Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

Abstract

Background 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). Methods 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (10.1186/s12933-019-0865-6) contains supplementary material, which is available to authorized users.

Positive association between triglyceride glucose index and arterial stiffness in hypertensive patients: the China H-type Hypertension Registry Study

“…Although the exact mechanisms underlying the relationship of the TyG index with arterial stiffness is unclear, it may be linked to IR. IR is associated with hyperinsulinaemia, hyperglycaemia, dyslipidemia, hypertension and a proin ammatory state, as well as the effect of perturbed insulin signaling at the level of the intimal cells (endothelial cells, vascular smooth muscle cells, and macrophages), all of which predispose to arterial stiffness [13,[35][36][37][38]. In our study, men showed larger regression coe cients and odds ratios of the TyG index in relation with increased arterial stiffness than women.…”

Coagulatory Defects in Type-1 and Type-2 Diabetes

“…Furthermore, matrix metalloproteinases are zinc-binding proteinases that degrade components of the extracellular matrix and whose production is upregulated notably by hyperglycaemia, pro-inflammatory mediators and reactive oxygen species [150]. Matrix metalloproteinase levels are associated with cardiovascular disease development and all-cause mortality in T1DM [151][152][153], and with cardiovascular organ damage in T2DM [154]. In diabetes, they increase inflammation, endothelial dysfunction, vascular remodelling and thrombus formation [155,156].…”

The association between serum growth differentiation factor 15 levels and lower extremity atherosclerotic disease is independent of body mass index in type 2 diabetes

“…The results from previous studies have shown that increased circulating GDF15 levels were closely associated with the development and progression of various cardiovascular diseases (including myocardial ischaemia/reperfusion, heart failure, atherosclerosis, and acute coronary syndrome), and were shown to be a strong and independent predictor of mortality and disease progression in patients with atherosclerosis and coronary artery disease [5][6][7][8][9][10][31][32][33][34][35][36]. In diabetic patients, higher levels of lipids and chronic inflammation may directly damage the cardiovascular system [37]. As expected, circulating GDF15 levels have also been shown to help identify and predict cardiovascular disease risk in patients with diabetes [16,38,39].…”