Effects of Caloric Restriction Alone Versus Postoperative Caloric Restriction Following Bariatric Surgery on Glucose Metabolism in Patients With Diabetes Mellitus

NCT01083108 | Terminated Phase 2

• 2 other identifiers: 10006410-DK-0064
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

Background:

• Bariatric surgery is the most effective way to achieve significant, long-term weight loss. It has also been shown to be an effective therapy for obese individuals with type 2 diabetes: more than 70 percent of patients no longer need medications for diabetes after surgery. This resolution of diabetes is predominately caused by marked weight loss resulting in improved insulin sensitivity. However, the beneficial effects of bariatric surgery on type 2 diabetes cannot be accounted for entirely by weight loss, because many bariatric surgery patients have resolution of diabetes within 1 week following bariatric surgery, even before they lose a clinically significant amount of weight.
• One possible reason for the rapid resolution of diabetes after bariatric surgery .is that during the first week after surgery, patients can eat very little (about 300 Calories per day). It is well known that reducing calories to this level improves diabetes. Another possibility is that changes in the flow of food through the intestines may improve diabetes. Evidence for this comes from the observation that patients after gastric bypass have better glucose levels than those who have gastric banding. Researchers are interested in determining how much of the improvement in diabetes in the first week after Roux-en-Y gastric bypass (RYGBP) surgery is due to restricting calories, and how much is due to other factors, such as bypassing the upper part of the small intestine. Objectives:
• To determine the change in total body insulin sensitivity after RYGBP compared to caloric restriction without surgery.
• To study possible reasons for improvements in diabetes after RYGBP. Eligibility: \- Individuals 18 to 60 years of age who have a body mass index (BMI) greater than 35 and have type 2 diabetes. Design: \- This is not a randomized study, and patients will not receive bariatric surgery as part of this study. Two groups of patients will be studied: those scheduled for RYGBP surgery and those not undergoing surgery.
• RYGBP Surgery Participants:
• Up to 3 weeks before surgery, participants will spend 2 nights and days at the Vanderbilt University Clinical Research Center or the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
• From 8 days before surgery, participants will begin an 800 Calorie per day liquid diet to prepare for surgery.
• After surgery and discharge, participants will be readmitted to the Clinical Research Center at Vanderbilt or NIH for further tests and diet monitoring. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.
• Non-surgery Participants:
• Participants will spend 2 nights and days in the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
• After the tests, participants will begin an 800 Calorie per day liquid diet for 8 days.
• After 8 days, participants will be readmitted to the Clinical Center at NIH for 1 week of further tests and a 300 Calorie per day diet. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.

Conditions

Obesity; Bariatric Surgery; Morbid Obesity; Diabetes Mellitus Type 2; Diet Therapy

Keywords

Behavioral Weight Loss Treatment; Bariatric Surgery; Diabetes Type II; Obesity; Adult; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• The primary outcome of the study is the change in total body insulin sensitivity due to RYGBP alone using the euglycemic hyperinsulinemic clamp technique.

  Insulin sensitivity will be determined using the gold standard euglycemic hyperinsulinemic clamp method, which directly measures total body insulin sensitivity as the glucose disposal rate, M, during steady state conditions of euglycemia and hyperinsulinemia. A two- stage clamp will be performed, using first a low-dose insulin infusion (to determine hepatic insulin sensitivity), followed by a high-dose insulin infusion (to determine muscle insulin sensitivity).

  2 years

Secondary Outcomes (1)

• The secondary outcomes are changes in insulin sensitivity, insulin secretion, and gut hormones due to caloric restriction alone, caloric restriction plus RYGBP, and RYGBP alone.

  2 years

Study Arms (2)

Non-surgical Arm

ACTIVE COMPARATOR

Low-calorie Diet

Other: Caloric Restriction

Surgical Arm

EXPERIMENTAL

Roux-en-Y Gastric Bypass

Other: Roux-en-Y Gastric Bypass

Interventions

Roux-en-Y Gastric Bypass OTHER

The surgical group will be studied before and 6 days after bariatric surgery.

Surgical Arm

Caloric Restriction OTHER

The non-surgical group will be studied before and after receiving a hypocaloric diet for 6 days mimicking the typical postoperative diet.

Non-surgical Arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Clinical diagnosis of Type 2 diabetes mellitus
• Age 18-60 years
• Body mass index greater than or equal to 35 kg/m(2)
• Either
• a. Patients scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center or University of Maryland
• b. Patients matched for race, sex, BMI (plus or minus 15%), and age (plus or minus 5 years) to RYGBP patients, above, but NOT scheduled for bariatric surgery.
• Subjects must have an endocrinologist or primary care provider who manages their diabetes.

You may not qualify if:

• Current use of insulin
• Use of exenatide, sitagliptin (or other dipeptidyl peptidase inhibitor), thiazolidinediones, or experimental diabetes medication within the past 3 months
• Medical condition that alters glucose metabolism (other than type 2 diabetes) or weight (e.g. chronic inflammatory diseases, monogenic obesity, Prader-Willi syndrome)
• Current use of medication that alters glucose metabolism (other than oral diabetes medications) or weight (e.g. corticosteroids, atypical antipsychotic drugs)
• Significant comorbidity that, in the opinion of the investigators, will increase risk to the subject, (e.g. current treatment for cancer, renal failure)
• Positive urine pregnancy test or plans to become pregnant during the clinical trial
• Psychiatric or cognitive disorder that will, in the opinion of the investigators, limit the subject's ability to comply with study procedures
• Body weight greater than 450 lbs
• History of previous bariatric surgical procedure or other surgery altering the length or arrangement of the intestines (e.g. Whipple procedure)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (3)

University of Maryland, Baltimore

Baltimore, Maryland, 21201-1595, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

• Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. doi: 10.2337/diabetes.52.1.102.

  PMID: 12502499 BACKGROUND

• Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia. 2005 Nov;48(11):2221-8. doi: 10.1007/s00125-005-1949-2. Epub 2005 Oct 5.

  PMID: 16205882 BACKGROUND

• Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999 Jun 2;281(21):2005-12. doi: 10.1001/jama.281.21.2005.

  PMID: 10359389 BACKGROUND

MeSH Terms

Conditions

Obesity; Obesity, Morbid; Diabetes Mellitus, Type 2

Interventions

Gastric Bypass; Caloric Restriction

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Bariatric Surgery; Bariatrics; Obesity Management; Therapeutics; Gastroenterostomy; Anastomosis, Surgical; Surgical Procedures, Operative; Digestive System Surgical Procedures; Diet Therapy; Nutrition Therapy; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Kristina I Rother, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2010
• First Posted: March 9, 2010
• Study Start: March 31, 2011
• Primary Completion: May 22, 2013
• Study Completion: December 13, 2019
• Last Updated: December 17, 2019

Record last verified: 2019-12-13

Locations

US (3)