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Study of Changes in Skeletal Muscle After Caloric Restriction

Sponsor
Vanderbilt University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00993460
Collaborator
(none)
24
Enrollment
1
Location
164.1
Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

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 Intervention/Treatment Phase

    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 Design

    Study Type:
    Observational
    Anticipated Enrollment :
    24 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction
    Study Start Date :
    Mar 1, 2011
    Actual Primary Completion Date :
    Nov 1, 2013
    Anticipated Study Completion Date :
    Nov 1, 2024

    Arms and Interventions

    Arm Intervention/Treatment
    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.

    Outcome Measures

    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. [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. [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. [1 year]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 65 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Vanderbilt University Medical Center Nashville Tennessee United States 37232

    Sponsors and Collaborators

    • Vanderbilt University

    Investigators

    • Principal Investigator: Charles R Flynn, PhD, Vanderbilt University Medical Center
    • Study Chair: Naji Abumrad, MD, Vanderbilt University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Charles R. Flynn, Assistant Professor, Vanderbilt University
    ClinicalTrials.gov Identifier:
    NCT00993460
    Other Study ID Numbers:
    • IRB #091145
    First Posted:
    Oct 12, 2009
    Last Update Posted:
    Feb 28, 2022
    Last Verified:
    Feb 1, 2022
    Keywords provided by Charles R. Flynn, Assistant Professor, Vanderbilt University
    Obesity
    Insulin sensitivity
    Inflammation
    Additional relevant MeSH terms:
    Obesity

    Study Results

    No Results Posted as of Feb 28, 2022