Abstract：
Accumulating evidence indicates that plasma metal levels may be associated with Type 2 diabetes mellitus (T2DM) incident risk. Mitochondrial function such as mitochondrial DNA copy number (mtDNA-CN) might be linked to metal exposure and physiological metabolism. Mediation analysis was conducted to determine the mediating roles of mtDNA-CN in the association between plasma metals and diabetes risk. In the present study, we investigated associations between plasma metals levels, mtDNA-CN, and T2DM incident in the elderly population with a 6-year follow-up (two times) study. Ten plasma metals [i.e. manganese, aluminum, calcium, iron, barium (Ba), arsenic, copper, selenium, titanium, and strontium] were measured using inductively coupled plasma mass spectrometry. mtDNA-CN was measured by real-time polymerase chain reaction. Multivariable linear regression and logistic regression analyses were carried out to estimate the relationship between plasma metal concentrations, mtDNA-CN, and T2DM incident risk in the current work. Plasma Ba deficiency and mtDNA-CN decline were associated with T2DM incident risk during the aging process. Meanwhile, plasma Ba was found to be positively associated with mtDNA-CN. Mitochondrial function mtDNA-CN demonstrated mediating effects in the association between plasma Ba deficiency and T2DM incident risk, and 49.8% of the association was mediated by mtDNA-CN. These findings extend the knowledge of T2DM incident risk factors and highlight the point that mtDNA-CN may be linked to plasma metal elements and T2DM incident risk.
摘要：
越来越多的证据表明，血浆金属水平可能与2型糖尿病（T2DM）事件风险有关。线粒体功能，例如线粒体DNA拷贝数（mtDNA-CN）可能与金属暴露和生理代谢有关。进行中介分析以确定mtDNA-CN在血浆金属与糖尿病风险关联中的中介作用。在本研究中,我们调查了血浆金属水平之间的关联，对老年人群mtDNA-CN和T2DM事件进行6年(2次)随访研究。十种等离子体金属(即锰(Mg)，铝(Al),钙(Ca),铁(Fe),钡(Ba),砷（As），铜(Cu),硒(Se),通过使用电感耦合等离子体质谱法(ICP-MS)测量钛(Ti)和铯(Sr)。通过实时PCR测量线粒体DNA拷贝数。进行了多变量线性回归和逻辑回归模型来估计血浆金属浓度之间的关系，mtDNA-CN和T2DM事件风险当前工作。衰老过程中血浆Ba缺乏和mtDNA-CN下降与T2DM发病风险相关.同时发现血浆Ba与mtDNA-CN呈正相关。线粒体功能mtDNA-CN在血浆Ba缺乏与T2DM发病风险之间具有中介作用,49.8%的关联是由mtDNA-CN介导的。这些发现扩展了对T2DM事件危险因素的认识，并强调了mtDNA-CN可能与金属元素和T2DM事件风险相关的观点。
