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AE Pontiroli, P Pizzocri, D Koprivec, P Vedani, M Marchi, C Arcelloni, R Paroni, K Esposito, and D Giugliano

BACKGROUND: Endothelial dysfunction and inflammation are present in both type 2 diabetes mellitus (T2DM) and obesity. In this paper we compared the role of weight loss and of glycaemic control in determining circulating levels of ICAM-1, endothelin-1 (ET-1), and E-selectin in patients with morbid (grade 3) obesity. METHODS AND RESULTS: ICAM-1, E-selectin, and ET-1 were higher in obese patients (n=96) than in lean controls (n=30); among obese patients, the three molecules were higher in T2DM patients (n=26) than in patients with normal (NGT, n=43) or impaired (IGT, n=27) glucose tolerance. Sixty-eight obese patients had a significant weight loss induced by bariatric surgery, and showed a significant decrease in blood glucose, HbA1c and all molecules, so that ICAM-1, E-selectin, and ET-1 were not different in NGT, IGT and T2DM patients, and in lean controls; in 13 patients with a small weight loss induced by diet, changes were not significant, in spite of a significant reduction in blood glucose and HbA1c. At stepwise regression, changes in ICAM-1, ET-1, and E-selectin significantly correlated only with change in body mass index. CONCLUSIONS: These data indicate that weight loss is more important than glycaemic control in regulating circulating levels of ICAM-1, ET-1, E-selectin in morbidly obese subjects.

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E Setola, LD Monti, E Galluccio, A Palloshi, G Fragasso, R Paroni, F Magni, EP Sandoli, P Lucotti, S Costa, I Fermo, M Galli-Kienle, A Origgi, A Margonato, and P Piatti

OBJECTIVE: The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. DESIGN AND METHODS: A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month. RESULTS: In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables. CONCLUSIONS: Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors.