1. 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: Surgery
Organization: Center For Laparoscopic Obesity Surgery
Tel: +1-702 714 0011
E-mail: drr@clos.net

2. BILE ACID DEPLETION
WITH
GASTRO-INTESTINAL BYPASS
DECREASES HGB-A1C &
SERUM GLUCOSE AND
IMPROVES INSULIN SENSITIVITY
Robert RUTLEDGE1
1Director, Surgery, Center For Laparoscopic
Obesity Surgery, United States of America

3. 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.

4. Bile Acid Binding
Colesevelam a bile acid sequestrant
Manipulation of the bile acid pool plays a role in glucose homeostasis

5. Bile acid Sequestrants reduce
glucose levels in patients with
type 2 diabetes mellitus

6. 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

7. • The nuclear BA receptor farnesoid X
receptor (FXR) regulates pathways in BA,
lipid, glucose, and energy metabolism,
which become dysregulated in obesity.

8. 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,

9. 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)

11. 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.

12. 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.

13. 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.

14. Results
• Studies show
• Decrease in the bile acid pool
• Results in decreases in
hemoglobin A1c, glucose levels
and
• Improved insulin sensitivity.

18. 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.

19. Conclusions:
• Bile acids regulate
triglyceride, cholesterol, glucose, and
energy homeostasis. (OLD)
• Decreased Bile acid pool size decreases
fat absorption, cholesterol and
triglycerides. (OLD)

20. 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)

21. 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)