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

Kozakova, Michaela; Morizzo, Carmela; Goncalves, Isabel LU ; Natali, Andrea; Nilsson, Jan LU and Palombo, Carlo (2019) In Cardiovascular Diabetology 18(1).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Arterial stiffness, Diabetes mellitus, High density lipoprotein cholesterol, Interleukins, Left ventricular mass, Matrix-metalloproteinase
in
Cardiovascular Diabetology
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85065593971
ISSN
1475-2840
DOI
10.1186/s12933-019-0865-6
language
English
LU publication?
yes
id
22143f9d-6474-4fd6-988d-6b7b26386755
date added to LUP
2019-05-22 12:57:33
date last changed
2019-06-19 04:13:10
@article{22143f9d-6474-4fd6-988d-6b7b26386755,
  abstract     = {<p>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 &lt; 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e′ velocity (P &lt; 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P &lt; 0.0001) and IL-18 (r = 0.32 and 0.42; P &lt; 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P &lt; 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 &lt; 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P &lt; 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.</p>},
  articleno    = {61},
  author       = {Kozakova, Michaela and Morizzo, Carmela and Goncalves, Isabel and Natali, Andrea and Nilsson, Jan and Palombo, Carlo},
  issn         = {1475-2840},
  keyword      = {Arterial stiffness,Diabetes mellitus,High density lipoprotein cholesterol,Interleukins,Left ventricular mass,Matrix-metalloproteinase},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Cardiovascular Diabetology},
  title        = {Cardiovascular organ damage in type 2 diabetes mellitus : The role of lipids and inflammation},
  url          = {http://dx.doi.org/10.1186/s12933-019-0865-6},
  volume       = {18},
  year         = {2019},
}