Ileal Interposition and Hormonal Mechanism of Action

Ileal Interposition surgery is a digestive system procedure which changes alignment of small intestines.  Ileal Interposition causes different metabolic changes with this new anatomy in the digestive system.   These metabolic changes provide complete normalization of Metabolic Syndrome findings including diabetes.  The actual  cause underlying all these refinements is the hormonal regulation created by Ileal Interposition surgery.
Although Ileal Interposition surgery is a digestive system procedure applied on stomach and small intestines anatomically, it may be defined as endocrine surgery in terms of its effects. All action of Ileal Interposition reviel regulation of hormonal secretion to increase insulin effect and reduce insulin resistance.

 

ILEAL INTERPOSITION: Step by Step

1. Sleeve Gastrectomy

The first step of Ileal Interposition surgery is removal of the stomach longitudinally.  This procedure is called Sleeve Gastrectomy.  Sleeve Gastrectomy procedure applied in Ileal Interposition is technically same with obesity surgery. The only and important difference is that Sleeve Gastrectomy applied for Ileal Interposition leaves a wider gastric pouch for those applied for obesity so it is weight adjusted.

The actual purpose for partial removal of stomach in Ileal Interposition surgery is to reduce hunger hormone called Ghrelin.  Ghrelin  plays a role in insulin resistance.  By reduction of Ghrelin hormone, an anti-insuliner hormone which also triggers the feeling of hunger is suppressed.

2. Duodenal Exclusion

Ileal Interposition surgery uses different mechanisms of action. This due to its wide range efficacy to use both Foregut Supression and Hindgut Stimulation.

Power of action of Ileal Interposition surgery over low BMı diabetes patients,  becomes superior than all methods known.

The Duodenal Exclusion is one of the important parts of Ileal Interposition operation.  Duodenum is separated from the stomach by Duodenal Exclusion.  So, foods can not pass into duodenum.  It is believed that separation of duodenum from foods inhibits the secretion of anti-incretin factors which increase insulin resistance.   

Furthermore, GIP (Glucose Induced Polypeptide – Gastrointestinal Polypeptide) is increased by this way.   Serum quantity of GIP hormone does not decrease in diabetic patients but functionality is spoiled.  Efficiency of GIP hormone increases in diabetic patients after duodenal exclusion procedure.  The suppression of negative incretins and GIP regulation both decreases insulin resistance and increase beta-cell activity.

 

3. Ileal Interposition

Ileal Interposition means transfer of “ileum” which is the last part of small intestines into the beginning part.  We call this re-positioning procedure as “interposition”. The actual mechanism of action of the surgery is this interposition procedure.  This procedure is performed within several stages.

i. Preparation of Ileal Segment

First, a segment from "ileum" which is the last part of small intestines is separated.  This separated part is called “ileal segment”. This ileal segment is connected to gastric exit.

ii. Ileo-Ileal Anastomosis

By removal of ileal segment, two intestinal ends which are liberated are anastomosed.  So, continuity of intestines are achieved.

iii. Duodeno-Ileal Anastomosis

The proximal tip of ileal segment is anastomosed to post-pyloric duodenal tip. This is a handsawn anastomosis. By this way, the whole gastric content is delivered directly to very distal part of ileum to stimulate GLP-1 and PYY. These two are the satiety hormones that support the insulin in all target organs to reduce the overall insulin resistance of the body.

iv. Ileo-Jejunal Anastomosis

Finally, lower end of ileal segment is connected into initiation of small intestine (40-50 cm from ligament of Treitz) and the surgery is completed. After Ileal Interposition surgery, absorption of foods from small intestines continue to be at highest level.  No malabsorption occurs.  Ileal Interposition patients absorb vitamins and minerals as normal.

ILEAL INTERPOSITION AND HORMONAL CHANGES

Ileal Interposition operation functions as an endocrine surgery.  Each procedure performed has a hormonal target and this hormonal change increases insulin efficiency.

Hormones Suppressing Insulin Effects

Hormones suppressing insulin effects are generally called as Anti-Insulinar System.  The important components of this system include Glucagon, Resistin, Ghrelin, Cortisone, Adrenalin and Nor-Adrenalin.  These hormones have periodical or permanent effects against insulin.  Levels of these hormones are analyzed before the surgery and surgery is planned.

Glucagon: It is secreted from alpha cells of pancreas.  Glucagon is secreted from cells adjacent to insulin secreting beta cells.  Glucagon’s functions are just the opposite of insulin. Glucagon  tries to increase blood glucose level.  It increases glucose production in the liver.  It reduces glucose consumption in the fat tissue and muscle.  It is primarily responsible from insulin resistance of the liver and muscle tissue.  Glucagon levels decrease after the surgery.  Stimulation of glucagon hormone to increase glucose production is eliminated by Ileal Interposition.  Furthermore, Insulin Resistance triggered by Glucagon resolves after Ileal Interposition.  These effects are on muscle and adipose tissue.

