the surgical: proximal and distal intestine, partial removal of the stomach, ileal transposition,...
TRANSCRIPT
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 Unitwww.metabolicsurgeryistanbul.com
1st Question?
• Did initial vertebrates have an appendix epiploica?
Herbivore Carnivore
Gastrointestinal adaptation to fiber-poor diets
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
DuodenojejunalHyperactivity
High GIP
Ileal Hypoactivity
Low PYY, GLP-1 and OXM
A Proximal – Distal Imbalance
By bringing the ileum proximal
We will obtain an Adaptive andNeuroendocrine support
How about pathophysiology?
TRIUNVIRATO1. 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)
Diabetes 2009:58; 773-95.
Steps for Success in Metabolic Surgery1) 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 resistance7) 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)
12
0,00
100,00
200,00
300,00
400,00
500,00
600,00
700,00Ghrelin
Pre-op 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
LiverLiver / / MuscleMuscle AdipoAdipocycyttee
Insulin
GIP – trivial effect
FatFat
GIP & Decreased insulin
Fat
LiverLiver / / MuscleMuscle
AdipoAdipocycyttee
Decreased insulin activity
GIP – effective
GIP & Corrected Insulin
Fat
LiverLiver / / MuscleMuscle
AdipoAdipocycyttee
Corrected insulin activity
GIP – inhibition
“Vicious Cycle” of GIP Molecule
Hyperphagia K-cell hyperplasia
GIP Increased
Beta-cell hyperplasia
Insulin Resistance
Hyperinsulinemia
Hyperglycemia
Glucose Intolerance
Beta-cell stimulation
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.
p<0.001 - preoperative vs postoperativea p<0.05 - 1-12months vs 25-38 months
* * *
**
Time Based Evaluation (3 years) of Insulin Sensitivity After II-SG in T2DM Patients with BMI<35
Vencio S. Endocrine Reviews 2010;31(3):S1-257
*a
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 SwitchBPD + Duodenal Switch
Bypassed duodenum Bypassed duodenum and jejunum for a and jejunum for a Malabsorptive Malabsorptive componentcomponent
Neuroendocrine Neuroendocrine componentcomponentby enhancing entero-by enhancing entero-hormoneshormones
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
IntentionalNeuroendocrine component
Easier and saferanastomosis
NO excluded segmentTOTAL endoscopic accessNO 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”
80 to 130cm
Shorter Common segment“More bariatric procedure”Longer common segment“More metabolic procedure”
L cells of distal gut are
very close anyway
Transit Bipartition
PylorusPylorusGastro-ileal AnastomosisGastro-ileal Anastomosis
And the second option could be: DS-II
Sleeve resection/ Gastric fundectomy
Duodenal Transection
Ileo – Jejunal Interposition
-cell glucose sensitivity
* p<0.001 vs corresponding group before surgery
0
10
20
30
40
50
60
70
pre post
ß-G
S p
mol
/min
/m2/
mM
)
lean OW OB pre
*
*
*
Mechanisms of action in insulin sensitivity and beta cell functions after II-SG
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
*p<0.001 – preoperatif vs postoperatif
Vencio S et al.- Diabetes 2010;59:S1
26
Insulin Sensitivity
50
150
250
350
450
pre post
OG
IS -m
l/m
in/m
2
lean OW OB
* *
*
* p<0.001 vs corresponding group before surgery
Increase in Insulin Sensitivity According to BMI Values
DePaula AL, Ferranninni E, et al. – J Gastrointest Surg 2011;15(8):1344-1353
Without long term Nutritional Effects