Elsevier

International Journal of Cardiology

Volume 217, 15 August 2016, Pages 195-204
International Journal of Cardiology

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus

https://doi.org/10.1016/j.ijcard.2016.04.178Get rights and content

Highlights

  • Different pathophysiologic mechanisms between type 1 and type 2 diabetes are proposed.

  • Type 1 diabetes induced higher biventricular hypertrophy and fibrosis.

  • Type 2 diabetes promoted dysfunction, namely impaired right ventricular relaxation.

  • Pressure overload deteriorated cardiac function but only in type 2 diabetes.

Abstract

Background

Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload.

Methods

Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5 weeks of DM the cardiac function and structure were evaluated.

Results

Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle.

Conclusions

Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population.

Section snippets

Background

Diabetes mellitus (DM) is a chronic metabolic disease that results from pancreas' inability to produce insulin, such as in Type 1 DM (T1DM), or from the incapacity of the organs to use insulin, as in Type 2 DM (T2DM). This impairment of insulin production and/or utilization and consequent hyperglycemia instigates multiple organ failure, including those of the cardiovascular system [1]. The incidence of diabetes mellitus has dramatically increased worldwide and in the next years the number of

Experimental animal model

This study was made according to the Guide for the Care and Use of Laboratory Animals published by the NIH (NIH Publication no. 85-23, revised 2011) and with the Portuguese law of animal welfare (DL 129/92, DL 197/96; P 1131/97). The Faculty of Medicine of the Universidade do Porto is a governmental institution granted with approval to perform animal experiments by the Portuguese Government.

Male Wistar Han rats were obtained from Charles River (Spain) and housed in groups of 5 per cage in a

Morphometric characterization

All animals with T1DM presented lower BW but increased heart, lung and renal indexed weight (Table 3). The simultaneous presence of pressure overload had no impact in the parameters mentioned before. The ingestion of a HCD for 5 weeks did not alter body weight of the DM2 animals, neither the weight of other organs analyzed. On the contrary, the DB2 group presented cardiac hypertrophy and evidences of lung congestion.

Cardiac structure

Echocardiographic results of both protocols are summarized in Fig. 1. The

Discussion

Since the recognition of diabetic cardiomyopathy in the 1970s [20], researchers have tried to unravel the mechanisms instigating this disease. However, the majority of the papers focus their attention in one type of DM and in one ventricle, neglecting the importance of the RV for myocardial function. In our study we used two well-known animal models of DM and compared the magnitude of the biventricular adaptations triggered either by T1DM or T2DM. Furthermore, since the prevalence of

Conclusion

In conclusion, our study demonstrates that both types of diabetes induce distinct cardiac alterations per se and when combined with chronic pressure overload. The T1DM promotes a more pronounced hypertrophy and extracellular matrix remodeling, whereas T2DM has higher impact in myocardial function, either in the LV as in the RV. The simultaneous presence of pressure overload had cardiac repercussions only in the DB2 group, impairing biventricular systolic and diastolic functions.

Funding

This work was supported by Portuguese Foundation for Science and Technology Grant UID/IC/00051/2013 financed with national funds by Fundação para a Ciência e Tecnologia and by Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI), EXCL-II/BIM-MEC/0055/2012, and by European Commission Grant FP7-Health-2010, MEDIA-261409. This work was supported by Portuguese Foundation for Science and Technology Grant SFRH/BD/66628/2009

Competing and conflicting interests

The authors declare that they have no conflict of interests.

Author contribution

Nádia Gonçalves: conception and design of research; performed experiments; analyzed data; interpreted results of experiments; prepared figures; drafted manuscript, approved final version of manuscript.

Carla Gomes-Ferreira: performed experiments; analyzed data; prepared figures; drafted manuscript, approved final version of manuscript.

Cláudia Moura: performed experiments; analyzed data, approved final version of manuscript.

Roberto Roncon-Albuquerque Jr: conception and design of research;

Acknowledgments

The authors thank Ana Filipa Silva and Cláudia Mendes for the cardiac histological evaluation and Patrícia Gonçalves Rodrigues for isolated cardiomyocyte's analysis. The authors thank André Lourenço for the statistical analysis.

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    All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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    These authors contributed equally to this work.

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