Advanced glycation end‐products (AGEs) and heart failure: Pathophysiology and clinical implications

Abstract

Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes, AGE accumulation is associated with the development of cardiac dysfunction. Enhanced AGE accumulation is not restricted to patients with diabetes, but can also occur in renal failure, enhanced states of oxidative stress, and by an increased intake of AGEs. Several lines of evidence suggest that AGEs are related to the development and progression of heart failure in non-diabetic patients as well. Preliminary small intervention studies with AGE cross-link breakers in heart failure patients have shown promising results. In this review, the role of AGEs in the development of heart failure and the role of AGE intervention as a possible treatment for heart failure are discussed.

Neurohormonal profile of patients with heart failure and diabetes

“…However, increased insight into the pathophysiology of these diseases has also led to increased awareness and recognition of diastolic dysfunction. 22 Accumulation of advanced glycation end-products (AGE)s, which occurs in diabetes, hypertension, but also in ageing, may potentially play a role in the development of diastolic dysfunction, 23 but whether this may have therapeutic consequences is so far unknown, and indeed, the treatment of diastolic heart failure in the presence or absence of diabetes is hampered by the absence of evidence for a specific drug that can reduce mortality and morbidity in these patients. 24 While BNP (and to a lesser extent N-terminal (pro)BNP) were increased in HF patients with diabetes, it was remarkable that all other neurohormones were similar.…”

Functional Effects of Alagebrium (ALT-711)–Isolated Rat Carotid Artery

“…Because, intracellular Ca +2 homeostasis is a key factor for the connection between excitation and contraction and altered Ca +2 homeostasis in diabetes mellitus has been associated with the impairment in myocardial contractility and relaxation [18]. However, previous studies have failed to reveal the exact mechanisms underlying the impaired Ca +2 homeostasis as well as to define specific therapeutic targets for these patients [18,19].…”

Glycated albumin and glycated hemoglobin- A comparison

“…Diabetes monitoring for protein glycation, an essential element for the long-term control of the complications of diabetes mellitus, is currently managed by a combination of daily self-monitoring of blood glucose (SMBG) measurements and physician-assessed hemoglobin A1c (A1C) levels every 3-6 months. 4,5,6,7,8 Figure I-Factors involved in pathogenesis of Diabetic Nephropathy…”