Abstract
Metabolic syndrome (MetS) is considered one of the most important public health problems. Several and controversial studies showed that the role of advanced glycation end products (AGEs) and their receptor in the development of metabolic syndrome and therapeutic pathways is still unsolved. We have investigated whether plasma pentosidine, carboxymethyl-lysine (CML), and soluble receptor for advanced glycation end products (sRAGE) levels were increased in patients with MetS and the effect of metformin in plasma levels of pentosidine, CML, and sRAGE. 80 control subjects and 86 patients were included in this study. Pentosidine, CML, and sRAGE were measured in plasma by enzyme-linked immunosorbent assay (ELISA). Plasma pentosidine, CML, and sRAGE levels were significantly increased in patients compared to control subjects (P < 0.001, P < 0.001, and P = 0.014, resp.). Plasma levels of pentosidine were significantly decreased in patients who received metformin compared to untreated patients (P = 0.01). However, there was no significant difference between patients treated with metformin and untreated patients in plasma CML levels. Plasma levels of sRAGE were significantly increased in patients who received metformin and ACE inhibitors (P < 0.001 and P = 0.002, resp.). However, in a multiple stepwise regression analysis, pentosidine, sRAGE, and drugs treatments were not independently associated. Patients with metabolic syndrome showed increased levels of AGEs such as pentosidine and CML. Metformin treatment showed a decreased level of pentosidine but not of CML. Therapeutic pathways of AGEs development should be taken into account and further experimental and in vitro studies merit for advanced research.
Highlights
Cardiovascular diseases are one of the main causes of mortality in industrialized countries, due to an increase in prevalence of different cardiovascular risk such as abdominal obesity, insulin resistance, dyslipidemia, hypertension, and hyperglycemia
Due to complex metabolic disorder in metabolic syndrome, reactive derivatives are formed via nonenzymatic reaction named Maillard reaction between the free amino groups in lysine and arginine residues in proteins and carbohydrates that undergo a series of complex reactions to an irreversible complex group of compound termed advanced glycation end products (AGEs) [2, 3]
Patients were divided into patients who are treated with metformin (Glucophage 850 mg; 3 times/day) (n = 55) and patients who are untreated with this drug (n = 31)
Summary
Cardiovascular diseases are one of the main causes of mortality in industrialized countries, due to an increase in prevalence of different cardiovascular risk such as abdominal obesity, insulin resistance, dyslipidemia, hypertension, and hyperglycemia. Due to complex metabolic disorder in metabolic syndrome, reactive derivatives are formed via nonenzymatic reaction named Maillard reaction between the free amino groups in lysine and arginine residues in proteins and carbohydrates that undergo a series of complex reactions to an irreversible complex group of compound termed advanced glycation end products (AGEs) [2, 3]. These products can be formed by covalent binding of methylglyoxal (MG) and glyoxal to the free amino and thiol groups of proteins [4]
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