Januszewski Andrzej S, Sutanto Surya S, McLennan Susan, O'Neal David N, Keech Anthony C, Twigg Stephen M, Jenkins Alicia J
NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia; University of Melbourne, Department of Medicine, St Vincent's Hospital, Fitzroy, Melbourne, VIC, Australia.
Greg Brown Diabetes and Endocrine Laboratory, Sydney Medical School, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia.
Diabetes Res Clin Pract. 2016 Jul;117:4-11. doi: 10.1016/j.diabres.2016.04.040. Epub 2016 Apr 27.
To determine if white blood cell (WBC) telomeres are shorter in Type 1 diabetes (T1D) than in subjects without diabetes (non-DB), and shorter in T1D subjects with vs. without vascular complications; and to determine associations with vascular biomarkers.
WBC relative telomere length (RTL) was determined by quantitative PCR in a cross-sectional study of 140 non-DB and 199 T1D adults, including 128 subjects without vascular complications (T1DNoCx) and 71 subjects with vascular complications (T1DCx). Relationships of RTL with age, T1D duration, arterial elasticity, pulse pressure and vascular risk factors were determined.
RTL did not differ by gender within T1D and non-DB groups. Age-adjusted RTL was shorter in T1D vs. non-DB subjects (1.48±0.03 AU vs. 1.64±0.04 AU, p=0.002), but did not differ by T1D complication status (T1DNoCX 1.50±0.04 vs. T1DCX 1.46±0.05, p=0.50), nor correlate with arterial elasticity. Univariate analysis in T1D showed RTL correlated (inversely) with age r=-0.27, p=0.0001, T1D duration r=-0.16, p=0.03, and pulse pressure (r=-0.15, p=0.04), but not with HbA1c, BP, renal function (serum creatinine, ACR, eGFR), lipids, insulin sensitivity, inflammation (CRP, CAMs) or oxidative stress (OxLDL, OxLDL/LDL-C, MPO, PON-1). Multiple regression analysis showed independent determinants of RTL were age and T1D presence (r=0.29, p<0.0001).
In this cross-sectional study telomeres were shorter in T1D. RTL correlated inversely with T1D duration, but did not differ by complication status and weakly correlated with pulse pressure and vascular risk factors. Only age and T1D were independent determinants of RTL. Longitudinal studies are merited.
确定1型糖尿病(T1D)患者白细胞(WBC)端粒是否比无糖尿病(非糖尿病,non-DB)受试者的端粒短,以及有血管并发症与无血管并发症的T1D患者相比,前者的端粒是否更短;并确定其与血管生物标志物的关联。
在一项横断面研究中,对140名非糖尿病成年人和199名T1D成年人进行了定量PCR检测,以确定白细胞相对端粒长度(RTL),其中包括128名无血管并发症的受试者(T1D无并发症组,T1DNoCx)和71名有血管并发症的受试者(T1D有并发症组,T1DCx)。确定了RTL与年龄、T1D病程、动脉弹性、脉压和血管危险因素之间的关系。
T1D组和非糖尿病组内的RTL在性别上无差异。年龄校正后的RTL在T1D患者中比非糖尿病受试者短(1.48±0.03任意单位对1.64±0.04任意单位,p=0.002),但在有或无T1D并发症的患者中无差异(T1D无并发症组1.50±0.04对T1D有并发症组1.46±0.05,p=0.50),且与动脉弹性无关。T1D患者的单因素分析显示,RTL与年龄呈负相关(r=-0.27,p=0.0001)、与T1D病程呈负相关(r=-0.16,p=0.03)以及与脉压呈负相关(r=-0.15,p=0.04),但与糖化血红蛋白、血压、肾功能(血清肌酐、尿白蛋白肌酐比值、估算肾小球滤过率)、血脂、胰岛素敏感性、炎症(C反应蛋白、细胞黏附分子)或氧化应激(氧化型低密度脂蛋白、氧化型低密度脂蛋白/低密度脂蛋白胆固醇比值、髓过氧化物酶、对氧磷酶-1)无关。多元回归分析显示,RTL的独立决定因素是年龄和是否患有T1D(r=0.29,p<0.0001)。
在这项横断面研究中,T1D患者的端粒较短。RTL与T1D病程呈负相关,但在有无并发症的患者中无差异,且与脉压和血管危险因素的相关性较弱。只有年龄和是否患有T1D是RTL的独立决定因素。值得进行纵向研究。