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

Phase 1
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Procedure: Duodenal exclusion surgery
Registration Number
NCT00566358
Lead Sponsor
University of Campinas, Brazil
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
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
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Duodenal exclusion surgeryDuodenal exclusion
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.
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
Secondary Outcome Measures
NameTimeMethod
Changes in body weight and fat distribution after intervention1 month, 2 months, 3 months, 6 months and 1 year
Changes in seric free fatty acids and lipoproteinsone 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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