OBJECTIVE:The increased cardiovascular (CV) disease risk in patients with morbid obesity (MO) cannot be fully explained by traditional CV risk factors. Activation of the receptor of Advanced Glycation Endproducts (RAGE) leads to inflammation via the NF kb (nuclear factor kb) pathway. The soluble form of RAGE (sRAGE), which is present in plasma, can bind to ligands of RAGE and avoids interaction of RAGE with proinflammatory ligands. We investigated sRAGE levels in patients with MO and compared them with healthy lean controls (CO), before and after bariatric surgery. DESIGN: We conducted a cross-sectional study and a 24-month longitudinal study. SUBJECTS: We included 85 patients (mean age: 41±12 years; mean body mass index (BMI): 45.4±7.9 kg m À 2 ) with MO in comparison with 40 CO (mean age: 42 ± 13 years; mean BMI: 26.0 ± 5.5 kg m À 2 ). All patients were investigated before and 2 years after bariatric surgery. Apart from weight and CV risk markers (blood pressure, lipids), a glucose tolerance test (75 g), renal and inflammation parameters were assessed. sRAGE levels were assessed by a commercial ELISA. To investigate the associations of the observed reductions of values, delta (D) of parameters were calculated. RESULTS: Patients with MO had significant lower sRAGE levels than CO: 1010 ± 514 vs 1501 ± 674 pg ml À 1 ; Po0.001. In the longitudinal study, sRAGE levels increased significantly after bariatric surgery from 1010±514 to 1261±710 pg ml À 1 ; P ¼ 0.008. In the correlation analysis, DsRAGE levels were associated with D1-h and D2-h postprandial glucose, Dfasting insulin, D2-h postprandial insulin, DHOMA (homeostatic model assessment)-insulin resistance (DHOMA-IR), Dg-glutamyl transferase and Dtriglycerides. In a multivariate model, D1-h and D2-h postprandial glucose, D2-h postprandial insulin and DHOMA-IR predicted DsRAGE. CONCLUSION: Patients with MO have significantly lower sRAGE levels compared with non-obese CO, but sRAGE levels increase significantly after weight loss induced by bariatric surgery. As high sRAGE levels inhibit the activation of inflammatory pathways, our results might help understand the beneficial effects of bariatric surgery regarding CV morbidity and mortality. Keywords: morbid obesity; sRAGE; insulin resistance; prospective INTRODUCTION Hyperglycemia leads to non-enzymatic glycation of intracellular and extracellular protein by forming advanced glycation endproducts (AGEs). 1 The RAGE (receptor of AGEs), a multi-ligand member of the immunoglobulin superfamily of transmembrane cell surface molecules, is a specific membrane-bound receptor for AGEs, 2 and activation of the RAGE by AGEs has a major role in the pathogenesis of diabetic vascular complications by way of activation of the NF kb (nuclear factor kb) pathway. 3 sRAGE is the soluble receptor of RAGE existing in the circulation. sRAGE levels have been found to be associated with chronic inflammatory diseases, including atherosclerosis and diabetes. 4-6 sRAGE acts as a decoy to prevent an interaction between AGE and RAGE and ther...

We could demonstrate a significant decrease in MV-TF activity after weight loss in morbidly obese patients. Decreased MV-TF activity might contribute to an improved coagulation profile in these patients after weight loss.

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