Pathophysiology and Advances in the Therapy of Cardiomyopathy in Patients with Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is known as the first non-communicable global epidemic. It is estimated that 537 million people have DM, but the condition has been properly diagnosed in less than half of these patients. Despite numerous preventive measures, the number of DM cases is steadily increasing. The state of chronic hyperglycaemia in the body leads to numerous complications, including diabetic cardiomyopathy (DCM). A number of pathophysiological mechanisms are behind the development and progression of cardiomyopathy, including increased oxidative stress, chronic inflammation, increased synthesis of advanced glycation products and overexpression of the biosynthetic pathway of certain compounds, such as hexosamine. There is extensive research on the treatment of DCM, and there are a number of therapies that can stop the development of this complication. Among the compounds used to treat DCM are antiglycaemic drugs, hypoglycaemic drugs and drugs used to treat myocardial failure. An important element in combating DCM that should be kept in mind is a healthy lifestyle-a well-balanced diet and physical activity. There is also a group of compounds-including coenzyme Q10, antioxidants and modulators of signalling pathways and inflammatory processes, among others-that are being researched continuously, and their introduction into routine therapies is likely to result in greater control and more effective treatment of DM in the future. This paper summarises the latest recommendations for lifestyle and pharmacological treatment of cardiomyopathy in patients with DM.

Keywords: DCM; DM; GLP-1 analogues; SGLT2 inhibitors; diabetes mellitus; diabetic cardiomyopathy; healthy lifestyle; heart failure; inflammation; metformin; reactive oxygen species; thiazolidinediones.

Figure 1

Multifactorial disorders in diabetic cardiomyopathy. Abbreviations: AGEs—advanced glycation end products; RAGE—receptor advanced glycation end product; RAAS—renin–angiotensin–aldosterone system; and SNS—sympathetic nervous system.

Figure 2

(a) Molecular proteins and signalling pathways in DCM—part 1. (b) Molecular proteins and signalling pathways in DCM—part 2. Abbreviations: TGF-β—transforming growth factor β; PI3K—phosphoinositide 3-kinases; ERK—extracellular signal-regulated kinase; Ki-RAS—Kirsten RAS; SERCA2a—sarcoendoplasmic reticulum Ca²⁺-ATPase 2a; NF-κB—nuclear factor kappa B; Nrf-2—nuclear factor erythroid 2-related factor 2; Sirt 1—sirtuin 1; RNA—ribonucleic acid; DNA—deoxyribonucleic acid; AGEs—advanced glycation end products; RAGE—receptor advanced glycation end product; ROS—reactive oxygen species; O₂^•−—superoxide ion; HO₂^•—hydroperoxyl radical; HO^•—hydroxyl radical; RO^•—alkoxy radical; ¹O₂—singlet oxygen; H₂O₂—hydrogen peroxide; NADPH—nicotinamide adenine dinucleotide phosphate; LYMPH—lymphocyte; MONO—monocyte; CRP—C-reactive protein; PKC—protein kinase C; FN—fibronectin; and NO—nitric oxide.

Figure 2

(a) Molecular proteins and signalling pathways in DCM—part 1. (b) Molecular proteins and signalling pathways in DCM—part 2. Abbreviations: TGF-β—transforming growth factor β; PI3K—phosphoinositide 3-kinases; ERK—extracellular signal-regulated kinase; Ki-RAS—Kirsten RAS; SERCA2a—sarcoendoplasmic reticulum Ca²⁺-ATPase 2a; NF-κB—nuclear factor kappa B; Nrf-2—nuclear factor erythroid 2-related factor 2; Sirt 1—sirtuin 1; RNA—ribonucleic acid; DNA—deoxyribonucleic acid; AGEs—advanced glycation end products; RAGE—receptor advanced glycation end product; ROS—reactive oxygen species; O₂^•−—superoxide ion; HO₂^•—hydroperoxyl radical; HO^•—hydroxyl radical; RO^•—alkoxy radical; ¹O₂—singlet oxygen; H₂O₂—hydrogen peroxide; NADPH—nicotinamide adenine dinucleotide phosphate; LYMPH—lymphocyte; MONO—monocyte; CRP—C-reactive protein; PKC—protein kinase C; FN—fibronectin; and NO—nitric oxide.