Obesity, Weight Loss, and Cardiovascular Disease Risk

March 12, 2013 updated by: Tracey McLaughlin, Stanford University

GCRC-CAP-Tracey McLaughlin, MD

The goal of the study is to define the roles played by resistance to insulin-mediated glucose disposal (insulin resistance) and circulating plasma insulin concentrations in: 1) ability to lose weight; 2) reduction of risk for coronary heart disease as a result of weight loss. We hypothesize that in the setting of caloric restriction, manipulating endogenous insulin concentrations will not alter ability of subjects to lose weight, but will lead to different reduction in CHD risk factors. To test this hypothesis, two parallel studs will be performed. First, obese insulin-resistant individuals will be randomized to one of two equally-hypocaloric diets that vary moderately in proportion of carbohydrate and mono/polyunsaturated fats (lower carbohydrate diet will be associated with greater reduction in endogenous insulin secretion). Second, diabetics treated with insulin secretagogues will be compared to diabetics treated with insulin sensitizers with respect to the same outcomes (secretagogues increase insulin secretion and insulin sensitizers decrease insulin concentrations). Endpoints include weight loss, change in insulin resistance, blood pressure, lipid and lipoproteins, markers of endothelial function, daylong insulin and glucose concentrations: these will be compared, in each of the parallel studies, between the group with insulin-stimulating intervention vs the group with the insulin-sparing intervention.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

While obesity, insulin resistance, and diabetes are highly associated, it is not clear whether insulin resistance and compensatory hyperinsulinemia play important roles in the tendency to gain weight and/or inability to lose weight. The role of hyperinsulinemia in coronary heart disease (CHD)is also unclear. The specific aims of the proposed research are as follows:

  1. To compare insulin resistant versus insulin sensitive nondiabetic overweight individuals with respect to their ability to lose weight on a low calorie diet. CHD risk factors before and after weight loss will also be assessed to determine the degree to which insulin resistance is associated with CHD risk, as well as the impact that differences in insulin resistance have on the metabolic benefits of weight loss
  2. To determine if weight loss and its associated metabolic benefits vary as a function of the relative amounts of dietary fat and carbohydrate in hypocaloric diets. Because high carbohydrate diets increase insulin secretion, the relationship between dietary composition and change in circulating insulin concentrations will be analyzed with respect to both weight loss and CHD risk factors.
  3. To quantify and compare the improvement in glycemic control and CHD risk factors associated with weight loss in obese type 2 diabetics, while being treated with 1) an insulin secretagogue (sulfonylurea) or 2) an insulin sensitizer (thiazolidinedione). Manipulation of plasma insulin concentrations with these medications will provide a mechanism by which to evaluate the impact of circulating insulin concentrations on the described outcome measures.
  4. A subgroup of overweight/obese premenopausal women with PCOS will be studied using two diets in crossover design with regard to macronutrient effects on endogenous hyperinsulinism. For this subgroup age range will be 18-50 years, BMI 25-50 kg/m2.
  5. In order to increase our data and therefore increase our better understanding of fat cells and insulin resistance and changes in fat cells with weight loss we would like to increase our participant enrollment to 550 all to be enrolled at Stanford University Medical Center recruiting Bariatric participants:

Age for Bariatric patients 30-65 men and women BMI 27-no upper limit Currently we have completed all participants except the bariatric and post bariatric population and those with hypoglycemia following bariatric surgery.

The ethnic background of subjects reflects Stanford's patient population.

Study Type

Interventional

Enrollment (Anticipated)

550

Phase

  • Not Applicable

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
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • BMI 30-35
  • age 35-65
  • nondiabetic by fasting plasma glucose concentration
  • no active major organ diseases
  • insulin resistant or insulin sensitive

Exclusion Criteria:

  • anemia
  • pregnant
  • major organ disease
  • active malignancy
  • eating disorder
  • active psychiatric illness
  • chronic inflammatory conditions

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

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Weight loss

Secondary Outcome Measures

Outcome Measure
Lipid/lipoprotein changes
Blood pressure changes
Insulin resistance changes
Endothelial function changes

Collaborators and Investigators

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

Sponsor

Stanford University

Investigators

  • Principal Investigator: Dr Tracey Lynn McLaughlin, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

October 1, 2000

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

March 13, 2013

Last Update Submitted That Met QC Criteria

March 12, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RR16071-01

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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