Changes in Insulin Sensitivity After Weight Loss

Changes in Insulin Sensitivity After Weight Loss Induced by Diet or Bariatric Surgery

This study is designed to compare the changes in insulin sensitivity as well as gastrointestinal hormone levels in diabetic and non-diabetic obese individuals who are undergoing weight loss procedures. The main hypothesis of this study is that weight loss induced by gastric bypass will induce a greater improvement in insulin sensitivity compared with gastric banding or low calorie diet. Subjects will be studied before and after weight loss. Studies consist of intravenous glucose tolerance test, body composition analysis, meal test, and energy expenditure.

Study Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes Mellitus; Insulin Resistance
• Intervention / Treatment: Procedure: Gastric bypass; Procedure: Gastric banding; Behavioral: Very low calorie diet; Procedure: Sleeve gastrectomy

Detailed Description

Patients who are scheduled for gastric bypass (GBP), sleeve gastrectomy (SG), or simple caloric restriction with gastric banding (BND) or a very low calorie diet (VLCD) will be examined at baseline weight, and when 6-10% total body weight has been lost. We will measure insulin sensitivity with an intravenous glucose tolerance test, and fasting levels of hormones that regulate food intake and insulin sensitivity, such as ghrelin, peptide YY (PYY), glucagon-like peptide 1 (GLP1) and leptin. Fat mass and skeletal muscle mass will be measured by dual photon absorptiometry (DXA). We will also measure the hormonal and thermic response to food with a liquid test meal and energy expenditure by indirect calorimetry. This measures how many calories are burned at rest and the in response to food. Subjects with diabetes will continue to be studied with the same protocol on an annual basis out to 5 years in order to determine the rate of remission of diabetes and the durability of this effect as subjects tend to regain some body weight over time.

Subjects with diabetes will also be followed every three months for the first year after the initial weight loss for HbA1c and fasting glucose levels. The results of this study may lead to new understanding about changes in insulin sensitivity, body composition and hormonal profile, as well as changes in energy expenditure with weight loss after bariatric surgery or with simple caloric restriction. With this greater understanding, new treatments for obesity and diabetes, that do not require surgery, may be developed.

• Study Type: Observational
• Enrollment (Actual): 119

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects will be recruited by physician referral and from outpatient obesity, bariatric surgical clinics and endocrinology clinics at Columbia University Medical Center as well as from the Medical Center Community and metropolitan area via IRB-approved flyers and internet postings. Subjects will also be recruited from the following website: www.craigslist.com using the same posting format of the IRB-approved flyers.

Description

Inclusion criteria:

• Non-diabetic obese (BMI > 30) adult men and women between the ages of 18 and 75 scheduled to undergo

  • gastric bypass (GBP)
  • gastric banding (BND)
• Type 2 diabetes (HbA1c 6-12%) adult men and women between the ages of 18 and 75 scheduled to undergo gastric bypass.
• Type 2 diabetes (HbA1c 6-12%) adult men and women between the ages of 18 and 65 for weight reduction with a very low caloric diet (VLCD).
• Type 2 diabetes mellitus scheduled to undergo sleeve gastrectomy (SG).

Exclusion criteria:

• Pregnancy.
• Age > 75 for surgery groups; Age > 65 for VLCD group.
• Treatment with glucocorticoids, anti-depressants, anti-psychotics, neuroleptics, weight loss medications, experimental medication.
• Greater than a 5% change in total body weight in the 90 days prior to the study.
• History of untreated gallstones; hepatic or renal insufficiency, abnormal thyroid stimulating hormone (TSH).
• Use of thiazolidinedione therapy.
• HbA1c > 12%.
• Use of dipeptidyl peptidase IV (DPP-IV) inhibitor or glucagon-like peptide 1 receptor (GLP-1R) agonist for greater than 12 months within 3 months of the study.
• Fasting triglycerides > 400.
• Significant cardiovascular, neurologic, renal, gastrointestinal, or hematologic disease.
• Inability to comply with or understand the study protocol as ascertained by the PI.
• We will not exclude individuals with body weight > 145 kg, but we do recognize that such individuals are above the table weight limitations of the dual-energy x-ray absorptiometry (DEXA) scan and body composition data will be unavailable for those individuals.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1: GBP non-diabetic; Non-diabetic subjects scheduled to receive gastric bypass	Procedure: Gastric bypass; NOTE: the surgery is not paid for by the study; Other Names: GBP
Group 2: BND non-diabetic; Non-diabetic subjects scheduled to receive gastric banding	Procedure: Gastric banding; NOTE: the surgery is not paid for by the study; Other Names: BND
Group 3: GBP diabetic; Diabetic subjects scheduled to receive gastric bypass	Procedure: Gastric bypass; NOTE: the surgery is not paid for by the study; Other Names: GBP
Group 4: VLCD diabetic; Diabetic subjects scheduled to receive very low calorie diet	Behavioral: Very low calorie diet; Weight loss with calorie restricted liquid diet. Subject will be asked to stay in our in-patient research unit for 2-3 weeks and consume only those foods supplied by our bionutrition unit. Expected weight loss should be between 7-10% of body weight. Subjects will receive the diet at no cost and will be compensated for their time.; Other Names: VLCD
Group 5: SG diabetic; Diabetic subjects scheduled to receive sleeve gastrectomy	Procedure: Sleeve gastrectomy; NOTE: the surgery is not paid for by the study; Other Names: SG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insulin Sensitivity	Measured by frequently sampled intravenous glucose tolerance test (FSIVGTT)	2-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Composition	Measured by dual energy x-ray absorptiometry (DXA)	2-8 weeks
Change in Resting Energy Expenditure	Measured by indirect calorimetry using a Hood Calorimeter	Up to 4 hrs post-meal

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Judith Korner, MD,PhD, Columbia University

Publications and helpful links

General Publications

• Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, McMahon DJ, Korner J. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes. 2013 Sep;62(9):3027-32. doi: 10.2337/db12-1762. Epub 2013 Apr 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2005
• Primary Completion (Actual): June 17, 2018
• Study Completion (Actual): June 17, 2018

Study Registration Dates

• First Submitted: February 28, 2008
• First Submitted That Met QC Criteria: February 28, 2008
• First Posted (Estimate): March 3, 2008

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: diabetes; Insulin resistance; bariatric surgery; body composition; Insulin sensitivity; calorie restriction
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Endocrine System Diseases; Diabetes Mellitus; Body Weight; Hyperinsulinism; Body Weight Changes; Hypersensitivity; Diabetes Mellitus, Type 2; Weight Loss; Insulin Resistance
• Other Study ID Numbers: AAAB2401; R21DK081050 (U.S. NIH Grant/Contract); DK072011 (Other Grant/Funding Number: NIDDK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED