The Effects of a Moderate Weight Loss on Insulin Resistance

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Yale University
Sponsor:
Collaborator:
Howard Hughes Medical Institute
Information provided by (Responsible Party):
Kitt Petersen, Yale University
ClinicalTrials.gov Identifier:
NCT02193295
First received: June 25, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes.


Condition Intervention
Insulin Resistance
Behavioral: Dietary consultations

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Effects of a Moderate Weight Loss on Muscle and Liver Fat Content and Reversal of Insulin Resistance

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Improvements in insulin sensitivity [ Time Frame: up to 6 months intervention to examine whether insulin sensitivity has improved significantly after the moderate weight reduction ] [ Designated as safety issue: No ]
    Insulin sensitivity will be assessed using the insulin/glucose clamp, liver and muscle fat will be measured using 1H magnetic resonance spectroscopy (MRS) and both results from the clamp and MRS compared to baseline values before the weight reduction intervention.


Estimated Enrollment: 35
Study Start Date: October 2002
Estimated Study Completion Date: October 2022
Estimated Primary Completion Date: October 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lifestyle Intervention
Caloric Restriction. One arm.
Behavioral: Dietary consultations
Dietary consultations and caloric restriction to reduce liver and intra myocellular fat content and improve tissue specific insulin sensitivity

Detailed Description:

In this study, we will examine whether a small weight loss in lean, insulin-resistant offspring of type 2 diabetic patients will improve insulin resistance. The control group will consist of subjects matched for gender, age and body weight with no family history of diabetes. Before and after weight loss, rates of basal and insulin stimulated whole body glucose metabolism will be measured using [6,6-2H] glucose during a 3 hour basal period and a 4 hour euglycemic hyperinsulinemic (20 mU/m2-min) clamp. Rates of whole body lipolysis will be determined using [2H5] glycerol, localized rates of lipolysis will be measured using the microdialysis technique and muscle PI 3-kinase activity will be assessed in muscle biopsies. FFA metabolites (fatty acyl CoA, ceramides, diacylglycerol) will be measured in fat tissue collected from the abdominal subcutaneous fat cell depot. Body composition will be determined with bioelectrical impedance and whole body MRI; IMCL will be measured with MRS. Before and after weight loss, insulin secretion will be measured with the hyperglycemic clamp (as described under Day 2 Hyperglycemic Clamp).

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy, sedentary, non-smoking and not taking any medications other than birth control pills.
  • Hematocrit >35%
  • Subjects will have no systemic or organ disease including diabetes.
  • Subjects will have no history eating disorders.
  • Women must be using a form of birth control (sexual abstinence, birth control pills, Norplant, IUD or condoms) and will be studied between day 0 and 7 of their menstrual cycle.
  • Those who are taking birth control pills or have had a hysterectomy may be studied at any time.
  • Physical activity will be assessed using a standard questionnaire with an activity index cut off at 2.3.

Exclusion Criteria:

  • Any subject, who does not fit the inclusion criteria. Including history of eating disorders, any systemic and organ disease including diabetes.
  • Hematocrit <35%.
  • Women of childbearing potential, who are not using contraception (as mentioned above) or who are not abstinent.
  • Subjects who have a regular exercise regimen will not be enrolled.
  • Metal implants and/or body piercing, which cannot be removed before the MR studies.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02193295

Contacts
Contact: Kitt Petersen, MD 203-688-4106 kitt.petersen@yale.edu

Locations
United States, Connecticut
Yale Center for Clinical Investigation HRU Recruiting
New Haven, Connecticut, United States, 06520
Contact: Kitt Petersen, MD    203-688-4106      
Principal Investigator: Kitt Petersen, MD         
Sponsors and Collaborators
Yale University
Howard Hughes Medical Institute
Investigators
Principal Investigator: Kitt Petersen, MD Yale University
  More Information

No publications provided

Responsible Party: Kitt Petersen, Professor of Internal Medicine, Yale University
ClinicalTrials.gov Identifier: NCT02193295     History of Changes
Other Study ID Numbers: 020290-20997
Study First Received: June 25, 2014
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Weight Reduction
Caloric Restriction
Euglycemic Hyperinsulinemic Clamp
Magnetic Resonance Spectroscopy

Additional relevant MeSH terms:
Weight Loss
Insulin Resistance
Body Weight Changes
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on September 16, 2014