The Surgical: proximal and distal intestine,
partial removal of the
stomach, ileal transposition, others
Alper Çelik, M.D.
Associate Professor of Surgery
Yeni Yüzyıl University Medical Faculty
& Taksim German Hospital
Metabolic Surgery Unit
www.metabolicsurgeryistanbul.com
1st Question?
• Did initial vertebrates have an appendix
epiploica?
Gastrointestinal adaptation to fiber-poor diets
Herbivore
Carnivore
Who consumes the diet
with higher caloric index?
The goat has a bigger stomach that
than the dog’s stomach.
And longer intestines also.
the dog is not restricted.
The dog is adapted!
Is Sleeve gastrectomy a restrictive or adaptive procedure?
Reflections o the concept of Restriction and Adaptation.
Change in Food Industry
•
•
•
•
Refined food
Saccharification
Coca-colanisation!!!
And their metabolic outcomes.
Obesity and Metabolic Syndrome
A Proximal – Distal
Imbalance
Duodenojejunal
Hyperactivity
High GIP
Ileal Hypoactivity
Low PYY, GLP-1 and OXM
By bringing the ileum proximal
We will obtain an Adaptive and
Neuroendocrine support
How about pathophysiology?
Diabetes 2009:58; 773-95.
TRIUNVIRATO
1. Inadequate insulin release
from beta cells, disrupted
early phase insulin effect
2. Insulin Resistance (IR) in
peripheral tissues
3. Increased endogenous
glucose production (hepatic /
intestinal glucose output)
4. Adipocytes
OCTETO
5. Gastrointestinal tractus
(incretin insufficiency /
resistance)
6. Alpha cell (hyperglucagonemia)
7. Kidney (glucose reabsorption)
8. CNS (insulin resistance - others)
Steps for Success in Metabolic Surgery
1) Caloric restriction and weight adjustments based on “hormonal
thermostat” mechanism.
2) Increased gastric emptying and decreased ghrelin levels
3) Early term food contact with the ileal mucosa, increase in GLP-1 and
correction of the first phase insulin release (“jejuno ileal nutrient
sensing”)
4) Correction of first + second phase (20-120 min) glucose dependent
plasma insulin response due to GIP effect
5) Correction of late phase inadequate glucagon supression
6) Decrease in Hepatic and peripheral insulin resistance
7) Decrease in Hepatic Glucose Output
• *Breen DM, et al. Nature Med 2012; 18: 950-955.
1) Caloric Restriction
Sleeve Gastrectomy
causes
functional restriction
and
endocrine adjustments
2) Increased gastric emptying and
decreased ghrelin levels
It reduces Ghrelin
(Now we know it also
enhances GLP1 and PYY)
700,00
Ghrelin
600,00
500,00
400,00
300,00
200,00
100,00
0,00
1
Pre-op
2
Post-op
What is Ghrelin?
• Hormone?
GHRELIN
• Growth Hormone Receptor Ligand
• Ghrelin deficiency may not be innocent!
• Keep an eye on Journal of Bone & Mineral
Research!
3-4-5) Incretin Effect & Glucagon
Supression
• In patients with T2DM insulin release and beta
cell functions are altered.
• Insulin has a biphasic release pattern from
pancreas.
• Early phase occuring within first 30 min
• Late phase that platoes after 2nd hour
• The earliest possible sign of beta cell
dysfunction is the disrupted early phase
insulin release.
Kahn SE Int J Clin Pract 2001;123:13-18
Early Phase Insulin Release -1
• If early phase insulin release is disrupted;
1 – Insulin sensitive tissues fail to adequately
perform glucose transport.
2 – Glucagon secretion, FFA release and Hepatic
Glycogenolysis can not be prevented.
3 – Circulating glucose load and glycemic
variability will increase.
Luzi L et al Am J Physiol 1989;257:E241-E246
Early Phase Insulin Release -2
• The reason for these changes is intrinsic beta cell
defect + Defective changes in factors promoting
postprandial insulin secretion (Incretin Resistance &
Insufficiency).
• There are two forms of basic physiologically active
incretins (Intestinal İnsulinomimetic Polipeptides):
• GIP and GLP-1.
GIP (Glucose-Dependent
Insulinotropic Polypeptide )
• Is GIP a good hormone or a bad hormone?
GIP
• The answer is “both” (depending on the situation).
• It is mainly released from the K cells in the duodenum.
• Especially in pts with IGT its levels increase in parallel to
hyperinsulinemia. Oral glucose load exeggerates this
increase.
RESULT:
• K cell desensitisation to oral glucose
• GIP receptor desensitisation
• Beta cell GIP Resistance
Theodorakis MJ, et al Diabetes Care 2004; 27: 1692-98.
