Study of Changes in Skeletal Muscle After Caloric Restriction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00993460
Recruitment Status : Active, not recruiting
First Posted : October 12, 2009
Last Update Posted : April 4, 2018
Information provided by (Responsible Party):
Charles R. Flynn, Vanderbilt University

Brief Summary:
Research has shown that fat stored within muscles affects the muscle's sensitivity to insulin and ability to handle blood glucose. The purpose of this study is to examine the effects of weight loss surgery-induced caloric restriction on the accumulation and types of fats within skeletal muscle, as well as the effects of such caloric restriction on insulin sensitivity and inflammatory responses in skeletal muscle. The investigator proposes that caloric restriction will result in decreases in diacylglycerols enriched with saturated fat and increases in diacylglycerols enriched with monounsaturated fats.

Condition or disease

Detailed Description:

We hypothesize that in a setting of surgically-induced weight loss decrements in select DAGs result in improved glucose utilization, altered insulin signaling and decreased inflammatory responses. We propose to examine the impact of molecular DAG species accumulation on glucose utilization, insulin signaling and inflammation in skeletal muscle from morbidly obese subjects before/after 10% weight loss facilitated by Roux-en-Y Gastric Bypass (RYGB). We will compare these results to those from a control, normal weight cohort

The detected differences in DAG molecular species, insulin action, inflammatory responses between normal and obese subjects (before/after weight loss) will emphasize pathways coordinately altered as a consequence of adiposity and RYGB surgery. The primary endpoints for this study will be: Insulin sensitivity (glucose Rd, insulin levels, DAG mass, DAG species amounts).Secondary endpoints will be: FFA levels, inflammatory cytokine production, and insulin signaling in skeletal muscle.

Study Type : Observational
Estimated Enrollment : 24 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction
Study Start Date : March 2011
Actual Primary Completion Date : November 2013
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin
U.S. FDA Resources

Normal body weight
Female subjects, ages 21-65 yrs, with BMI of 21-27 kg/m2 with normal glucose tolerance.
Roux-en-Y gastric bypass
Female subjects ages 21-65 with insulin resistance and scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center will be studied before and 4-6 weeks after surgery.

Primary Outcome Measures :
  1. UPLC-ESI MS/MS profiling of lipd extracts from muscle biopsies to evaluate effects of gastric bypass induced-caloric restriction on diacylglycerol molecular species accumulation. [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. To evaluate the effects of gastric bypass induced-caloric restriction on skeletal muscle insulin action via a hyperinsulinemic-euglycemic clamp and profiling markers of insulin signaling. [ Time Frame: 1 year ]
  2. To evaluate the effects of gastric bypass induced-caloric restriction on lipid-mediated inflammatory responses by profiling cytokines and free fatty acids in blood and inflammation markers in skeletal muscle biopsies. [ Time Frame: 1 year ]

Biospecimen Retention:   Samples With DNA
Whole blood, plasma, muscle tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Female subjects approved for Roux-en-Y gastric bypass surgery at Vanderbilt University Medical Center.

Inclusion Criteria:

  • For Normal Weight Subjects:

    • Age 21-65 years
    • BMI of 21 to 27 kg/m2
    • Normal glucose tolerance as determined by OGTT on day of screening
    • No family history of diabetes
  • For Morbidly Obese Subjects:

    • Age 21-65 years
    • BMI of 30 to 65 kg/m2
    • Scheduled for Roux-en-Y gastric bypass at Vanderbilt Medical Center
    • Insulin resistant as determined by OGTT on day of screening

Exclusion Criteria (for all subjects):

  • Clinically significant heart disease
  • Clinically significant hepatic or renal disease
  • Pregnancy
  • Breastfeeding
  • Any abnormality that would preclude safe completion of study
  • Use of statins
  • Use of thiazide or furosemide diuretics, beta blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless subject has been on stable dose of such medications for the past 3 months before entering the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00993460

United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Principal Investigator: Charles R Flynn, PhD Vanderbilt University Medical Center
Study Chair: Naji Abumrad, MD Vanderbilt University Medical Center

Responsible Party: Charles R. Flynn, Assistant Professor, Vanderbilt University Identifier: NCT00993460     History of Changes
Other Study ID Numbers: IRB #091145
First Posted: October 12, 2009    Key Record Dates
Last Update Posted: April 4, 2018
Last Verified: April 2018

Keywords provided by Charles R. Flynn, Vanderbilt University:
Insulin sensitivity

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs