Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, China.
Diabet Med. 2012 Jul;29(7):e47-54. doi: 10.1111/j.1464-5491.2011.03565.x.
Mitochondrial DNA (mtDNA) content is essential for maintaining normal mitochondrial function, and the mitochondrial function is critical for the production and the release of insulin in Type 2 diabetes mellitus. We investigated whether peripheral blood mtDNA content was reduced in Type 2 diabetes, and what were the major factors?
The mtDNA content of peripheral blood in a sample of 147 Type 2 diabetes and 170 normal Chinese subjects was determined by amplification of the mitochondrial gene CYT-B and normalized by a nuclear DNA β-globin gene. Fasting plasma glucose, HbA(1c) , fasting plasma insulin and lipid profile (HDL-cholesterol, LDL-cholesterol, total cholesterol, triglyceride) were analysed with commercial kits on an automatic analyser.
In Type 2 diabetes group, the mean HbA(1c) was 62 mmol/mol (7.8%). Moreover, BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, LDL-cholesterol, triglyceride, fasting plasma insulin and homeostasis model assessment for insulin resistance were significantly higher in Type 2 diabetes group than that in control group. Peripheral blood mtDNA content was 24% lower than that in the controls (1.4 ± 0.5 vs. 1.8 ± 0.7, P < 0.001). The mtDNA content was negatively correlated with BMI, fasting plasma glucose, fasting plasma insulin, homeostasis model assessment for insulin resistance (P < 0.01), and age, triglyceride and LDL-cholesterol levels (P < 0.05); while positively correlated with HDL-cholesterol level (P < 0.05) in both groups. Stepwise regression analysis indicated that HbA(1c), fasting plasma glucose and age of onset were the major factors affecting the mtDNA content in the Type 2 diabetes group; however, BMI was the only variable associated with lower mtDNA content in control group.
Our results demonstrate that lower peripheral blood mtDNA content is associated with Type 2 diabetes in Chinese individuals, and HbA(1c), fasting plasma glucose and age of onset are the major factors affecting the mtDNA content.
线粒体 DNA(mtDNA)含量对于维持正常的线粒体功能至关重要,而线粒体功能对于 2 型糖尿病中胰岛素的产生和释放至关重要。我们研究了 2 型糖尿病患者外周血 mtDNA 含量是否降低,以及主要因素是什么?
我们通过扩增线粒体基因 CYT-B 并将其标准化为核 DNA β-球蛋白基因,来确定 147 名 2 型糖尿病患者和 170 名中国正常对照者外周血中的 mtDNA 含量。采用自动分析仪,用商业试剂盒分析空腹血糖、HbA1c、空腹血浆胰岛素和血脂谱(高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、总胆固醇、甘油三酯)。
在 2 型糖尿病组中,HbA1c 的平均值为 62mmol/mol(7.8%)。此外,2 型糖尿病组的 BMI、收缩压、舒张压、空腹血糖、LDL 胆固醇、甘油三酯、空腹血浆胰岛素和胰岛素抵抗的稳态模型评估均高于对照组。外周血 mtDNA 含量比对照组低 24%(1.4±0.5 比 1.8±0.7,P<0.001)。mtDNA 含量与 BMI、空腹血糖、空腹血浆胰岛素、胰岛素抵抗的稳态模型评估呈负相关(P<0.01),与年龄、甘油三酯和 LDL 胆固醇水平呈负相关(P<0.05);而与两组的 HDL 胆固醇水平呈正相关(P<0.05)。逐步回归分析表明,HbA1c、空腹血糖和发病年龄是影响 2 型糖尿病患者 mtDNA 含量的主要因素;然而,BMI 是对照组中与较低 mtDNA 含量相关的唯一变量。
我们的研究结果表明,中国人外周血 mtDNA 含量较低与 2 型糖尿病有关,HbA1c、空腹血糖和发病年龄是影响 mtDNA 含量的主要因素。