Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes
Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes
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DOI：
10.1007/s11010-012-1276-0
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发表时间：
2012-06-01
影响因子：
4.3
通讯作者：
Balasubramanyam, Muthuswamy
中科院分区：
文献类型：
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作者：
Monickaraj, Finny;Aravind, Sankaramoorthy;Balasubramanyam, Muthuswamy
虽然端粒缩短与糖尿病的几个危险因素有关，但缺乏关于其与线粒体功能障碍关系的数据。因此，我们比较了2型糖尿病患者（T2 DM; n = 145）和正常糖耐量（NGT; n = 145）受试者端粒长度和线粒体DNA（mtDNA）含量之间的关系。受试者是从钦奈城乡流行病学研究中随机招募的。用Real-Time PCR检测线粒体DNA含量和端粒长度。丙二醛，脂质过氧化反应的标志物，硫代巴比妥酸反应物质（TBARS）使用荧光法测定。采用放射免疫法测定脂联素水平。与NGT受试者相比，T2 DM患者中通过脂质过氧化（TBARS）测定的氧化应激显著（p < 0.001）更高。相反，T2 DM患者的平均端粒长度、脂联素和mtDNA含量显著低于NGT受试者（p < 0.001）。端粒长度与脂联素、高密度脂蛋白、线粒体DNA含量和良好的血糖/血脂控制呈正相关，与肥胖和胰岛素抵抗呈负相关。在回归分析中，缩短的端粒显示与T2 DM显著相关，即使在调整腰围、胰岛素抵抗、甘油三酯、HDL、脂联素、mtDNA和TBARS之后。在调整腰围和脂联素后，mtDNA缺失与T2 DM显著相关，但进一步调整端粒长度、TBARS和胰岛素抵抗后，mtDNA缺失失去了意义。我们的研究强调了加速老化特征的聚集，亚洲印度2型糖尿病患者中端粒缩短、mtDNA含量降低、低脂联素血症、低HDL和氧化应激增加。
Although shortened telomeres were shown associated with several risk factors of diabetes, there is lack of data on their relationship with mitochondrial dysfunction. Therefore, we compared the relationship between telomere length and mitochondrial DNA (mtDNA) content in patients with type 2 diabetes mellitus (T2DM; n = 145) and in subjects with normal glucose tolerance (NGT; n = 145). Subjects were randomly recruited from the Chennai Urban Rural Epidemiology Study. mtDNA content and telomere length were assessed by Real-Time PCR. Malonodialdehyde, a marker of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) using fluorescence methodology. Adiponectin levels were measured by radioimmunoassay. Oxidative stress as determined by lipid peroxidation (TBARS) was significantly (p < 0.001) higher in patients with T2DM compared to NGT subjects. In contrast, the mean telomere length, adiponectin and mtDNA content were significantly (p < 0.001) lower in patients with T2DM compared to NGT subjects. Telomere length was positively correlated with adiponectin, HDL, mtDNA content and good glycemic/lipid control and negatively correlated with adiposity and insulin resistance. On regression analysis, shortened telomeres showed significant association with T2DM even after adjusting for waist circumference, insulin resistance, triglyceride, HDL, adiponectin, mtDNA & TBARS. mtDNA depletion showed significant association with T2DM after adjusting for waist circumference and adiponectin but lost its significance when further adjusted for telomere length, TBARS and insulin resistance. Our study emphasizes the clustering of accelerated aging features viz., shortened telomeres, decreased mtDNA content, hypoadiponectinemia, low HDL, and increased oxidative stress in Asian Indian type 2 diabetes patients.