Reza Nemati1, Jun Lu2,3,4,5, Dech Dokpuang1,6, Michael Booth7, Lindsay D Plank8, Rinki Murphy9,10,11,12. 1. School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. 2. School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Private Bag 92006, Auckland, 1142, New Zealand. jun.lu@aut.ac.nz. 3. College of Life and Marine Sciences, Shenzhen University, Shenzhen, Guangdong Province, China. jun.lu@aut.ac.nz. 4. School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand. jun.lu@aut.ac.nz. 5. Institute of Biomedical Technology, Auckland University of Technology, Auckland, New Zealand. jun.lu@aut.ac.nz. 6. Division of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao, Thailand. 7. Department of Surgery, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand. 8. Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. 9. Auckland Diabetes Centre, Auckland District Health Board, Auckland, New Zealand. r.murphy@auckland.ac.nz. 10. Whitiora Diabetes Department, Counties Manukau District Health Board, Auckland, New Zealand. r.murphy@auckland.ac.nz. 11. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. r.murphy@auckland.ac.nz. 12. Maurice Wilkins Centre for Biodiscovery, Auckland, New Zealand. r.murphy@auckland.ac.nz.
Abstract
BACKGROUND:Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF19) to such metabolic improvements is unclear. METHODS: We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obese patients with T2DM before and 1 year after randomization to SG or RYGB. RESULTS:Weight loss and diabetes remission (defined by HbA1c < 39 mmol/mol [< 5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss - 29 vs - 31 kg, p = 0.50; diabetes remission proportion 37.5 vs 34%, p = 1.0). Greater increments in fasting and prandial levels of total, secondary, and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r = - 0.3, p = 0.01; r = - 0.2, p = 0.04), secondary (r = - 0.3, p = 0.01; r = - 0.4, p = 0.01) and unconjugated BA (r = - 0.3, p = 0.01; r = 0.4, p < 0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r = 0.2, p = 0.03), HbA1c (r = 0.3, p = 0.01), and negatively associated with changes in insulinogenc index (r = - 0.3, p = 0.01). Only changes in prandial FGF19 were negatively associated with HbA1c (r = - 0.4, p < 0.01) and visceral fat (r = - 0.3, p = 0.04). CONCLUSIONS/ INTERPRETATION: The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.
RCT Entities:
BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF19) to such metabolic improvements is unclear. METHODS: We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obesepatients with T2DM before and 1 year after randomization to SG or RYGB. RESULTS:Weight loss and diabetes remission (defined by HbA1c < 39 mmol/mol [< 5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss - 29 vs - 31 kg, p = 0.50; diabetes remission proportion 37.5 vs 34%, p = 1.0). Greater increments in fasting and prandial levels of total, secondary, and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r = - 0.3, p = 0.01; r = - 0.2, p = 0.04), secondary (r = - 0.3, p = 0.01; r = - 0.4, p = 0.01) and unconjugated BA (r = - 0.3, p = 0.01; r = 0.4, p < 0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r = 0.2, p = 0.03), HbA1c (r = 0.3, p = 0.01), and negatively associated with changes in insulinogenc index (r = - 0.3, p = 0.01). Only changes in prandial FGF19 were negatively associated with HbA1c (r = - 0.4, p < 0.01) and visceral fat (r = - 0.3, p = 0.04). CONCLUSIONS/ INTERPRETATION: The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.
Entities:
Keywords:
Bariatric surgery; Bile acids; Energy expenditure; HbA1c; Roux-en-Y gastric bypass; Sleeve gastrectomy
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