Treatment of Type 2 Diabetes Mellitus by Duodenal Exclusion Associated With Omentectomy: Clinical and Hormonal Study

Obesity Clinical Trial

Official title:

Clinical and Hormonal Study of a New Surgical Treatment of Type 2 Diabetes Mellitus: Duodenal Exclusion Associated With Omentectomy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00566215
• Other study ID #: LIMED0003
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 30, 2007
• Last updated: July 22, 2010
• Start date: July 2007
• Est. completion date: June 2009

Study information

• Verified date: July 2010
• Source: University of Campinas, Brazil
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

Based in a surgery technique studied in a non-obese diabetic mouse model by Rubino and Marescaux(2004), wich reversed diabetes in those animals, we have performed a previous study in human volunteers with type 2 diabetes and overweight (non-obese). The surgery is a duodenal exclusion in wich the stomach volume is kept intact. We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered.

Further improvement of diabetes could be achieved by intervention in insulin resistance, another factor of diabetes pathophysiology. As that factor is related to visceral fat, we hypothesize that surgical removal of the major omentum, a great component of central adiposity, could beneficial .

This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery plus total omentectomy, by the method of standardized meal stimulus and insulin tolerance test, in human non-obese volunteers with diabetes type 2 and known insulin secretion capacity.

The previously studied volunteers submitted to duodenal exclusion without omentectomy will be the control group.

Description:

Diabetes reversion is observed after bariatric surgeries even before significant weight loss could explain it, mainly in predominantly malabsorptive procedures, followed by those combining malabsorption and gastric restriction. Changes in the hormonal communication between the digestive system (incretins)and the pancreas would explain the antidiabetogenic role of the surgery, so this effect could be obtained in nonobese, diabetic individuals.

Based in a surgery technique studied in a non-obese diabetic mouse model by Rubino and Marescaux(2004), wich reversed diabetes in those animals, we have performed a previous study in human volunteers with type 2 diabetes and overweight (non-obese). The surgery is a duodenal exclusion: the stomach volume is kept intact, maintaining the caloric ingestion and the weight reduces less than 5%, without the potential nutritional deprivations commonly seen in the bariatric surgery. We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered. An standardized mixed meal tolerance test showed favorable changes in the gastrointestinal hormones that stimulate insulin secretion (incretins): increase of GLP-1 and reduction of GIP.

Further improvement of diabetes could be achieved by intervention in insulin resistance, another factor of diabetes pathophysiology. As that factor is related to visceral fat, we hypothesize that surgical removal of the major omentum, a great component of central adiposity, could beneficial .

In fact, surgical removal of visceral fat in rodents improves insulin sensitivity. A pilot study in human, obese volunteers submitted to gastric adjustable band was promising int this aspect.

This study will evaluate the mechanisms of amelioration of type 2 diabetes mellitus after duodenal exclusion surgery plus total omentectomy , by the method of standardized meal stimulus and insulin tolerance test, in human non-obese, volunteers with diabetes type 2 and known insulin secretion capacity.

The previously studied volunteers submitted to duodenal exclusion without omentectomy will be the control group.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Obesity

Intervention

Procedure:
• Duodenal exclusion plus omentectomy
Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create a 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. Additionally, total omentectomy is performed.
• Duodenal exclusion without omentectomy
Under open laparotomy, a duodenum section 2cm below the pylorus and a jejunum section below Treitz's Angle to create a 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.

Locations

Country	Name	City	State
Brazil	LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)	Campinas	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Campinas, Brazil

Country where clinical trial is conducted

Brazil, 

References & Publications (6)

Barzilai N, She L, Liu BQ, Vuguin P, Cohen P, Wang J, Rossetti L. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes. 1999 Jan;48(1):94-8. — View Citation

Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002 Oct;51(10):2951-8. — View Citation

Geloneze B, Geloneze SR, Fiori C, Stabe C, Tambascia MA, Chaim EA, Astiarraga BD, Pareja JC. Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal-jejunal exclusion. Obes Surg. 2009 Aug;19(8):1077-83. doi: 10.1007/s11695-009 — View Citation

Pitombo C, Araújo EP, De Souza CT, Pareja JC, Geloneze B, Velloso LA. Amelioration of diet-induced diabetes mellitus by removal of visceral fat. J Endocrinol. 2006 Dec;191(3):699-706. — View Citation

Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004 Jan;239(1):1-11. — View Citation

Thörne A, Lönnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord. 2002 Feb;26(2):193-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Changes in body weight and fat distribution after intervention		1 month, 2 months, 3 months, 6 months and 1 year	No
Secondary	Changes in seric free fatty acids and lipoproteins		one month, 2 months, 3 months, 6 months and 1 year	No
Secondary	Regression of carotid intima-media thickness		1 month, 3 months, 6 months and 1 year	No
Secondary	Changes in seric levels of adiponectin and other adipokines.		2 months, 6 months and 1 year	No
Secondary	Improvement of insulin sensitivity as measured by insulin tolerance test.		1 month, 3 months, 6 months and 1 year	No