1 型糖尿病患者端粒长度与糖尿病肾病进展。

Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes.

机构信息

Minerva Institute for Medical Research, Biomedicum Helsinki, 00290 Helsinki, Finland.

出版信息

J Intern Med. 2010 Mar;267(3):278-86. doi: 10.1111/j.1365-2796.2009.02139.x. Epub 2009 Jun 4.

DOI:10.1111/j.1365-2796.2009.02139.x

PMID:19563389

Abstract

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 microg min(-1)); seven patients with microalbuminuria (AER > or = 20 microg min(-1) <200 microg min(-1)) and 77 patients with macroalbuminuria (AER > or = 200 microg 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.

摘要

目的

确定 1 型糖尿病患者白细胞端粒长度较短是否与糖尿病肾病的进展有关或可预测其进展。

设计和方法

从全国性的芬兰糖尿病肾病研究中连续采集了 132 例 1 型糖尿病患者的 2 个连续 DNA 样本。对照 DNA 样本取自 44 名健康献血者。通过 Southern blot 测定端粒长度。根据尿白蛋白排泄率（AER）将患者分为三组：48 例正常白蛋白尿患者（AER<20μgmin-1）；7 例微量白蛋白尿患者（AER≥20μgmin-1<200μgmin-1）和 77 例大量白蛋白尿患者（AER≥200μgmin-1）。进展定义为蛋白尿水平升高。

结果

21 例患者发生进展。进展者的平均端粒长度较短（8.1±0.7kb，平均值±标准差；P=0.017），短端粒比例较高（32.0±8%，P=0.002），而非进展者分别为 8.5±0.7kb 和 27±7.2%（P=0.002）。因此，端粒较短（HR=0.190，95%CI 0.065-0.558，P=0.0025）和短端粒比例较高（HR=1.115，1.039-1.195，P=0.0023）都是糖尿病肾病的独立预测因素。端粒长度与白蛋白尿程度无关，1 型糖尿病患者的端粒长度与健康对照者也无差异。