期刊
JOURNAL OF DIABETES AND ITS COMPLICATIONS
卷 34, 期 5, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2020.107554
关键词
Type 2 diabetes; Cardiac MRI; Translational research; Animal models; Cardiac and hepatic functions
资金
- FCT - Portuguese national funding agency for science, research and technology [grant PAC - MEDPERSYST] [POCI-01-0145-FEDER-016428]
- FCT - Portuguese national funding agency for science, research and technology [grant COMPETE2020] [POCI 030852]
- FCT - Portuguese national funding agency for science, research and technology [grant BIGDATIMAGE - Centro 2020 FEDER] [CENTRO-01-0145-FEDER-000016]
- FCT - Portuguese national funding agency for science, research and technology [grant COMPETE] [FCT-UID/4539/2013 -COMPETE, POCI-01-0145-FEDER-007440]
- European Foundation for the Study of Diabetes - SANOFI grant
- [INFARMED - FIS-2015-01]
Background: The success of translational research depends on how well animal models mimic the pathophysiology of the human phenotype, and on the identification of disease mechanisms such as enhanced glycation. Methods: Here, we studied cardiac MRI and metabolic phenotypes in human type 2 diabetes (N = 106; 55 patients+51 controls) and animal models with distinct levels of fat diet and end glycation products, to model the role of these factors in the cardiac phenotype. We included four groups of rats, designed to evaluate the role of lipid load and glucotoxicity in cardiac function and to correlate these with the cardiac phenotype observed in humans. We also aimed to assess into which extent phenotypes were related to specific risk factors. Results: Stroke Volume (SV) and Peak Filling Rate (PFR) measures were similarly discriminative both in humans and animal models, particularly when enhanced glycation was present. Factorial analysis showed that reduction of multidimensionality into common main explanatory factors, in humans and animals, revealed components that equally explained the variance of cardiac phenotypes (87.62% and 83.75%, respectively). One of the components included, both in humans and animals, SV, PFR and peak ejection rate (PER). The other components included in both humans and animals are the following: ESV (end systolic volume), left ventricular mass (LVM) and ejection fraction (EF). These components were useful for between group discrimination. Conclusions: We conclude that animal models of enhanced glycation and human type 2 diabetes share a striking similarity of cardiac phenotypic components and relation with metabolic changes, independently of fact content in the diet, which reinforces the role of glucose dysmetabolism in left ventricular dysfunction and provides a potentially useful approach for translational research in diabetes, in particular when testing new therapies early on during the natural history of this condition. (C) 2020 Elsevier Inc. All rights reserved.
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