Abstract

Bariatric surgery restores glucose tolerance in many, but not all, severely obese subjects with type 2 diabetes (T2D). We aimed to evaluate the plasma protein profiles associated with the T2D remission after obesity surgery. We recruited seventeen women with severe obesity submitted to bariatric procedures, including six non-diabetic patients and eleven patients with T2D. After surgery, diabetes remitted in 7 of the 11 patients with T2D. Plasma protein profiles at baseline and 6 months after bariatric surgery were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight coupled to mass spectrometry (MALDI-TOF/TOF MS). Remission of T2D following bariatric procedures was associated with changes in alpha-1-antichymotrypsin (SERPINA 3, p < 0.05), alpha-2-macroglobulin (A2M, p < 0.005), ceruloplasmin (CP, p < 0.05), fibrinogen beta chain (FBG, p < 0.05), fibrinogen gamma chain (FGG, p < 0.05), gelsolin (GSN, p < 0.05), prothrombin (F2, p < 0.05), and serum amyloid p-component (APCS, p < 0.05). The resolution of diabetes after bariatric surgery is associated with specific changes in the plasma proteomic profiles of proteins involved in acute-phase response, fibrinolysis, platelet degranulation, and blood coagulation, providing a pathophysiological basis for the study of their potential use as biomarkers of the surgical remission of T2D in a larger series of severely obese patients.

Highlights

  • Type 2 diabetes (T2D) is common in patients with severe obesity in whom a marked weight loss frequently restores glucose tolerance [1]

  • The present study focused on the identification of the early determinants of the resolution of T2D in severely obese patients after bariatric surgery by applying a non-targeted proteomic analysis to plasma proteins

  • Our present exploratory non-targeted study identified differences in the plasma proteomic profile of diabetic patients bariatric surgery in whom diabetes Our present exploratory non-targeted study submitted identifiedto differences in the plasma persisted or remitted after weight loss, using non-diabetic but obese persons proteomic profile of diabetic patients submitted to bariatric surgery in whom diabetes as controls

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Summary

Introduction

Type 2 diabetes (T2D) is common in patients with severe obesity in whom a marked weight loss frequently restores glucose tolerance [1]. Randomized controlled trials with postoperative follow-up ranging from 1 to 5 years documented sustained diabetes remission in 30–63% of patients submitted to bariatric surgery [2,3,4], with similar remission rates regardless of specific surgical procedures [5,6]. Metabolic benefits may appear very soon after surgery, well before significant weight loss occurs [10], by mechanisms that, in addition to improvement in beta-cell function and normalization of hepatic glucose production [10,11,12], are not fully understood. The present study focused on the identification of the early determinants of the resolution of T2D in severely obese patients after bariatric surgery by applying a non-targeted proteomic analysis to plasma proteins

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