Fig. 1

Cardiac scenario in diabetic patients. Biomarkers discovery for DCM diagnosis. In diabetes, high levels of blood glucose and fatty-acid, together with a defect in insulin signalling (insulin resistance) activate diferent cellular mechanism in the myocardium. Glucose cannot be appropriately assimilated by cardiomyocyte and deviate to glucose metabolites such as AGEs (with ECM proteins), polyols and hexosamine, which may activate pro-oxidant and pro-inflammatory responses. Energy relies on FFA only, which are uptaken in excess and accumulated as secoundary toxic products such as TAG (in lipid droplets; LD), ceramide and DAG, leading to steatosis. They also decrease calcium flux between sarcoplasmic reticulum and cytosol, reducing actin-myosin-TnI/T complexes, and contractibility. FFA also bind PPAR receptors for upregulation of mitochondrial beta-oxidation enzymes, which produce non-efficient ATP and ROS, triggering mitochondrial dysfunction (release of cytochrome-C) and apoptosis. All these stimuli promote the expression specific miRNAs, and pro-hypertrophic and pro-fibrotic factors such as RAA and TGFβ systems, which may play autocrine and paracrine roles on (myo)fibroblast and adipocytes (from EAT). Interestingly, some of these molecules (in bold) can be released to the circulation and being used as biomarkers of cardiac dysfunction. UR unspecific receptor, TLRs toll-like receptors