Surgical Treatment of Non-obese Type 2 Diabetic Patients With Duodenal Exclusion
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

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).

      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.
    

Intervention name(s): Duodenal exclusion surgery
Intervention type(s): Procedure
Intervention description(s): 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 intervention name(s): Duodeno-jejunal exclusion; Duodenal-jejunal bypass
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: diabetes mellitus, type 2; duodenal exclusion; bariatric surgery; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; insulin; glucagon; ghrelin