Objective: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism.
Methods: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis.
Results: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways.
Conclusion: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.
目的: 探讨糖尿病对冠状动脉慢性完全闭塞（CTO）冠心病患者侧支循环建立影响的调节机制。
方法: 87例经冠脉造影确诊至少1支血管为CTO的冠心病患者，根据Cohen-Rentrop分级标准将侧支循环建立水平分为2组，0~1级为侧支循环水平低患者42例，2~3级为侧支循环水平高患者45例，根据是否合并糖尿病分别比较胰岛素抵抗（IR）水平。应用数学模型稳态模式评估法计算IR指数（HOMA-IR）。22例患者介入术中获得侧支循环及外周血标本，采用非靶向代谢组学比较侧支循环与外周血代谢物差异。
结果: 两组在NT-proBNP（P<0.05）和LVEF（P<0.01）方面比较差异有统计学意义。在非糖尿病CTO患者中，侧支循环水平0~1级组胰岛素抵抗水平高于2~3级组（P<0.01）。CTO伴糖尿病与CTO非糖尿病患者相比，侧支循环及外周血中存在明显差异性代谢物，在侧支循环中，上调代谢物63种，下调48种；外周血中，上调代谢物23种，下调14种。侧支循环中差异性代谢物显著相关的富集通路为芳香化合物降解，脂肪酸生物合成，类固醇降解通路；在外周血中差异代谢物富集通路为戊糖磷酸代谢，细菌趋化性，己内酰胺降解，甘油磷脂代谢，赖氨酸降解通路。
结论: CTO非糖尿病患者中侧支循环建立水平较低者存在明显的胰岛素抵抗。芳香化合物的降解，脂肪酸生物合成，类固醇降解通路与侧支循环形成密切相关。
Keywords: chronic total occlusion; collateral circulation; coronary heart disease; insulin resistance; metabolomics.