Clinical trial NCT01278823: Effect of Bariatric Surgery on Mechanisms of Type 2 Diabetes
Official title: Effect of Bariatric Surgery on Mechanisms of Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Type 2 Diabetes
Keywords: obesity
type 2 diabetes
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2011-01-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Test the effect of gastric bypass surgery on glycemic control in obese type 2 DM patients
timeFrame: 12 months
Secondary outcomes:
measure: Determine the effects of gastric bypass surgery on pancreatic beta cell function and incretin hormone secretion in obese type 2 dm patients
timeFrame: 12 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Bariatric and Metabolic Institute, Department of Pathobiology
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: John Kirwan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.