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

Study Overview
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Brief Summary
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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 We observed improvement of glycemic control and hemoglobin A1c, allied to reduction of medicines: insulin was withdrawn or significantly lowered.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
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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.

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

Conditions
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Diabetes Mellitus, Type 2, Insulin Resistance, Obesity

Intervention / Treatment
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* Procedure: Duodenal exclusion plus omentectomy
* Procedure: Duodenal exclusion without omentectomy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Duodenal exclusion plus total omentectomy | Procedure: Duodenal exclusion plus omentectomy<br>* 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.<br>* Other names: Duodenal-jejunal bypass plus omentectomy;|
| Active Comparator: 2<br>Duodenal exclusion without omentectomy | Procedure: Duodenal exclusion without omentectomy<br>* 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.<br>* Other names: Duodenal-jejunal bypass;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Changes in seric levels of adiponectin and other adipokines. |  | 2 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, type 2, Insulin resistance, Intra-Abdominal Fat, Omentum, duodenal exclusion, bariatric surgery, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, insulin, glucagon, ghrelin, adiponectin, Cytokines