Study of Changes in Skeletal Muscle After Caloric Restriction

NCT ID: NCT00993460

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2026-11-30

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.

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.

Conditions

Obesity

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Normal body weight

Female subjects, ages 21-65 yrs, with BMI of 21-27 kg/m2 with normal glucose tolerance.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Charles R. Flynn

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles R Flynn, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Naji Abumrad, MD

Role: STUDY_CHAIR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

IRB #091145

Identifier Type: -

Identifier Source: org_study_id