Association of Advanced Glycation End Products (AGEs) with Diabetic Nephropathy and Alcohol Consumption

Abstract

The occurrence of diabetes is accelerating worldwide, with consequent increase in the secondary complication like diabetic nephropathy (DN). Diabetic nephropathy refers to a set of structural and functional abnormalities of kidney in patients with diabetes. Detrimental changes like glomerular hypertrophy, glomerulosclerosis, hyperfiltration, proteinuria, etc. occur in DN. One of the major pathways suggested for the pathogenesis is formation of Advanced Glycation End Products (AGEs) via non enzymatic glycation (NEG). NEG is the process in which reducing sugars irreversibly modify free amino groups of proteins, by various events leading to the formation of a Schiff base resulting in Amadori products, culminating into AGEs. AGEs activate several cascades of intracellular signaling via interaction with Receptor for AGEs (RAGE) that results in responses like release of pro-inflammatory cytokines resulting in inflammation, autophagy and programmed cell death. AGEs can also come into circulation from baked food and processed food items. AGEs can also be formed through various oxidative reactions, including the chronic use of alcohol. Alcohol in excess could result in accumulation of acetaldehyde that would lead to insulin resistance. Many risk factors like race, genetic susceptibility, hypertension, hyperglycemia, hyper filtration, smoking, advanced age, male sex, and high-protein diet account for development of DN. Therapeutic interventions include glycemic control, control of blood pressure. This review focuses on the formation of AGEs via non enzymatic glycation, its implications in pathogenesis of DN and therapies designed to break AGEs so as to prevent the development of DN.

Endogenous advanced glycation end products in the pathogenesis of chronic diabetic complications

“…Clinically, it is defined by the development of proteinuria, followed by a gradual reduction in the glomerular filtration rate over time. It is also a substantial risk factor for macrovascular problems if left untreated ( Parwani, 2017 ; Lin et al, 2018 ). AGE levels in renal tissue have been found to correlate with DN.…”

“…Angiotensin II causes mesangial and tubular epithelial cell hypertrophy and acts via the angiotensin II type 1 receptor (AT1R). AGEs, on the other hand, increase AT1R expression, which increases Angiotensin II activity ( Parwani, 2017 ).…”

Correlation of Dietary Advanced Glycation End Products with the Hematological and Biochemical Markers of Patients with Chronic Kidney Disease Undergoing Hemodialysis

“…It should be noted, however, that the high consumption of alcohol is linked with the formation of AGEs, insulin resistance, and secondary DM complications since acetaldehyde, one of the main metabolites of alcohol, when in excess, turns into a toxic substance, forming addition compounds with DNA, lipids, and proteins. Alcohol also tends to speed up the oxidative stress by reducing antioxidants such as vitamins A, C, and E, taking thus part in the formation of AGEs [15].…”

Microvascular Complications Associated with Advanced Glycation End Products in Diabetes

“…When it manifests medically, albuminuria starts to develop, while its GFR gradually decreases as time passes. It is also a substantial trigger factor in developing macrovascular problems if not controlled [25].…”