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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-019-0865-6 |
| _version_ | 1811322981597577216 |
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| author | Michaela Kozakova Carmela Morizzo Isabel Goncalves Andrea Natali Jan Nilsson Carlo Palombo |
| author_facet | Michaela Kozakova Carmela Morizzo Isabel Goncalves Andrea Natali Jan Nilsson Carlo Palombo |
| author_sort | Michaela Kozakova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T13:46:01Z |
| format | Article |
| id | doaj.art-b9934a76631143bda36275e7dc0c068e |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-13T13:46:01Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-b9934a76631143bda36275e7dc0c068e2022-12-22T02:44:29ZengBMCCardiovascular Diabetology1475-28402019-05-0118111110.1186/s12933-019-0865-6Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammationMichaela Kozakova0Carmela Morizzo1Isabel Goncalves2Andrea Natali3Jan Nilsson4Carlo Palombo5Department of Clinical and Experimental Medicine, University of PisaDepartment of Surgical, Medical Molecular Pathology and Critical Care Medicine, University of PisaDepartment of Clinical Sciences Malmö, Lund UniversityDepartment of Clinical and Experimental Medicine, University of PisaDepartment of Clinical Sciences Malmö, Lund UniversityDepartment of Surgical, Medical Molecular Pathology and Critical Care Medicine, University of PisaAbstract 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.http://link.springer.com/article/10.1186/s12933-019-0865-6Diabetes mellitusInterleukinsMatrix-metalloproteinaseHigh density lipoprotein cholesterolArterial stiffnessLeft ventricular mass |
| spellingShingle | Michaela Kozakova Carmela Morizzo Isabel Goncalves Andrea Natali Jan Nilsson Carlo Palombo Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation Cardiovascular Diabetology Diabetes mellitus Interleukins Matrix-metalloproteinase High density lipoprotein cholesterol Arterial stiffness Left ventricular mass |
| title | Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation |
| title_full | Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation |
| title_fullStr | Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation |
| title_full_unstemmed | Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation |
| title_short | Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation |
| title_sort | cardiovascular organ damage in type 2 diabetes mellitus the role of lipids and inflammation |
| topic | Diabetes mellitus Interleukins Matrix-metalloproteinase High density lipoprotein cholesterol Arterial stiffness Left ventricular mass |
| url | http://link.springer.com/article/10.1186/s12933-019-0865-6 |
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