Endocrine Abstracts

Introduction: Bariatric surgery is an effective therapy for patients with type 2 diabetes mellitus (T2D). Many mechanisms have been proposed for its metabolic benefits, such as caloric restriction, weight loss, increased secretion of gut hormones like glucagon-like peptide 1 (GLP-1) and 2 (GLP-2), bile acid diversion, decrease of pancreatic and hepatic fat deposits and changes in gut microbiome.

Aims: Evaluate changes after surgery in gut microbiome profile, incretin secretion, intestinal permeability, systemic inflammation and succinate levels. Assess the associations between former variables and determine predictors of metabolic outcomes.

Material and Methods: Prospective single-center, non-blinded randomized controlled trial study, including patients with grades II and III obesity and T2D undergoing metabolic RYGB (mRYGB). At baseline and at one year after surgery we performed anthropometric, body composition, biochemical analysis including fasting IL-6 and zonulin, a standard meal test (SMT) and lipid test (LT) with plasma insulin, C-peptide, plasma GLP-1, GLP-2, succinate, and the study of gut microbiota was performed.

Results: 13 patients were evaluated, 9 females and 4 males, mean age 52.6±6.5 years, mean BMI 39.3±1.4 kg/m², initial HbA1c of 7.62±1.5% with 69.2% under insulin treatment. Twelve months after surgery a reduction of 33% of total weight loss at the expense of fat mass was observed. Diabetes remission was achieved in 69% of patients. Fasting plasma succinate and zonulin significantly decreased after surgery. After SMT and LT a significant increase in AUC for GLP-1 and GLP-2 and C- peptide was observed after surgery whereas AUC for glucose significantly decreased. Patients achieving T2D remission had higher initial C-peptide but similar proportion of insulin treatment and incretin response. In the multiple regression analysis only higher initial C-peptide levels predicted better metabolic outcomes. The microbiota analysis showed a significant increase in beta diversity after surgery. Compared to pre-surgical faeces samples, certain families increased after mRYGB including Veillonellaceae, Enterobacteriaceae, Streptococaceae and Prevotellaceae, and were negatively correlated with HbA1c and BMI. On the contrary, some families significantly decreased: Eubacteriaceae, Ruminococcaceae, Clostridiaceae and Erysipelotrichaceae, and showed an inverse correlation with former parameters. Therefore, those families increasing after surgery were associated with a better metabolic profile. No association was found between microbiota families and incretin profile or gut permeability markers.

Conclusions: We showed beneficial changes in multiple aspects following mRYGB, spanning from an enhanced incretin secretion, decreased intestinal permeability and succinate levels to a shift towards a specific healthier metabolic microbiome.