might take on more important prognostic significance in women. This sex difference was also observed in our previous report on the risk association between rLTL and incident CVD [5].…”

“…Relative LTL measurements DNA was extracted from the whole blood of participants and stored in freezers after extraction [5]. DNA extractions were mainly conducted from 1997 onwards, with most samples extracted within 1 year of blood collection, using a traditional phenol-chloroform method [5].…”

“…Relative LTL measurements DNA was extracted from the whole blood of participants and stored in freezers after extraction [5]. DNA extractions were mainly conducted from 1997 onwards, with most samples extracted within 1 year of blood collection, using a traditional phenol-chloroform method [5]. Telomere length measurements were conducted using an updated quantitative real-time PCR method [5,18,19] and were reported as ΔΔC t between telomere and single-copy gene (encoding human β-globin [HBG]) relative to a normalisation control.…”

“…Telomeres are tandem repeats of 5′-TTAGGG-3′ sequences at the ends of each DNA strand within every chromosome [ 4 ]. Telomere length is a useful biomarker of chronological age and age-related disorders such as CVD [ 5 ], mortality [ 6 ] and cancer [ 7 ]. In a cross-sectional study, 137 patients with ESKD had shorter leucocyte telomere length (LTL) than 144 healthy controls [ 8 , 9 ].…”

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

“…Therefore, telomere length is recognized as a biomarker for cellular aging [ 5 ]. Leukocyte telomere length (LTL), predominantly measured in epidemiological studies, is correlated with telomere length in multiple tissues in humans, including kidney tissues [ 6–8 ], and is inversely associated with risk of aging-related diseases including cardiovascular disease and all-cause mortality [ 9–11 ].…”