R Dutia1, M Embrey1, C S O'Brien, S O'Brien1, R A Haeusler2, K K Agénor1, P Homel3, J McGinty4, R P Vincent5, J Alaghband-Zadeh6, B Staels7, C W le Roux8, J Yu1, B Laferrère1. 1. New York Obesity Nutrition Research Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. 2. Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, USA. 3. Department of Medicine, Albert Einstein School of Medicine, New York, NY, USA. 4. Division of Bariatric and Minimally Invasive Surgery, Department of Surgery, Mount Sinai, St. Luke's Roosevelt Hospitals, New York, NY, USA. 5. Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust Denmark Hill, London, UK. 6. Department of Clinical Biochemistry, Guy's & St Thomas' NHS Foundation Trust, London, UK. 7. European Genomic Institute for Diabetes (EGID), Université Lille 2, Inserm UMR 1011, Institut Pasteur de Lille, Lille, France. 8. Diabetes Complications Research Center, Conway Institute, University College, Dublin, Ireland.
Abstract
INTRODUCTION: Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM. METHODS: Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obese women with T2DM. RESULTS: A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found. CONCLUSIONS: This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.
INTRODUCTION: Gastric bypass surgery (GBP) leads to sustained weight loss and significant improvement in type 2 diabetes (T2DM). Bile acids (BAs), signaling molecules which influence glucose metabolism, are a potential mediator for the improvement in T2DM after GBP. This study sought to investigate the effect of GBP on BA levels and composition in individuals with T2DM. METHODS: Plasma BA levels and composition and fibroblast growth factor (FGF)-19 levels were measured during fasting and in response to an oral glucose load before and at 1 month and 2 years post GBP in 13 severely obesewomen with T2DM. RESULTS: A striking temporal change in BA levels and composition was observed after GBP. During the fasted state, BA concentrations were generally reduced at 1 month, but increased 2 years post GBP. Postprandial BA levels were unchanged 1 month post GBP, but an exaggerated postprandial peak was observed 2 years after the surgery. A significant increase in the 12α-hydroxylated/non12α-hydroxylated BA ratio during fasting and postprandially at 2 years, but not 1 month, post GBP was observed. Significant correlations between BAs vs FGF-19, body weight, the incretin effect and peptide YY (PYY) were also found. CONCLUSIONS: This study provides evidence that GBP temporally modifies the concentration and composition of circulating BAs in individuals with T2DM, and suggests that BAs may be linked to the improvement in T2DM after GBP.
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