Study of Changes in Skeletal Muscle After Caloric Restriction



Status:Active, not recruiting
Conditions:Obesity Weight Loss
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:21 - 65
Updated:4/17/2018
Start Date:March 2011
End Date:November 2019

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Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction

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.

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.

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
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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Nashville, TN
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