Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
Department of Surgical, Medical Molecular Pathology and Critical Care Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
Cardiovasc Diabetol. 2019 May 10;18(1):61. doi: 10.1186/s12933-019-0865-6.
The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM).
In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s') and early diastolic (e') longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12.
T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e' velocity (P < 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01-0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects.
This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.
2 型糖尿病（T2DM）患者的血脂异常、炎症和心血管（CV）器官损伤之间的关系很复杂。胰岛素抵抗和炎症细胞因子白细胞介素（ILs）会增加血浆甘油三酯（TG）。ILs 还会上调基质金属蛋白酶（MMPs）的表达，这些 MMPs 与 TG 一起降低高密度脂蛋白胆固醇（HDL）水平。高 TG、低 HDL、高 ILs 和 MMPs 会引发不同部位的心血管系统的结构和功能变化。为了更好地理解脂质和炎症在心血管器官损伤中的作用，本研究调查了脂质、ILs 和 MMPs 之间的相互关系，以及脂质、ILs 和 MMPs 与糖尿病和非糖尿病患者（非 T2DM）的各种心血管指标之间的关联。
在 T2DM 患者（N=191）和非 T2DM 受试者（N=94）中，评估了颈动脉内膜中层厚度（cIMT）和内中膜厚度（IADiam）、颈动脉波速（ccaWS）、颈动脉-股动脉脉搏波速度（cfPWV）、左心室（LV）质量、LV 收缩期（s'）和二尖瓣环早期舒张期（e'）纵向速度，同时还评估了血糖控制、血脂谱、IL-6、IL-18 和 MMP-12。
与非 T2DM 受试者相比，T2DM 患者的血浆 IL-6、IL-18、MMP-12 水平显著升高，HDL 水平显著降低（P<0.05-0.0001）。T2DM 患者的 cIMT、IADiam、ccaWS、cfPWV 和 LV 质量也更高，而 e'速度更低（P<0.005-0.0001）。在 T2DM 患者和非 T2DM 受试者中，MMP-12 均随 IL-6（r=0.43 和 0.39；P<0.0001）和 IL-18（r=0.32 和 0.42；P<0.0001）的增加而增加，而 HDL 随 MMP-12 的减少而减少（r=-0.29 和-0.42；P<0.0001）。在这两个群体中，MMP-12 与 IADiam、ccaWS、cfPWV 和 LV 质量直接相关（r=0.42、0.32、0.26 和 0.29；在 T2DM 患者中 P<0.0001，r=0.39、0.28、0.32 和 0.27；在非 T2DM 受试者中 P<0.01-0.0001）。在多元分析中，MMP-12 在 T2DM 患者中与 IADiam、ccaWS、cfPWV 和 LV 质量仍呈独立相关，在非 T2DM 受试者中仅与 IADiam 相关。
这项横断面研究表明，ILs 和 MMP-12 之间存在直接关联，MMP-12 和 HDL 之间存在反向关联，这在 T2DM 患者和非 T2DM 受试者中均存在。在 T2DM 患者中，ILs 和 MMP-12 水平较高，后者与多种临床前心血管器官损伤的结构和功能标志物独立相关。
