The diabetic cardiomyopathy

Abstract

Diabetic cardiomyopathy has been defined as "a distinct entity characterized by the presence of abnormal myocardial performance or structure in the absence of epicardial coronary artery disease, hypertension, and significant valvular disease". The diagnosis stems from the detection of myocardial abnormalities and the exclusion of other contributory causes of cardiomyopathy. It rests on non-invasive imaging techniques which can demonstrate myocardial dysfunction across the spectra of clinical presentation. The presence of diabetes is associated with an increased risk of developing heart failure, and the 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. Diabetic patients with microvascular complications show the strongest association between diabetes and cardiomyopathy, an association that parallels the duration and severity of hyperglycemia. Metabolic abnormalities (that is hyperglycemia, hyperinsulinemia, and hyperlipemia) can lead to the cellular alterations characterizing diabetic cardiomyopathy (that is myocardial fibrosis and/or myocardial hypertrophy) directly or indirectly (that is by means of renin-angiotensin system activation, cardiac autonomic neuropathy, alterations in calcium homeostasis). Moreover, metabolic abnormalities represent, on a clinical ground, the main therapeutic target in the patients with diabetes since the diagnosis of diabetes is made. Since diabetic cardiomyopathy is highly prevalent in the asymptomatic type 2 diabetic patients, screening for its presence at the earliest stage of development can lead to prevent the progression to chronic heart failure. The most sensitive test is standard echocardiogram, while a less expensive pre-screening method is the detection of microalbuminuria.

Diabetic cardiomyopathy

“…Advanced glycation end-products (AGEs) which are thought to contribute to arterial and myocardial stiffness, endothelial dysfunction, and atherosclerosis plaque formation, increases in diabetic patients (7,8,15,16). Extracellular proteins, such as collagen and elastin, are particularly vulnerable to accumulation of AGE crosslink (17).…”

“…Crosslinks in collagen and elastin cause increased myocardial stiffness and impaired cardiac relaxation (4). Also AGEs aggravate intracellular oxidative stress which can contribute to cell damage (15,16,18). In addition, hyperglycemia activates local renin-angiotensin-aldosterone system (RAAS), contributing to myocyte necrosis and fibrosis (8,19,20).…”

“…In addition, hyperglycemia activates local renin-angiotensin-aldosterone system (RAAS), contributing to myocyte necrosis and fibrosis (8,19,20). To maintain glucose homeostasis, insulin levels increase compensatory and due to the similarities in the extracellular domains between the insulin receptor and the insulin-like growth factor IGF 1 receptor, increased levels of insulin can promote cellular hypertrophy by binding to the IGF-1 receptor so that insulin acts as growth factor on myocytes (15,21). Hyperglycemia and hyperinsulinemia stimulate overexpression of transforming growth factor-1 by cardiac fibroblasts, resulting in fibrous tissue deposition and extracellular matrix synthesis (8,22).…”

“…FFA's inhibit pyruvate dehydrogenase and leads to accumulation of glycolytic intermediates and ceramides, which enhance apoptosis (2,25). In addition, FFA metabolism for adenosine triphosphate production requires large amounts of oxygen that results in more toxic intermediates (lipotoxicity) which impair myocyte calcium handling, worsening myocardial mechanics (8,15,23,(26)(27)(28)(29).…”

Insulin and IGF1 receptors in human cardiac microvascular endothelial cells: metabolic, mitogenic and anti-inflammatory effects

“…The development of these complications is dependent on the integrity and function of the endothelium (Kim et al 2006, Pambianco et al 2006. There is a strong association between microvascular complications and cardiomyopathy leading to heart failure (Tarquini et al 2010). Alterations in the insulinlike growth factor (IGF) system have been demonstrated in diabetic patients when compared with healthy individuals (Bereket et al 1999, Delafontaine et al 2004, Hedman et al 2004.…”