GIP & Trivial Pattern
GIP – trivial effect
Liver / Muscle
Fat
Insulin
Adipocyte
GIP & Decreased insulin
GIP – effective
Fat
Liver / Muscle
Decreased insulin activity
Adipocyte
GIP & Corrected Insulin
GIP – inhibition
Fat
Liver / Muscle
Corrected insulin activity
Adipocyte
“Vicious Cycle” of GIP Molecule
Hyperphagia
K-cell hyperplasia
GIP Increased
Beta-cell hyperplasia
Beta-cell stimulation
Hyperinsulinemia
Insulin Resistance
Hyperglycemia
Glucose Intolerance
Gault, VA et al (2005). Diabetes 54:2436-2446.
GLP-1 (Glucagon Like Peptide 1)
• It is mainly released from L cells in Ileum.
• It leads to Receptive Partial Antagonism with
Glucagon (“dysinhibition”).
• GLP-1 shows a secretion kinetic based on the
oligosaccharides within ileum and is the main
factor in adjusting early phase insulin release.
• GLP-1 secretion is altered in T2DM.
Time Based Evaluation (3 years) of Insulin Sensitivity
After II-SG in T2DM Patients with BMI<35
Hepatic Resistance Index
233
*
200
183
*
182
0.12
*
184
150
100
50
0.1
0.1
Dg/dt÷I
glic0-30AUC X ins0-30AUC.10-6
250
Muscular Sensitivity
*
Index*
0.08
*
a
0.11 0.11
0.08
0.06
0.04
0.02
0
0
Pre
1-12 13-24 25-38
Vencio S. Endocrine Reviews 2010;31(3):S1-257
Pre 1-12 13-24 25-38
p<0.001 - preoperative vs postoperative
a p<0.05 - 1-12months vs 25-38 months
Surgical Success – Things To Do!
• Sleeve gastrectomy
• Correction of disrupted GIP secretion (Duodenal
Exclusion)
• GLP-1 effect (ileal proximalisation)
• Glucagon Suppression
• Decrease in hepatic glucose output
• Without long term malapsorption.
BPD + Duodenal Switch
Neuroendocrine component
by enhancing enterohormones
Bypassed duodenum and
jejunum for a
Malabsorptive component
Is the answer BPD/DS?
• If we want to end one form of addiction and
give our patients a new form of addiction
(vitamins, minerals, calcium, iron, and trace
elements); than the answer is YES.
One possible option: transit bipartition
Intentional
Neuroendocrine
component
Easier and safer
anastomosis
NO excluded segment
TOTAL endoscopic access
NO Nutritional problems
Santoro et al.
Obes Surg 2006; 16:1371-79
Obes Surg 2008; 18:1343–1345
Ann Surg. 2012 Jul;256(1):104-10.
Bipartition
Gastroileoanastomosis
240 to 260 cm
from the cecum
A very flexible procedure
A Smaller gastric remnant
“More bariatric procedure”
A Bigger remnant
“More metabolic procedure”
L cells of
distal gut are
very close
anyway
Shorter Common segment
“More bariatric procedure”
Longer common segment
“More metabolic procedure”
80 to 130cm
Transit Bipartition
Gastro-ileal Anastomosis
Pylorus
And the second option could be: DS-II
Sleeve resection/
Gastric fundectomy
Duodenal
Transection
Ileo – Jejunal
Interposition
Mechanisms of action in insulin sensitivity
and beta cell functions after II-SG
-cell glucose sensitivity
ß-GS pmol/min/m2/mM)
70
60
*
50
*
*
40
30
20
10
0
pre
lean
post
OW
OB pre
* p<0.001 vs corresponding group before surgery
DePaula AL, Ferranninni E, et al. – J Gastrointest Surg 2011;15(8):1344-1353
Evaluation of Insulin Sensitivity and Secretion by
Eauglycemic Hyperinsulinemic Clamp + IVGTT
in patients with BMI<35
Glucose dependent C-peptide release
AUC C-peptide/AUC glucose
30
AUC C-peptid / AUC glukoz
*
27.4
25
20
15
10
10.2
5
0
Preoperative
Postoperative
*p<0.001 – preoperatif vs postoperatif
Vencio S et al.- Diabetes 2010;59:S1
26
Increase in Insulin Sensitivity According to BMI Values
Insulin Sensitivity
OGIS - ml/min/m2
450
*
*
*
350
250
150
50
pre
post
lean
OW
OB
* p<0.001 vs corresponding group before surgery
DePaula AL, Ferranninni E, et al. – J Gastrointest Surg 2011;15(8):1344-1353
Without long term Nutritional Effects