患有和未患1型糖尿病的成年人的线粒体DNA拷贝数
Mitochondrial DNA copy number in adults with and without Type 1 diabetes.
作者信息
Jenkins Alicia J, Carroll Luke M, Huang Michael L H, Wen-Loh Yik, Mangani Abubakar, O'Neal David N, Januszewski Andrzej S
机构信息
NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia; Department of Medicine, St. Vincent's Hospital, The University of Melbourne, VIC, Australia; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia.
出版信息
Diabetes Res Clin Pract. 2023 Sep;203:110877. doi: 10.1016/j.diabres.2023.110877. Epub 2023 Aug 12.
AIMS
Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors.
METHODS
Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide.
RESULTS
mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74.
CONCLUSIONS
mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited.
目的
线粒体损伤与糖尿病的发病机制及并发症有关。目前缺乏关于1型糖尿病（T1D）患者线粒体DNA拷贝数（mtDNA-cn）的研究。我们比较了T1D成年患者和非糖尿病成年对照者（CON）的mtDNA-cn与糖尿病并发症及危险因素之间的关系。
方法
横断面研究：178例T1D患者，132例非糖尿病对照者。采用定量聚合酶链反应（qPCR）检测全血mtDNA-cn，并分析其与并发症、炎症及C肽的相关性。
结果
mtDNA-cn（中位数（下四分位数，上四分位数））在以下情况较低：T1D患者与对照者相比（271（189，348）对320（264，410）；p<0.0001）；有肾脏疾病的T1D患者与无肾脏疾病的T1D患者相比（238（180，309）对294（198，364）；p=0.02）；胰岛素注射者与胰岛素泵使用者相比（251（180，340）对322（263，406）；p=0.008）。mtDNA-cn的显著单变量相关因素：T1D患者：（正相关）高密度脂蛋白胆固醇（HDL-C）；（负相关）空腹血糖、白细胞计数（WCC）、可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性细胞间黏附分子-1（sICAM-1）；对照者：（负相关）腰臀比（WHR）。T1D患者中可检测到的C肽随着mtDNA-cn三分位数从低到高而增加（54%，69%，79%，p=0.02）。mtDNA-cn的独立决定因素：T1D患者：（正相关）HDL-C；（负相关）年龄、sICAM-1；曲线下面积（AUROC）为0.71；对照者：（负相关）WCC、从不吸烟，（正相关）女性、脉压；AUROC为0.74。
结论
T1D患者与对照者相比，以及T1D合并肾脏疾病患者的mtDNA-cn较低。在T1D患者中，mtDNA-cn与年龄和炎症呈负相关，与HDL-C、可检测到的C肽及胰岛素泵使用呈正相关。值得进一步开展临床和基础科学研究。
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