Diabetic heart disease: A clinical update

Abstract

Diabetes mellitus (DM) significantly increases the risk of heart disease, and DM-related healthcare expenditure is predominantly for the management of cardiovascular complications. Diabetic heart disease is a conglomeration of coronary artery disease (CAD), cardiac autonomic neuropathy (CAN), and diabetic cardiomyopathy (DCM). The Framingham study clearly showed a 2 to 4-fold excess risk of CAD in patients with DM. Pathogenic mechanisms, clinical presentation, and management options for DM-associated CAD are somewhat different from CAD among nondiabetics. Higher prevalence at a lower age and more aggressive disease in DM-associated CAD make diabetic individuals more vulnerable to premature death. Although common among diabetic individuals, CAN and DCM are often under-recognised and undiagnosed cardiac complications. Structural and functional alterations in the myocardial innervation related to uncontrolled diabetes result in damage to cardiac autonomic nerves, causing CAN. Similarly, damage to the cardiomyocytes from complex pathophysiological processes of uncontrolled DM results in DCM, a form of cardiomyopathy diagnosed in the absence of other causes for structural heart disease. Though optimal management of DM from early stages of the disease can reduce the risk of diabetic heart disease, it is often impractical in the real world due to many reasons. Therefore, it is imperative for every clinician involved in diabetes care to have a good understanding of the pathophysiology, clinical picture, diagnostic methods, and management of diabetes-related cardiac illness, to reduce morbidity and mortality among patients. This clinical review is to empower the global scientific fraternity with up-to-date knowledge on diabetic heart disease.

Keywords: Cardiac autonomic neuropathy; Cardiovascular disease; Coronary artery disease; Diabetic cardiomyopathy; Diabetic heart disease; Type 1 diabetes mellitus; Type 2 diabetes mellitus.

Figure 1

Pathophysiology of coronary artery disease in diabetes. AGE: Advanced glycation end products; RAGE: Receptors for AGE; LDL: Low density lipoprotein; ROS: Reactive oxygen species; PKC: Protein kinase C; HBP: Hexosamine biosynthetic pathway; MCP-1: Monocyte chemotactic pLrotein-1; VCAM-1: Vascular cell adhesion molecule 1; TGF-β: Transforming growth factor-β; ECM: Extracellular Matrix.

Figure 2

Pathophysiology of cardiac autonomic neuropathy in diabetes. PARP: Polyadenosine-diphosphate-ribose polymerase; AMPK: Adenosine monophosphate-activated protein kinase; ER: Endoplasmic reticulum; ROS: Reactive oxygen species; NADPH: Nicotinamide adenine dinucleotide phosphate; AGE: Advanced glycation end products; RAGE: Receptors for AGE; LDL: Low density lipoprotein; LCSFA: Long chain saturated fatty acid.

Figure 3

Pathophysiology of diabetic cardiomyopathy. NADPH: Nicotinamide adenine dinucleotide phosphate; ROS: Reactive oxygen species; GLUT: Glucose transporter; ER: Endoplasmic reticulum; SR: Sarcoplasmic reticulum; NF-kB: Nuclear factor-kB; TNF-α: Tumour necrosis factor-α; IL-6: Interleukin-6; IL-8: Interleukin-8; AGE: Advanced glycation end products; RAGE: Receptors for AGE; MHC: Myosin heavy chain; ANP: Atrial natriuretic peptide; BNP: Brain natriuretic peptide; TGF-β: Transforming growth factor-β; ECM: Extracellular matrix; NO: Nitric oxide; EDHF: Endothelium-derived hyperpolarising factor; ATP: Adenosine triphosphate; AP-1: Activator protein-1; BP: Blood pressure; DAG: Diacyl glycerol; FA: Fatty acid; CAN: Cardiac autonomic neuropathy; RAAS: Renin-angiotensin-aldosterone system.

Figure 4

Pathophysiology and clinical presentation of diabetic heart disease. AGE: Advanced glycation end products; RAGE: Receptors for AGE; HFpEF: Heart failure with preserved ejection fraction; HFrEF: Heart failure with reduced ejection fraction; CAN: Cardiac autonomic neuropathy; CAD: Coronary artery disease; DCM: Diabetic cardiomyopathy.