Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes
Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes
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DOI：
10.1111/j.1365-2796.2009.02139.x
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发表时间：
2010-03-01
影响因子：
11.1
通讯作者：
Groop, P. -H.
中科院分区：
文献类型：
--
作者：
Fyhrquist, F.;Tiitu, A.;Groop, P. -H.
目标.确定1型糖尿病患者血液白细胞端粒长度短是否与糖尿病肾病进展相关或预测糖尿病肾病进展。设计和方法。两个连续的DNA样本来自全国范围内的芬兰糖尿病肾病研究的132例1型糖尿病患者。对照DNA样本取自44名健康献血者。Southern印迹法测定端粒长度。根据尿白蛋白排泄率（AER）将患者分为三组：48例正常白蛋白尿（AER < 20 μ g min（-1）），7例微量白蛋白尿（AER >= 20 μ g min（-1）< 200 μ g min（-1））和77例大量白蛋白尿（AER >= 200 μ g min（-1））。进展定义为白蛋白尿水平升高。21例患者发生进展。与非进展者（分别为8.5 +/-0.7 kb和27 +/-7.2%）相比，进展者的平均端粒长度较短（8.1 +/- 0.7 kb，平均值+/- SD; P = 0.017），短端粒百分比较高（32.0 +/-8%，P = 0.002）。因此，较短的端粒（HR = 0.190，95%CI 0.065-0.558，P = 0.0025）和较高比例的短端粒（HR = 1.115，1.039-1.195，P =0.0023）是糖尿病肾病的独立预测因子。端粒长度与蛋白尿的程度无关，在1型糖尿病患者中与健康对照组相比没有差异。短端粒是1型糖尿病患者糖尿病肾病进展的独立预测因子。
Objectives. To determine whether short telomere length of blood leucocytes from patients with type 1 diabetes is associated with or predictive of progression of diabetic nephropathy.Design and methods. Two consecutive DNA samples were obtained from 132 patients from the nationwide Finnish Diabetic Nephropathy Study with type 1 diabetes. Control DNA samples were taken from 44 healthy blood donors. Telomere length was measured by Southern blot. Patients were divided into three groups according to their urinary albumin excretion rate (AER): 48 patients with normoalbuminuria (AER < 20 mu g min(-1)); seven patients with microalbuminuria (AER >= 20 mu g min(-1) < 200 mu g min(-1)) and 77 patients with macroalbuminuria (AER >= 200 mu g min(-1)). Progression was defined as a change in albuminuria to a higher level.Results. Progression occurred in 21 patients. Progressors had shorter mean telomere length (8.1 +/- 0.7 kb, mean +/- SD; P = 0.017) and higher percentage of short telomeres (32.0 +/- 8%, P = 0.002) than nonprogressors (8.5 +/- 0.7 kb and 27 +/- 7.2%, respectively). Thus, both shorter telomeres (HR = 0.190, 95%CI 0.065-0.558, P = 0.0025) and higher proportion of short telomeres (HR = 1.115, 1.039-1.195, P =0.0023) were independent predictors of diabetic nephropathy. Telomere length was not associated with the degree of albuminuria and was not different in patients with type 1 diabetes compared with healthy controls.Conclusions. Short telomeres are independent predictors of progression of diabetic nephropathy in patients with type 1 diabetes.