Effect of Bariatric Surgery on Mechanisms of Type 2 Diabetes

NCT ID: NCT01278823

Last Updated: 2019-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2017-02-15

Brief Summary

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The purpose of this study is to determine the effects of bariatric surgery on blood sugar control and underlying mechanisms that contribute to type 2 diabetes in men and women with a BMI between 27 and 42. Sixty subjects will be randomized to either undergo the roux-en-y gastric bypass operation or intensive medical, dietary and exercise management.

Detailed Description

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Obesity and type 2 diabetes mellitus (T2DM) are two of the greatest public health problems of the 21st century. Lifestyle changes and pharmacotherapy, which are mainstay treatments for T2DM have had limited success. More intensive lifestyle weight management such as in the Look AHEAD trial reported an 8.6% weight loss after 1 year, while the Diabetes Prevention Program reported a 7% weight loss after 2 years, and a 58% decrease in the risk of developing T2DM. In contrast,we have observed a 31% weight loss together with 83% remission of T2DM in severely obese patients after Roux-en-Y gastric bypass (RYGB) surgery. However, direct evidence of the glycemic benefits of bariatric surgery from randomized control trials is lacking; there is no clear consensus that RYGB surgery is a good treatment option for moderately obese T2DM patients; and the mechanisms responsible for reversing T2DM after surgery remain unclear but may involve pancreatic insulin secretion and skeletal muscle and hepatic insulin resistance.

The objective of this application is to evaluate the effects of RYGB surgery on glycemic control and underlying mechanisms that contribute to T2DM in obese subjects (BMI: 30-40 kg/m2). Our central hypothesis is that RYGB surgery will reduce hyperglycemia via reversal of beta-cell dysfunction and decrease hepatic and peripheral insulin resistance. The approach requires a 12-month randomized controlled trial. The rationale is based on data showing that RYGB lowers fasting and postprandial glucose, and increases the GLP-1 response to a meal. However, the therapeutic efficacy of RYGB surgery in obesity-related T2DM needs to be demonstrated in a randomized trial.

Conditions

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Obesity Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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surgery

Surgery: laparoscopic roux en y gastric bypass operation

Group Type EXPERIMENTAL

laparoscopic roux en y gastric bypass operation

Intervention Type PROCEDURE

roux en y gastric bypass operation

Medical treatment

Medical Treatment: Comprehensive medical management of diabetes including medications, diet intervention, lifestyle modification, exercise regimen

Group Type ACTIVE_COMPARATOR

medical management

Intervention Type OTHER

latest type 2 diabetes medications, lifestyle/behavior modification and dietary regimen

Interventions

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laparoscopic roux en y gastric bypass operation

roux en y gastric bypass operation

Intervention Type PROCEDURE

medical management

latest type 2 diabetes medications, lifestyle/behavior modification and dietary regimen

Intervention Type OTHER

Other Intervention Names

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bariatric surgery meal replacement exercise group support

Eligibility Criteria

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Inclusion Criteria

* candidate for general surgery
* 18 to 60 years old
* BMI 27-43
* type 2 diabetes
* willing to participate in either study arm
* understand and comply with requirements of each arm
* not pregnant
* willing to use reliable birth control for duration of study

Exclusion Criteria

* prior bariatric surgery of any type
* prior complex abdominal surgery
* abdominal, thoracic, pelvic, obstetrical surgery within last 6 months
* significant cardiovascular disease
* kidney disease with a creatinine greater than or equal to 1.8 mg/dl
* chronic liver disease except for NAFLD/NASH
* celiac, malabsorptive, inflammatory bowel disorders
* psychiatric disorders requiring 3 or more medications
* pregnancy
* cancer except squamous or basal cell skin cancer or cancer in remission
* anticoagulation therapy that can't be stopped for surgery
* clotting disorders
* severe pulmonary disease
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

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Philip Schauer

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Kirwan, PhD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Cleveland Clinic Bariatric and Metabolic Institute, Department of Pathobiology

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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Kirwan JP, Axelrod CL, Kullman EL, Malin SK, Dantas WS, Pergola K, Del Rincon JP, Brethauer SA, Kashyap SR, Schauer PR. Foregut Exclusion Enhances Incretin and Insulin Secretion After Roux-en-Y Gastric Bypass in Adults With Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4192-e4201. doi: 10.1210/clinem/dgab255.

Reference Type DERIVED
PMID: 33870426 (View on PubMed)

Related Links

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https://weightloss.clevelandclinic.org

Cleveland Clinic Bariatric and Metabolic Institute web site

Other Identifiers

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1R01DK089547

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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