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

Phase 1
Terminated
Conditions
Obesity
Diabetes Mellitus, Type 2
Insulin Resistance
Interventions
Procedure: Duodenal exclusion plus omentectomy
Procedure: Duodenal exclusion without omentectomy
Registration Number
NCT00566215
Lead Sponsor
University of Campinas, Brazil
Brief 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 We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered.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.

Detailed 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 & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1Duodenal exclusion plus omentectomyDuodenal exclusion plus total omentectomy
2Duodenal exclusion without omentectomyDuodenal exclusion without omentectomy
Primary Outcome Measures
NameTimeMethod
Improvement or reversal of type 2 diabetes mellitus7 days, 14 days, 21 days, 1 month, 2 months, 3 months, six months and one year
Secondary Outcome Measures
NameTimeMethod
Changes in the secretion pattern of incretins, insulin and glucagon after intervention, as measured by standardized mixed meal tolerance test2 months, 6 months and 1 year
Changes in seric free fatty acids and lipoproteinsone month, 2 months, 3 months, 6 months and 1 year
Improvement of insulin sensitivity as measured by insulin tolerance test.1 month, 3 months, 6 months and 1 year
Changes in seric levels of adiponectin and other adipokines.2 months, 6 months and 1 year
Changes in body weight and fat distribution after intervention1 month, 2 months, 3 months, 6 months and 1 year
Regression of carotid intima-media thickness1 month, 3 months, 6 months and 1 year

Trial Locations

Locations (1)

LIMED (Laboratory of Investigation of Metabolism and Diabetes)/GASTROCENTRO/Univeristy of Campinas (UNICAMP)

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Campinas, SP, Brazil

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