上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2017, Vol. 37 ›› Issue (6): 744-.doi: 10.3969/j.issn.1674-8115.2017.06.006

• 论著（基础研究） • 上一篇    下一篇

基线脂代谢谱特征对降糖药物干预再发心血管事件影响的预测研究

赵丹丹 1，顾燕云 1，王计秋 1，胡春秀 2，洪洁 1，张翼飞 1，SPREAD-DIMCAD 研究组 1   

  1. 1. 上海交通大学 医学院附属瑞金医院内分泌代谢病科，上海市内分泌代谢病研究所，上海市内分泌代谢病临床医学中心，上海 200025； 2 . 中国科学院 大连化学物理研究所分离分析化学重点实验室，大连 116023
  • 出版日期:2017-06-28 发布日期:2017-07-05
  • 通讯作者: 张翼飞，电子信箱：feifei-a@163.com
  • 作者简介:?赵丹丹（1991—），女，硕士生；电子信箱：zhxiaoxin@sjtu.edu.cn
  • 基金资助:

     国家自然科学基金项目（81471074，81670797）；上海市科学技术发展基金（14411964700）；上海市教育委员会高峰高原学科建设计划（20161411）； 国家重点研发计划项目（2016YFC0901200）；上海市教育委员会“曙光计划”项目（14SG17）

Study on the predictive effect of baseline lipid profiles on recurrent cardiovascular events after antidiabetic drugs intervention

ZHAO Dan-dan1, GU Yan-yun1, WANG Ji-qiu1, HU Chun-xiu2, HONG Jie1, ZHANG Yi-fei1, the SPREAD-DIMCAD study group1   

  1. 1. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
  • Online:2017-06-28 Published:2017-07-05
  • Supported by:

    National Natural Science Foundation of China, 81471074,81670797; Shanghai Foundation for Development of Science and Technology, 14411964700; Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support, 20161411; National Key R&D Plan, 2016YFC0901200; “Dawn” Program of Shanghai Education Commission, 14SG17

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摘要：

目的 · 探讨基线脂代谢谱与降糖药物格列吡嗪和二甲双胍干预后心血管结局的关系，寻找能够预测格列吡嗪和二甲双胍长期心 血管效应的脂质组分。方法 · 选取 116 例分别接受格列吡嗪（56 例）和二甲双胍（60 例）治疗 3 年的 2 型糖尿病（T2DM）合并冠状动 脉粥样硬化性心脏病（CHD）患者，运用液相色谱 -四级杆飞行时间质谱联用技术（LC-QTOF/MS）测定基线血清中的 119 种脂质组分。 随访所有患者心血管复合终点（包括心血管死亡、全因死亡、非致命性心肌梗死、非致命性脑卒中及冠脉血运重建）的发生情况。通过 Logistic 回归分析脂质组分与患者心血管复合终点的关系。采用连续净重新分类指数（cfNRI）和整体鉴别指数（IDI）评价基线脂质组分 是否有助于提高对再发心血管事件的预测能力。结果 · 除利尿剂使用率和 PC（O-34:2）及 SM（d18:0-24:0）水平外，2 组间基线药物分 布及临床特征和生化指标的差异均无统计学意义。Logistic 回归分析结果显示：基线 ChE（20:4）是格列吡嗪组患者再发心血管事件的保 护性因素（OR=0.87，P=0.039）； ChE（20:4）显著提高了心血管复合终点的cfNRI 和 IDI，分别为69% 和 0.07（P=0.011，P=0.028）。基 线 SM（d18:1-22:0）是二甲双胍组患者和全部受试者再发心血管事件的危险因素（OR=1.65，P=0.039；OR=1.64，P=0.014）； SM（d18:122:0）显著提高了二甲双胍组和全部受试者的心血管复合终点的 cfNRI，分别为 74% 和55%（P=0.012，P=0.005）。 结论 · 在由 LC-QTOF/ MS 方法测得的 119 种脂质组分中，基线 ChE（20:4）和 SM（d18:1-22:0）可分别为 T2DM 合并 CHD 患者接受格列吡嗪和二甲双胍长期 治疗后出现心血管复合终点的保护性和危险因素，且均有助于提高预测再发心血管事件风险的准确性。

关键词: 2 型糖尿病, 心血管疾病, 脂代谢谱, 二甲双胍, 格列吡嗪

Abstract:

 Objective · To explore the relationship between baseline lipid profiles and long-term cardiovascular outcomes after intervention with hypoglycemic drugs metformin and glipizide and to detect lipid components that can predict the long-term cardiovascular effect of metformin and glipizide.  Methods · Liquid chromatography–quadrupole time of flight–mass spectrometry (LC-QTOF/MS) was used to measure 119 lipid components in baseline serum for 116 patients with type 2 diabetes (T2DM) and atherosclerotic heart disease (CHD) who were treated with glipizide (56 cases, the glipizide group) or metformin (60 cases, the metformin group). Cardiovascular complex end points (including cardiovascular death, all-cause death, nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization) of all patients were followed up. The relationship between lipid components and cardiovascular  complex end points was analyzed with Logistic regression analysis. The category-free net reclassification index (cfNRI) and the integrated discrimination improvement (IDI) were used to evaluate whether lipid components are helpful for predicting the recurrent cardiovascular events.  Results · The differences in baseline drug distribution, clinical characteristics, and biochemical indexes between two groups were not statistically significant, except for diuretics use, serum PC (O-34:2) level, and SM (d18:0-24:0) level. Logistic regression analysis showed that baseline ChE (20:4) was a protective factor for recurrent cardiovascular events in the glipizide group (OR=0.87, P=0.039). ChE (20:4) significantly increased the cfNRI and IDI of cardiovascular  complex end points by 69% and 0.07, respectively (P=0.011, P=0.028). Baseline SM (d18:1-22:0) was a risk factor for recurrent cardiovascular events in the metformin group and all participants (OR=1.65, P=0.039; OR=1.64, P=0.014). SM (d18:1-22:0) significantly increased the cfNRI of cardiovascular  complex end points in the metformin group and all participants by 74% and 55%, respectively (P=0.012, P=0.005).  Conclusion · Of 119 lipid components measured with LC-QTOF/ MS, baseline ChE (20:4) is a protective factor and SM (d18:1-22:0) is a risk factor for cardiovascular  complex end points in with T2DM and CHD patients after long-term treatment with metformin and glipizide. Both lipid components are helpful for improving the prediction of recurrent cardiovascular events.

Key words: type 2 diabetes, cardiovascular disease, lipid profiles, metformin, glipizide