Clinical trial NCT00627484: Changes in Insulin Sensitivity After Weight Loss
Official title: Changes in Insulin Sensitivity After Weight Loss Induced by Diet or Bariatric Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Type 2 Diabetes Mellitus
Insulin Resistance
Keywords: Insulin resistance
Insulin sensitivity
bariatric surgery
diabetes
calorie restriction
body composition
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2008-03-03
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Insulin Sensitivity
timeFrame: 2-8 weeks
Secondary outcomes:
measure: Change in Body Composition
timeFrame: 2-8 weeks
measure: Change in Resting Energy Expenditure
timeFrame: Up to 4 hrs post-meal
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Judith Korner, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.