Metabolic syndrome is a medical condition characterized by central obesity, elevated triglycerides, small low-density lipoprotein (LDL) particles, low beneficial high-density lipoprotein (HDL) cholesterol, elevated blood pressure, increased inflammation, and insulin resistance. AGE accumulation and RAGE expression is correlated with the symptoms of this condition. A variant of RAGE known as endogenous secretory RAGE (esRAGE) is believed to be a decoy receptor for AGEs and increased levels of esRAGE have been shown to be protective in atherosclerosis and metabolic syndrome. Additionally, esRAGE levels are inversely correlated with body mass index, blood pressure, insulin resistance, and triglycerides.13 (See Chapter 24 on metabolic syndrome.)
AGEs are not the only cause of pathology related to diabetes. Glucotoxicity and lipotoxicity are important factors in the development and progression of diabetes. For example, hyperglycemia induces oxidative stress, which causes significant damage to proteins and lipids.14 Also, intracellular lipid accumulation disrupts kinases and other intracellular signaling pathways, leading to chronic inflammation. Furthermore, hyperglycemia has several pathological consequences, such as atherogenic dyslipidemia and endothelial dysfunction.15
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