**7. Conclusion**

CVDs are considered as the leading cause of deaths globally and they are multifactorial in nature affecting the heart, the blood vessels and the blood. The flow diagram in **Figure 1** reveals the processes and mechanism(s) whereby diabetesinduced elevated hyperglycemia, hyperinsulinemia and hyperlipidemia can lead to oxidative stress, inflammation, mitochondrial dysfunction and other mechanisms, all resulting in cardiac dysfunction, including HF, DCM ,arrhythmias and sudden cardiac death., Initially, these dysfunctions are induced at the cellular, sub-cellular and molecular levels in the heart and they include changes in size, shape and function of the myocardium, including cellular calcium homeostasis. If the heart is left untreated, then it can develop, hypertrophy and disarray of the myofilaments and subsequently apoptosis and infiltration of fibrosis leading to remodeling of the myocardium. Moreover, chronic inflammation associated with cardiac dysfunction

**103**

**Figure 1.**

*Inflammation and Diabetic Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.88149*

can also result in damage and subsequent failure to a number of organs in the body including the heart and kidneys where the dynamics of blood flow is disturbed. In relation to the myocardium, there is an increase in CAPD and subsequently elevated diastolic [Ca2+]. The end-result is a delay in contraction and blood ejection from the heart. This leads to slower relaxation and filling process in the heart. Over time, the whole process will lead to a weak heart or DCM and subsequently, death of the patient. The cellular and molecular mechanisms associated with chronic inflammation and the cardiovascular system are not fully known and the literature suggests the need for further research into novel inflammatory markers of CVD risk.

*Changes occurring in the heart during diabetic cardiomyopathy. DCM in turn can lead to structural and* 

*functional changes at cellular and subcellular levels in the myocardium.*

*Inflammation and Diabetic Cardiomyopathy DOI: http://dx.doi.org/10.5772/intechopen.88149*

#### **Figure 1.**

*Inflammatory Heart Diseases*

is a known factor for ECD [56].

failure [47, 48]. The first target of HG-induced damage is the microvasculature. As a result, the small blood vessels will initiate a systematic complication [49, 50]. Increased oxidative stress (OS) is a key contributor to HG-induced diabetic damages [51]. Increased OS is a possible biochemical mechanism linking the onset of DM and its complications due to OS [52–54]. Furthermore, hypertrophy and myocardial fibrosis are also associated with endothelial cell dysfunction (ECD), inflammation and abnormal vascular remodelling seen in DCM [45]. The activation of endothelial cells (ECs) from a quiescent phenotype to vasoconstriction, pro-inflammatory and pro-apoptotic state can also result in ECD [55]. The exposure of the blood vessels to high fluctuating levels of elevated blood glucose (HG)

An increase in myocardial stiffness is an early sign in the pathogenesis of DCM. This increase in myocardial tissue stiffness is a result of increased collagen production by fibroblasts along with the fibrotic replacement of apoptotic/necrotic cells [57]. Collagen type I and type III fibres accumulate in the epicardial (EPI) layer of the heart and perivascular domains, whereas type IV is mostly found in the endocardial (ENDO) layer of the myocardium [58]. The increased stiffness in diabetic hearts may be due to an increase in the stiffness of cardiac myocytes within the myocardium. Although the changes in stiffness are not dramatic, they may be enough to cause or to contribute to increased cardiac workload over time, leading to DCM progression [59]. At the molecular level, DCM leads to prolongation and enhanced temporal dispersion of the repolarization phase of cardiac action potential (CAP) in myocytes leading to alterations of the spatial heterogeneity of ion channel expression and AP duration [60]. The major recognised factors of DCM are insulin resistance (IR) and hyperinsulinemia [61]. A disruption of insulin-mediated glucose metabolism occurs during IR and hyperinsulinemia which can significantly alter the efficiency of metabolism in cardiac muscle as well as skeletal muscle. The diabetic heart is affected by insulin in both systematic metabolism abnormalities via direct effects on insulin signalling pathways in the myocardium [62]. The early recognised change in insulin resistance in the heart is the impaired ability of insulin to increase glucose transport [63]. Recently, it was found that IR is linked to cardiac contractile dysfunction. In addition, a previous study, has developed a new IR rat model in which the animals were fed on a high cholesterol fructose (HCF) diet [63]. These results demonstrate that IR is directly linked to biochemical changes in the heart, thereby contributing to the development of DCM. Despite the recent advances in this field, our understanding of the initiation and progress of DCM is

CVDs are considered as the leading cause of deaths globally and they are multifactorial in nature affecting the heart, the blood vessels and the blood. The flow diagram in **Figure 1** reveals the processes and mechanism(s) whereby diabetesinduced elevated hyperglycemia, hyperinsulinemia and hyperlipidemia can lead to oxidative stress, inflammation, mitochondrial dysfunction and other mechanisms, all resulting in cardiac dysfunction, including HF, DCM ,arrhythmias and sudden cardiac death., Initially, these dysfunctions are induced at the cellular, sub-cellular and molecular levels in the heart and they include changes in size, shape and function of the myocardium, including cellular calcium homeostasis. If the heart is left untreated, then it can develop, hypertrophy and disarray of the myofilaments and subsequently apoptosis and infiltration of fibrosis leading to remodeling of the myocardium. Moreover, chronic inflammation associated with cardiac dysfunction

**102**

still very limited.

**7. Conclusion**

*Changes occurring in the heart during diabetic cardiomyopathy. DCM in turn can lead to structural and functional changes at cellular and subcellular levels in the myocardium.*

can also result in damage and subsequent failure to a number of organs in the body including the heart and kidneys where the dynamics of blood flow is disturbed. In relation to the myocardium, there is an increase in CAPD and subsequently elevated diastolic [Ca2+]. The end-result is a delay in contraction and blood ejection from the heart. This leads to slower relaxation and filling process in the heart. Over time, the whole process will lead to a weak heart or DCM and subsequently, death of the patient. The cellular and molecular mechanisms associated with chronic inflammation and the cardiovascular system are not fully known and the literature suggests the need for further research into novel inflammatory markers of CVD risk.

*Inflammatory Heart Diseases*
