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Advanced glycation end-products: a review
1Dept of Medicine, University of Western Australia and West Australian Heart Researrch Institute, Perth, Australia.
Abstract:
Advanced glycation end-products are a complex and heterogeneous group of compounds that have been implicated in diabetes related complications. At present it is not known if they are the cause or the consequence of the complications observed. We discuss the chemistry of advanced glycated end-product formation and their patho-biochemistry particularly in relation to the diabetic microvascular complications of retinopathy, neuropathy and nephropathy as well as their role in the accelerated vasculopathy observed in diabetes. The concept of carbonyl stress as a cause for advanced glycated end-product toxicity is mentioned. We discuss alterations in the concentrations of advanced glycated end-products in the body, particularly in relation to changes occurring with age, diabetes and its complications such as nephropathy. Problems relating to current methods of advanced glycated end-product detection and measurement are highlighted including the lack of a universally established method of detection or unit of measurement. Agents used for the treatment of advanced glycated end-product accumulation are reviewed, with an emphasis on the results of the recent phase III trials using aminoguanidine and diabetes related complications.
Insights
Advanced glycation end-products (AGEs) are linked to diabetes complications. This review explores AGE formation, their role in diabetic complications, and challenges in detection and treatment.
Area of Science:
- Biochemistry
- Endocrinology
- Pathology
Background:
- Advanced glycation end-products (AGEs) are implicated in diabetes complications, but their causal role remains unclear.
- AGEs are a heterogeneous group of compounds formed through non-enzymatic reactions.
- Their accumulation is associated with microvascular (retinopathy, neuropathy, nephropathy) and macrovascular complications in diabetes.
Purpose of the Study:
- To review the chemistry and pathobiochemistry of AGE formation.
- To discuss the role of AGEs in diabetic complications and the concept of carbonyl stress.
- To highlight challenges in AGE detection and measurement, and review therapeutic agents.
Main Methods:
- Literature review of AGE formation, biochemistry, and clinical relevance.
- Discussion of AGEs in the context of aging, diabetes, and its complications.
- Analysis of current detection methods and therapeutic strategies, including aminoguanidine trials.
Main Results:
- AGEs formation involves complex chemical reactions, contributing to diabetic complications.
- Carbonyl stress is a proposed mechanism for AGE toxicity.
- Significant challenges exist in standardizing AGE detection and measurement.
Conclusions:
- AGEs play a significant role in the pathogenesis of diabetic complications.
- Further research is needed to clarify the causal relationship between AGEs and complications.
- Development of standardized detection methods and effective therapeutic agents is crucial.