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