a-00121 Dr. Robert RUTLEDGE Title of Paper: BILE ACID DEPLETION WITH GASTRO-INTESTINAL BYPASS DECREASES HGB-A1C & SERUM GLUCOSE AND IMPROVES INSULIN SENSITIVITY. Nationality: United States of America Position: Director Department: SurgeryOrganization: Center For Laparoscopic Obesity Surgery Tel: +1-702 714 0011 E-mail: firstname.lastname@example.org
BILE ACID DEPLETION WITH GASTRO-INTESTINAL BYPASS DECREASES HGB-A1C & SERUM GLUCOSE ANDIMPROVES INSULIN SENSITIVITY Robert RUTLEDGE11Director, Surgery, Center For Laparoscopic Obesity Surgery, United States of America
Introduction• Long term studies show deterioration of the initial improvement in diabetes after bariatric surgery over time.• New research shows that Bile Acids (BAs) are signaling molecules, with systemic endocrine functions.• Decrease in BAs can decrease fat absorption, triglyceride, cholesterol, energy, and• HORMONALLY ACT improve glucose homeostasis.
Bile Acid BindingColesevelam a bile acid sequestrantManipulation of the bile acid pool plays a role in glucose homeostasis
Bile acid Sequestrants reduceglucose levels in patients with type 2 diabetes mellitus
Farnesoid X receptor (FXR)• The bile acid receptor (BAR), also known as Farnesoid X receptor (FXR) is a nuclear receptor• FXR is expressed at high levels in the liver and intestine.• FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes
• The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity.
Bile Acids & FXR• Decrease in Bile Acids Decreases FXR attenuates body weight gain and reduces adipose tissue mass in animal and human models.• Glucose homeostasis is improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity.• Decreasing elevated plasma BA concentrations in obese mice by administration of the BA sequestrant colesevelam improved glucose homeostasis in a FXR-dependent manner,
Bile acids and signal transduction: Role in glucose homeostasis• Regulation of glucose metabolism by bile acids• Regulates Farnesoid X receptor (FXR), which can stimulate the insulin receptor (IR)
Methods:• Reviewed literature on• Bile Acids as critical factors in• Glucose homeostasis and• Recent publications on• Bile Acid Pool manipulation in the• Management of Diabetes.
Methods• Review of data showing that duodenal bypass as part of• Combined Gastro-Intestinal Procedures (CGIPs) decrease BA pool (Shorter Bowel)• decreasing weight, lipids,• Hormonal Effect: improves insulin sensitivity and glucose homeostasis• Further support to the importance to the bypass component of durable weight loss procedures.
Results• Bile acids are known to facilitate digestion and absorption of lipids and regulate cholesterol homeostasis.• It has now become clear that bile acids are critical hormones involved in activation of various signaling pathways, including triglyceride, cholesterol, glucose, and energy homeostasis.
Results• Studies show• Decrease in the bile acid pool• Results in decreases in hemoglobin A1c, glucose levels and• Improved insulin sensitivity.
Results• Recent studies from Korea and China have shown that in comparison to• Primary Gastric Procedures (PGP) the use• Combined Gastro-Intestinal Procedures (CGIP) improve the success in the resolution of diabetes.• Combined procedures include duodenal bypass which leads to decrease in bile acid pool.
Conclusions:• Bile acids regulate triglyceride, cholesterol, glucose, and energy homeostasis. (OLD)• Decreased Bile acid pool size decreases fat absorption, cholesterol and triglycerides. (OLD)
Conclusions• Bile Acids are also Gut Hormones (New)• Decreaseing Bile Acids (through modulation of FXR and TGR5)• Improves Glucose Homeostasis (New)• Manipulation of Bile Acids Hormonally can be treatment of Diabetes (New, Welchol)
Conclusions• In addition to these lipid effects• Duodenal bypass in CGIPs decreases BA pool size which leads to improved glucose homeostasis and thus• Helps explain the improved success and durability of combined bariatric procedures in comparison to primary gastric procedures (band & sleeve)