Mechanisms of diabetic cardiomyopathy: Focus on inflammation

FIGURE 1. Natural history of diabetic cardiomyopathy. Hyperglycemia, insulin resistance and hyperinsulinemia induce cardiac insulin resistance and metabolic disorders that increase mitochondrial dysfunction (1), oxidative stress (2) and cytokine secretion (3). Other risk factors enhance metabolic derangements in cardiomyocytes, including increased free fatty acids oxidation, lipotoxicity and lipid accumulation within cardiomyocytes (4). These pathophysiological abnormalities promote fibroblast recruitment (5) and myocardial fibrosis (6), resulting in cardiac diastolic dysfunction, systolic dysfunction and heart failure. ROS, reactive oxygen species; TNFα, tumour necrosis factor α. Figure created with BioRender.com.

FIGURE 2. Pathophysiological mechanisms of diabetic cardiomyopathy. Hyperglycemia and insulin resistance induce cardiac insulin resistance and metabolic disorders that increase mitochondria dysfunction, oxidative stress, impairment of mitochondria Ca2+ handling and inflammation. Increased free fatty acid oxidation and AGE production promote myocardial fibrosis and dysfunction. AGE, advanced glycation end product; ECM, extracellular membrane; FFA, free fatty acids; NLRP3, nucleotide oligomerization domain (NOD)‐like receptor containing pyrin domain 3; RAAS, renin‐angiotensin‐aldosterone system; RAGE, advanced glycation end product receptor. Figure created with BioRender.com.

FIGURE 3. A simplified algorithm for assessing individuals with type 2 diabetes at risk of developing diabetic cardiomyopathy. CAD, coronary artery disease; CMR, cardiac magnetic resonance imaging; CV, cardiovascular; Gal‐3, galactin‐3; h‐s CRP, high‐sensitivity C‐reactive protein; IL‐6, interleukin‐6; LV, left ventricular; PET, positron emission tomography; sST2, soluble suppression of tumorigenesis‐2; T2DM, type‐2 diabetes mellitus. Figure created with BioRender.com.

FIGURE 4. A streamlined overview of current recommendations for individuals with type‐2 diabetes at different stages of HF. ACEi, angiotensin‐converting enzyme inhibitor; ARBs, angiotensin II receptor blockers; CRT, cardiac resynchronization therapy; CV, cardiovascular; GDMT, guideline‐directed medical therapy; GLP‐1RA, glucagon‐like peptide‐1 receptor agonists; HF, heart failure; LVAD, left ventricular assist device; RAASi, renin‐angiotensin‐aldosterone system inhibitors; SGLT2‐i, sodium‐glucose cotransporter‐2 inhibitors. Figure created with BioRender.com.