Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia.
Clinical Investigation Centre, University Malaya Medical Centre, 59100, Lembah Pantai, Kuala Lumpur, Malaysia.
Clin Exp Med. 2018 Aug;18(3):373-382. doi: 10.1007/s10238-018-0495-4. Epub 2018 Mar 17.
Altered mitochondrial DNA (mtDNA) is the most common denominator to numerous metabolic diseases. The present study sought to investigate the correlation between mtDNA content in lymphocytes and associated clinical risk factors for impaired fasting glucose (IFG). We included 23 healthy control and 42 IFG participants in this cross-sectional study. The measurements of mtDNA content in lymphocytes and pro-inflammatory markers derived from both normal and diseased individuals were quantified. Spearman partial correlation and multivariate statistical analyses were employed to evaluate the association between mtDNA content and other metabolic covariates in IFG. Reduced mtDNA content was observed in the IFG group with microvascular complications than those without complications. The IFG patients with lowest median of mtDNA content had considerably elevated hyperglycemia, insulin resistance and inflammation. The adjusted partial correlation analysis showed that mtDNA content was positively correlated with HDL-cholesterol and IL-10 (P < 0.005 for all). Further, multiple linear regression analyses verified that reduced mtDNA content in lymphocytes was independently associated with HOMA-IR (β = 0.027, P = 0.003), HbA1c (β = 0.652, P = 0.002), HDL-cholesterol (β = - 1.056, P = 0.021), IL-6 (β = 0.423, P = 0.002), IL-10 (β = - 1.234, P = 0.043) and TNF-α (β = 0.542, P < 0.001) after adjustment for confounding factors. Our data show that reduced mtDNA content in lymphocytes was associated with insulin resistance and inflammation in individuals with IFG.
线粒体 DNA(mtDNA)改变是许多代谢性疾病的共同特征。本研究旨在探讨淋巴细胞 mtDNA 含量与空腹血糖受损(IFG)相关临床危险因素之间的相关性。我们纳入了 23 名健康对照者和 42 名 IFG 参与者进行这项横断面研究。定量检测了淋巴细胞中 mtDNA 含量和来自正常和患病个体的促炎标志物。采用 Spearman 偏相关和多变量统计分析评估了 IFG 中 mtDNA 含量与其他代谢协变量之间的关系。与无微血管并发症的 IFG 组相比,IFG 组中观察到 mtDNA 含量减少。mtDNA 含量最低的 IFG 患者的高血糖、胰岛素抵抗和炎症明显升高。调整后的偏相关分析显示,mtDNA 含量与 HDL-胆固醇和 IL-10 呈正相关(所有 P<0.005)。此外,多元线性回归分析验证了淋巴细胞中 mtDNA 含量减少与 HOMA-IR(β=0.027,P=0.003)、HbA1c(β=0.652,P=0.002)、HDL-胆固醇(β=-1.056,P=0.021)、IL-6(β=0.423,P=0.002)、IL-10(β=-1.234,P=0.043)和 TNF-α(β=0.542,P<0.001)独立相关,调整混杂因素后。我们的数据表明,IFG 个体中淋巴细胞 mtDNA 含量减少与胰岛素抵抗和炎症有关。