PDF(Pubmed)
Abstract：
BACKGROUND: The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets.
METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders.
RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension.
CONCLUSIONS: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.
METHODS: We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders.
RESULTS: Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension.
CONCLUSIONS: Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.
摘要：
背景：糖尿病（DM），血糖性状，血管和瓣膜钙化是复杂和多因素的。探索潜在的介质可以阐明潜在的途径并确定新的治疗靶标。
方法：我们利用单变量和多变量孟德尔随机化（MR）分析来研究关联和中介效应。此外,多变量MR分析纳入了心脏代谢危险因素，允许我们解释潜在的混杂因素。
结果：2型糖尿病（T2DM）和糖化血红蛋白（HbA1c）与冠状动脉钙化（CAC）和钙化性主动脉瓣狭窄（CAVS）均呈正相关。然而,空腹血糖（FG）仅与CAVS相关，与CAC无关。此外,CAVS对FG表现出因果效应。钙水平部分介导T2DM对两种类型钙化的影响。具体来说,血清钙与CAC和CAVS均呈正相关。钙水平对T2DM对CAC和CAVS影响的中介效应分别为6.063%和3.939%,分别。T2DM和HbA1c与钙化之间的关联受体重指数（BMI）和吸烟状况的影响。然而,在调整高血压后,这些关联通常减少.
结论：我们的研究结果表明，DM之间存在遗传支持的因果关系，血糖性状，血管和瓣膜钙化，血清钙起着关键的中介作用。
方法：我们利用单变量和多变量孟德尔随机化（MR）分析来研究关联和中介效应。此外,多变量MR分析纳入了心脏代谢危险因素，允许我们解释潜在的混杂因素。
结果：2型糖尿病（T2DM）和糖化血红蛋白（HbA1c）与冠状动脉钙化（CAC）和钙化性主动脉瓣狭窄（CAVS）均呈正相关。然而,空腹血糖（FG）仅与CAVS相关，与CAC无关。此外,CAVS对FG表现出因果效应。钙水平部分介导T2DM对两种类型钙化的影响。具体来说,血清钙与CAC和CAVS均呈正相关。钙水平对T2DM对CAC和CAVS影响的中介效应分别为6.063%和3.939%,分别。T2DM和HbA1c与钙化之间的关联受体重指数（BMI）和吸烟状况的影响。然而,在调整高血压后,这些关联通常减少.
结论：我们的研究结果表明，DM之间存在遗传支持的因果关系，血糖性状，血管和瓣膜钙化，血清钙起着关键的中介作用。
