Surgical Treatment of Non-obese Type 2 Diabetic Patients With Duodenal Exclusion

Sponsor

University of Campinas, Brazil (Other)

Overall Status

Completed

CT.gov ID

NCT00566358

Collaborator

Ethicon Endo-Surgery (Industry)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Diabetes reversion is observed after bariatric surgeries even before significant weight loss could explain it, mainly in predominantly malabsorptive procedures (98,9% for biliopancreatic diversion or duodenal switch), followed by those combining malabsorption and gastric restriction (83,7% for Roux-en-Y gastric bypass). Changes in the hormonal communication between the digestive system and the pancreas would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

In order to try this hypothesis, RUBINO and MARESCAUX (2004) studied the gastrojejunal bypass (duodenal exclusion)in an mouse model of diabetes without obesity. In their technique the stomach volume is kept intact, maintaining the caloric ingestion and the weight of the animals. There was a fast improvement of diabetes, independent of diet and weight, without the potential nutritional deprivations commonly seen in the bariatric surgery like iron and vitamin deficiency.

This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery in human non-obese, diabetic volunteers and known insulin secretion capacity, by the method of standardized meal stimulus. It is expected to be secondary to changes in the gastrointestinal hormones that stimulate insulin secretion (incretins).

The knowledge about the clinical outcomes of this technique in humans and the description of the secretion pattern of gastrointestinal hormones after the surgery may contribute to the implementation of this surgery as a new therapeutic option for overweight (non-obese) diabetic patients.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Procedure: Duodenal exclusion surgery	Phase 1/Phase 2

Detailed Description

There is large recovery of insulin sensibility after bariatric surgery, as the patients get closer to ideal weight. Diabetes reversion is more frequent after predominantly malabsorptive procedures (98,9% for biliopancreatic diversion or duodenal switch), followed by those combining malabsorption and gastric restriction (83,7% for Roux-en-Y gastric bypass). Glycemia normalization occurs in an early phase of the postoperative period, even before significant weight loss could explain it. These techniques have in common a bypass of the duodenum and part of the jejunum. Many peptides are released in this segments that regulate pancreatic beta cells (insulin producers) either in physiological state or in diabetes. Anatomical-functional changes in the enteroinsular axis would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

In order to try this hypothesis, RUBINO and MARESCAUX (2004) studied the gastrojejunal bypass (duodenal exclusion)in Goto-Kakizaki mice (GK), the most used animal model of diabetes without obesity. In their technique the stomach volume is kept intact, maintaining the caloric ingestion and the weight of the animals. There was a fast improvement of diabetes, independent of diet and weight. The authors concluded that this procedure should be applied in humans for reversal of diabetes without the potential nutritional deprivations commonly seen in the bariatric surgery like iron and vitamin deficiency.

The amelioration of diabetes after bariatric surgery is related to the modulation of production of gastrointestinal hormones relevant to the insulin production (incretin effect).

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Lightening the Hormonal Mechanisms of Surgical Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Surgery

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Duodenal exclusion	Procedure: Duodenal exclusion surgery Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create an excluded biliopancreatic limb of 150cm. A Roux-in-Y retrocolic anastomosis of the alimentary limb promotes the gastrojejunal continuity and the anastomosis of the excluded biliopancreatic limb is done 100cm below the jejunal-pyloric union. Other Names: Duodeno-jejunal exclusion Duodenal-jejunal bypass

Arm

Intervention/Treatment

Experimental: 1

Duodenal exclusion

Procedure: Duodenal exclusion surgery

Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create an excluded biliopancreatic limb of 150cm. A Roux-in-Y retrocolic anastomosis of the alimentary limb promotes the gastrojejunal continuity and the anastomosis of the excluded biliopancreatic limb is done 100cm below the jejunal-pyloric union.

Other Names:

Duodeno-jejunal exclusion

Duodenal-jejunal bypass

Outcome Measures

Primary Outcome Measures

Improvement or reversal of type 2 diabetes mellitus [7 days, 14 days, 21 days, 1 month, 2 months, 3 months, six months and one year.]
Changes in the secretion pattern of incretins, insulin and glucagon after intervention, as measured by standardized mixed meal tolerance test [2 months, 6 months and 1 year]

Secondary Outcome Measures

Changes in body weight and fat distribution after intervention [1 month, 2 months, 3 months, 6 months and 1 year]
Changes in seric free fatty acids and lipoproteins [one month, 2 months, 3 months, 6 months and 1 year]
Regression of carotid intima-media thickness [1 month, 3 months, 6 months and 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age: 18 to 60 years.
BMI between 25 and 29,9 kg/m².
Weight variance less than 5% in the last 3 months.
Previous diagnosis of diabetes type 2.
Insulin requirement, alone or along with oral agents
Capacity to understand the procedures of the study.
To agree voluntarily to participate of the study, signing an informed consent.

Exclusion Criteria:

Positive Anti-GAD antibodies
Laboratorial signal of probable failure of insulin production, i. e., seric peptide C lesser than 1 ng/mL.
History of hepatic disease like cirrhosis or chronic active hepatitis.
Kidney dysfunction (creatinine > 1,4 mg/dl in women and > 1,5 mg/dl in men).
Hepatic dysfunction: ALT and/or AST 3x above upper normal limit.
Recent history of neoplasia (< 5 years).
Use of oral or injectable corticosteroids for more than consecutive 14 days in the last three months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)	Campinas	SP	Brazil

Sponsors and Collaborators

University of Campinas, Brazil
Ethicon Endo-Surgery

Investigators

Principal Investigator: Bruno Geloneze, MD, PhD, University of Campinas (UNICAMP)
Principal Investigator: José Carlos Pareja, MD, PhD, University of Campinas (UNICAMP)