PMID- 31077210
OWN - NLM
STAT- MEDLINE
DCOM- 20191230
LR  - 20200309
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 18
IP  - 1
DP  - 2019 May 10
TI  - Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and 
      inflammation.
PG  - 61
LID - 10.1186/s12933-019-0865-6 [doi]
LID - 61
AB  - 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.
FAU - Kozakova, Michaela
AU  - Kozakova M
AD  - Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 
      10, 56126, Pisa, Italy.
FAU - Morizzo, Carmela
AU  - Morizzo C
AD  - Department of Surgical, Medical Molecular Pathology and Critical Care Medicine, 
      University of Pisa, Via Savi 10, 56126, Pisa, Italy.
FAU - Goncalves, Isabel
AU  - Goncalves I
AD  - Department of Clinical Sciences Malmo, Lund University, Jan Waldenstroms gata 35, 
      20502, Malmo, Sweden.
FAU - Natali, Andrea
AU  - Natali A
AD  - Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 
      10, 56126, Pisa, Italy.
FAU - Nilsson, Jan
AU  - Nilsson J
AD  - Department of Clinical Sciences Malmo, Lund University, Jan Waldenstroms gata 35, 
      20502, Malmo, Sweden.
FAU - Palombo, Carlo
AU  - Palombo C
AUID- ORCID: 0000-0002-0628-2729
AD  - Department of Surgical, Medical Molecular Pathology and Critical Care Medicine, 
      University of Pisa, Via Savi 10, 56126, Pisa, Italy. carlo.palombo@unipi.it.
LA  - eng
PT  - Journal Article
DEP - 20190510
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukins)
RN  - 0 (Lipids)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Aged
MH  - Biomarkers/blood
MH  - Carotid Artery Diseases/blood/diagnostic imaging/*etiology/physiopathology
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Diabetes Mellitus, Type 2/blood/*complications/diagnosis
MH  - Diabetic Angiopathies/blood/diagnostic imaging/*etiology/physiopathology
MH  - Diabetic Cardiomyopathies/blood/diagnostic imaging/*etiology/physiopathology
MH  - Dyslipidemias/blood/*complications/diagnosis
MH  - Female
MH  - Humans
MH  - Inflammation/blood/*complications/diagnosis
MH  - Inflammation Mediators/*blood
MH  - Interleukins/blood
MH  - Lipids/*blood
MH  - Male
MH  - Matrix Metalloproteinases/blood
MH  - Middle Aged
MH  - Risk Factors
MH  - Vascular Remodeling
MH  - Ventricular Remodeling
PMC - PMC6511166
OTO - NOTNLM
OT  - Arterial stiffness
OT  - Diabetes mellitus
OT  - High density lipoprotein cholesterol
OT  - Interleukins
OT  - Left ventricular mass
OT  - Matrix-metalloproteinase
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The protocol of the study was 
      approved by the ethics committee "Comitato Etico Area Vasta Nord-Ovest" 
      (Reference Number: 3146/2010). CONSENT FOR PUBLICATION: Not applicable. COMPETING 
      INTERESTS: M Kozakova is responsible for Clinical Studies in Esaote, SpA, Genova, 
      Italy.
EDAT- 2019/05/12 06:00
MHDA- 2019/12/31 06:00
PMCR- 2019/05/10
CRDT- 2019/05/12 06:00
PHST- 2019/01/25 00:00 [received]
PHST- 2019/05/02 00:00 [accepted]
PHST- 2019/05/12 06:00 [entrez]
PHST- 2019/05/12 06:00 [pubmed]
PHST- 2019/12/31 06:00 [medline]
PHST- 2019/05/10 00:00 [pmc-release]
AID - 10.1186/s12933-019-0865-6 [pii]
AID - 865 [pii]
AID - 10.1186/s12933-019-0865-6 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2019 May 10;18(1):61. doi: 10.1186/s12933-019-0865-6.