Cheng Feifei, Luk Andrea O, Tam Claudia H T, Fan Baoqi, Wu Hongjiang, Yang Aimin, Lau Eric S H, Ng Alex C W, Lim Cadmon K P, Lee Heung Man, Chow Elaine, Kong Alice P, Keech Anthony C, Joglekar Mugdha V, So Wing Yee, Jenkins Alicia J, Chan Juliana C N, Hardikar Anandwardhan A, Ma Ronald C W
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
Diabetes Care. 2020 Sep;43(9):2257-2265. doi: 10.2337/dc20-0028. Epub 2020 Jul 13.
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.
Consecutive Chinese patients with type 2 diabetes ( = 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.
Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA, and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all < 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) ( < 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 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) ( < 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], < 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA, eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084-1.200], < 0.001).
rLTL 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.
多项研究支持生物衰老的生物标志物——相对白细胞端粒长度(rLTL)与2型糖尿病之间存在潜在联系。本研究调查2型糖尿病患者中rLTL与心血管疾病(CVD)发病之间的关系。
对来自香港糖尿病登记处的5349例连续的2型糖尿病中国患者进行研究,这些患者在基线时获取的DNA被保存且有随访数据。通过定量PCR测量rLTL。根据国际疾病分类第九版(ICD-9)编码诊断CVD。
平均随访时间为13.4年(标准差5.5年)。rLTL与年龄、糖尿病病程、血压、糖化血红蛋白(HbA)以及尿白蛋白与肌酐比值(ACR)呈负相关,与估计肾小球滤过率(eGFR)呈正相关(均P<0.001)。基线时患有CVD的受试者的rLTL(4.3±1.2ΔΔCt)比无CVD的受试者(4.6±1.2ΔΔCt)短(P<0.001)。在基线时无CVD的4541名受试者中,随访期间发生CVD的1140名受试者的rLTL(4.3±1.2ΔΔCt)比在调整年龄、性别、吸烟和蛋白尿状态后仍无CVD的受试者(4.7±1.2ΔΔCt)短(P<0.001)。在Cox回归模型中,较短的rLTL与CVD发病风险较高相关(每降低一个单位,风险比为1.252[95%置信区间1.195 - 1.311],P<0.001),在调整年龄、性别、体重指数(BMI)、收缩压、低密度脂蛋白胆固醇、HbA、eGFR和ACR后仍具有显著性(风险比为1.141[95%置信区间1.084 - 1.200],P<0.001)。
2型糖尿病合并CVD患者的rLTL显著缩短,与心脏代谢危险因素相关,且与CVD发病独立相关。端粒长度可能是2型糖尿病患者CVD风险的一个有用生物标志物。