Abstract
Advanced glycation end-products (AGEs) generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE)), were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE). TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD) and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyl)lysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD.
Highlights
Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century.Increases are reported each year in the number of individuals with this hyperglycemic condition, which may result in life-changing complications
We evaluated the amounts of various advanced glycation end-products (AGEs) in 885 kinds of daily sugar intake recommended in the guidelines by the American Heart Association (AHA) [130] and World Health Organization (WHO) [131] to prevent health beverages and 767 kinds of food, and found that the amounts of AGEs derived from Glu-AGEs/Fruconditions in women and adults/children, respectively
Changes in serum toxic AGEs (TAGE) levels are closely associated with metabolic syndrome (MetS) and insulin resistance (IR), postprandial hyperglycemia, dyslipidemia, and hypertension, which are related to overeating, the lack of exercise, or excessive ingestion of sugars (HFCS and sucrose)/dietary AGEs (Figure 2)
Summary
Diabetes mellitus (DM) is one of the largest global health emergencies of the 21st century. AGEs are generated by the Maillard reaction, a non-enzymatic reaction, between the aldehyde or ketone groups of reducing sugars, such as glucose and fructose, and the N-terminal α-amino group or ε-amino group of the lysine residues of proteins, and contribute to the aging of proteins as well as pathological complications associated with DM [2,3,4,5,6,7,8,9] In hyperglycemia, this process begins with the conversion of reversible Schiff base adducts to more stable, covalently bound Amadori rearrangement products. The structures of cytotoxic AGEs have not yet been elucidated
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