Circulating Soluble Receptor for Advanced Glycation End Products Is Inversely Associated with Glycemic Control and S100A12 Protein

Context: The interaction of advanced glycation end products, including Nε-(carboxymethyl)lysine-protein adducts (CML) and S100A12 protein, with their cellular receptor (RAGE) is implicated in the pathogenesis of diabetic vascular complications. RAGE has a circulating secretory receptor form, soluble...

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Published in:The journal of clinical endocrinology and metabolism 2006-11, Vol.91 (11), p.4628-4634
Main Authors: Basta, Giuseppina, Sironi, Anna Maria, Lazzerini, Guido, Del Turco, Serena, Buzzigoli, Emma, Casolaro, Arturo, Natali, Andrea, Ferrannini, Ele, Gastaldelli, Amalia
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Blood Glucose - analysis
Blood Pressure
C-Reactive Protein - analysis
Case-Control Studies
Diabetes Mellitus, Type 2 - blood
Diabetic Angiopathies - blood
Diabetic Angiopathies - epidemiology
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Glycated Hemoglobin A - analysis
Glycation End Products, Advanced - blood
Glycation End Products, Advanced - metabolism
Humans
Inflammation Mediators - blood
Lysine - analogs & derivatives
Lysine - blood
Male
Medical sciences
Middle Aged
Receptor for Advanced Glycation End Products
Receptors, Immunologic - blood
Risk Factors
S100 Proteins - blood
S100A12 Protein
Statistics as Topic
Vertebrates: endocrinology
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Summary:Context: The interaction of advanced glycation end products, including Nε-(carboxymethyl)lysine-protein adducts (CML) and S100A12 protein, with their cellular receptor (RAGE) is implicated in the pathogenesis of diabetic vascular complications. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which, by neutralizing the action of advanced glycation end products, might exert a protective role against the development of cardiovascular disease. Objective: The objective of the study was to investigate whether plasma sRAGE levels are associated with glycemic control, proinflammatory factors, or circulating ligands of RAGE such as plasma CML and S100A12 protein. Study Design: We studied 160 subjects, 84 subjects with type 2 diabetes (aged 60 ± 7 yr) and 76 nondiabetic controls (aged 45 ± 10 yr). Results: Plasma sRAGE was lower in diabetic patients than controls [141 (53–345) vs. 735 (519–1001) pg/ml, median (interquartile range), P < 0.0001], whereas CML levels were higher in diabetic patients than controls [67.9 (46.0–84.7) vs. 43.4 (28.0–65.0) μg/ml, P < 0.0001]. In stepwise regression analysis of the whole data set, hemoglobin A1c, insulin resistance (as homeostasis model assessment), and C-reactive protein were independently associated with plasma sRAGE, whereas age was not. In a subgroup of 26 diabetic and 24 nondiabetic subjects of similar age (54 ± 3 yr), plasma S100A12 levels were higher in diabetic subjects [49 (39–126) vs. 28 (21–39) ng/ml]. Moreover, low sRAGE and high S100A12 were strongly associated with increased risk for cardiovascular disease (Framingham score). In this subgroup, the plasma S100A12 level was the only determinant of plasma sRAGE concentration. Conclusion: Plasma level of sRAGE is down-regulated in chronic hyperglycemia; among its ligands, S100A12 protein, but not CML, appears to be associated with this effect.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2005-2559