 

Resistin: Resistin hormone is another hormone causing insulin resistance.  Resistin levels especially increase by intraabdominal lipoidosis.  The site where visceral organ adiposity occurs is liver.  Liver is exposed to this lipid accumulation from onset of Type 2 diabetes.  When hepatic fat increases, fat deposits start to exist around other intra-abdominal organs and especially on posterior side of peritoneum wall (retroperitoneal area).  Resistin is secreted from this abnormal fatty deposits and primarily responsible from insulin resistance on the adipose tissue in particular.
Patients get rid of this abnormal intra-abdominal organ and tissue lipoidosis in general after Ileal Interposition operation.  By clearance of these abnormal fat deposits, Resistin levels regress to normal levels.

Resistin levels have a great importance in assessment of metabolic load of patients with Type 2 Diabetes.  Resistin hormone is high because of morbid obesity and is generally normal in slim patients.  However, the case is not always same in patients with Type 2 Diabetes.  Sometimes high Resistin levels may be detected in diabetic patients who are slightly over weighted as much as a morbid obese patent. Therefore, it is a good indicator for intra-abdominal lipoidosis rather than abdominal circumference.
Non obese diabetics are more prone to metabolic syndrome than morbidly obese individuals whom both have elevated Resistin levels. This is because, the visceral obesity of morbidly obese is due to general body condition
After Ileal Interposition operation, strong recovery obtained from resistin levels causes strong recovery pf metabolic syndrome findings as well.  After Ileal Interposition surgery, 95% of our patients discontinue all cholesterol and hypertension drugs.

 

Ghrelin: Ghrelin is the main hormone which provides appearance of sense of hunger. The actual production region is fundus which exists on upper side of the stomach.  Less hormone is produced from “E” cells in pancreas.  The purpose to make gastric tubing (sleeve gastrectomy) by removing fundus part of the stomach in Ileal Interposition is to suppress secretion of Ghrelin hormone. Rapid reduction appears in Ghrelin hormone levels after Ileal Interposition surgery.  Another cause for long term fullness sense that patients experience after the operation is reduction of Ghrelin.

 

Hormones Increasing Insulin Effects

Many different hormones or hormone-like substances are secreted from small intestines.  These substances are called “incretins” or “secretins”.

Incretins generally increase insulin production and activity and decrease resistance of tissues against insulin.

The most important incretins for metabolic surgery, namely Type 2 Diabetes are GLP-1 and GIP.  These two incretins are hormones of which effects have been examined and revealed better. They reduce, even eliminate insulin resistance by different ways.

GLP-1: It is abbreviation of Glucagon Like Polypeptide-1.  It is secreted from “L" cells in ileum.  It is strongly triggered by foods coming to ileum which are not digested and mixed with bile.  As understood from the name GLP-1, it is molecularly similar to Glucagon hormone.  So, it connects to receptors recognizing Glucagon in the liver, fat tissue and muscles in particular like Glucagon.  However, they do not stimulate any effect stimulated by Glucagon.  They block receptors and prevent connection of Glucagon.  They perform opposite function of Glucagon.

GLP-1 hormone,

1. increases beta cell count in pancreas.
2. Increases beta cell activity.
3. Increases insulin production.
4. Restores early insulin response.
5. Eliminates insulin resistance on liver, muscles and fat tissue.

Insulin resistance may be resolved completely by these effects of GLP-1.  For complete function of GLP-1 hormone, pancreas beta cell reserve should be preserved.  Therefore, Ileal Interposition surgery can not be applied for each patient with Type 2 Diabetes.  GLP-1 effect is very limited in the patients who exhausted or reduced reserves.  In fact, GLP-1 performs its stimulation in these patients as well.  However, if there is not any beta cell which will be stimulated and activated, the expected effect can not be obtained in any way.

GIP: It is a hormone known as Gastrointestinal Polypeptide or Glucose-dependent Insulinotropic Polypeptide.  It is actually secreted from duedonum.  It has similar effects with GLP-1.  Level does not decrease much in patients with Type 2 Diabetes.  However, it looses its efficiency somehow in Type 2 Diabetes.  GIP activity increases after ileal interposition.  It plays role in breaking resistance of insulin.  It stimulates pancreas and provided increase of insulin secretion.
It is considered that decrease of GIP efficiency in case of Type 2 Diabetes may due to anti-incretins which are secreted from duodenum but suppresses effects of incretins.  Secretion of these negatively effected incretins (anti-incretin) occurs by entering food into duodenum.  Food passage into duodenum is prevented by ileal interposition surgery.  Therefore, it is considered that secretion of anti-incretins decrease.

Ileal Interposition operation controls and fixes pathophysiological mechanisms of Type 2 Diabetes directly and immediately through these mechanisms which can be revealed today.  In the future, findings which will reveal metabolic effects of the surgery more and this development will affect drug industry as well.

For today, thanks to these dramatic therapeutic effects of ileal interposition, it is the only option which may treat diabetes strongly that none of the drugs or insulin therapy can achieve. Since the patients who obtain this strong treatment option do not experience any malabsorption, they do not pay any due for vitamin-mineral deficiency for lifetime.