Impaired Adipogenesis in Insulin Resistance: Pilot Clinical and In Vitro Studies

February 1, 2011 updated by: University of Vermont

Obesity is a strong risk factor for developing type 2 diabetes (T2DM), but the reasons for this are not fully understood. In particular, it is not known why some obese people develop T2DM while other obese individuals do not. This study tests whether differences in fat cells (adipocytes) are to blame. Even in adults, fat cells are constantly being formed to replace old fat cells and to respond to the body's need to store excess energy. The ability to form new fat cells may be diminished in some individuals, leading to larger fat cells. These large fat cells secrete hormones that may increase risk for T2DM. This study tests whether fat cells from obese insulin resistant subjects (who are at risk for developing T2DM) form at a slower rate than those from insulin sensitive subjects (who are at lower risk for developing T2DM).

To address this question we will recruit and study two groups of obese subjects, selected to be similar in age, gender and degree of obesity. One group of subjects will be obese and insulin resistant (the OIR group), while the other will be comparably obese, but insulin sensitive (OIS). Subjects will undergo a series of studies to characterize their metabolism including measurement of body fat by DEXA scanning, oral glucose tolerance (a test used to diagnose diabetes) and measurement of insulin sensitivity in response to an infusion of insulin (a research study used to classify patients into the OIR and OIS groups). Small samples of fat (from just under the skin of the belly and the buttocks) will obtained using a needle on two occasions over 12 weeks. During these 12 weeks, subjects will drink a small amount of water that contains a non-radioactive label. This labeled water will allow us to measure the rate of growth of new fat cells in the body. We will also look at the rate of growth of fat cells obtained from these biopsies in the laboratory.

The results of this study may tell us more about why certain obese people develop diabetes and why others do not. This might lead to new ways to prevent or treat T2DM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Overview of design: To address the specific aims of this study we will recruit and study two groups of obese subjects, selected to be similar in age, gender and BMI. Based on the results of an oral glucose tolerance test (OGTT) and hyperinsulinemic-glucose clamp, one group will be obese and insulin resistant (OIR) and one will be obese and insulin sensitive (OIS). Subjects will undergo measurement of body fat and fat distribution, oral glucose tolerance, in vivo insulin sensitivity, percutaneous needle biopsies of subcutaneous abdominal and gluteal fat and in vivo measurement of SVC and adipocyte turnover using the D2O DNA labeling technique. Adipocyte size and the expression of pro-inflammatory cytokines and adipokines will be compared in the two groups. Primary cultures of preadipocytes will be derived from subjects and proliferation and differentiation measured in vitro and compared to in vivo measures.

Measurement of adipocyte proliferation and differentiation in vivo: The stable isotope technique of Hellerstein et al. for the measurement of slowly dividing cells is based on the incorporation of deuterium oxide (D2O) into DNA. This method has been used to estimate rates of turnover of adipocytes and stromal vascular cells in healthy normal volunteers. It has not, to date, been employed to compare groups of subjects who may differ in their adipogenic propensity. A major objective of the study, therefore, is to evaluate the utility of this approach for quantifying in vivo differences in adipocyte and SVC turnover between groups that vary by insulin sensitivity and to compare the in vivo measures obtained using this technique with in vitro measures of adipogenesis.

Study Type

Observational

Enrollment (Actual)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Vermont
      • South Burlington, Vermont, United States, 05403
        • Fletcher Allen Health Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

36 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

  • Men and women age 40-65 who are obese (BMI>30)and weight stable for 6 months prior to enrollment.

Exclusion Criteria:

  • Acute or chronic medical conditions that would contraindicate participation in the research testing
  • Pregnant or nursing women
  • HbA1c>6.5%
  • Active alcohol or drug abuse
  • Weight >300 pounds.
  • Smoking

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
Men and Women over age 40 who are obese (BMI>30) and insulin-resistant.
Other: Administration of 70% deuterated water
Subjects will drink 70% deuterated water daily for 8 weeks.
2
Men and women over age 40 who are obese (BMI>30) and insulin-sensitive.
Other: Administration of 70% deuterated water
Subjects will drink 70% deuterated water daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
In vitro rates of adipocyte turnover
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vermont

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Richard E Pratley, MD, University of Vermont

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

November 16, 2007

First Submitted That Met QC Criteria

November 16, 2007

First Posted (Estimate)

November 19, 2007

Study Record Updates

Last Update Posted (Estimate)

February 2, 2011

Last Update Submitted That Met QC Criteria

February 1, 2011

Last Verified

September 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R21DK080386 (U.S. NIH Grant/Contract)
  • 1R21DK80386-1
  • 958

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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