Reversal of Lipid-Induced Insulin Resistance

NCT02193295 | Recruiting

• 2 other identifiers: 02029020997_aR01DK135645
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

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. Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).

Conditions

Insulin Resistance; NAFLD

Keywords

Weight Reduction; Caloric Restriction; Euglycemic Hyperinsulinemic Clamp; Magnetic Resonance Spectroscopy; PINTA

Outcome Measures

Primary Outcomes (1)

• Improvements in insulin sensitivity

  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.

  up to 6 months intervention to examine whether insulin sensitivity has improved significantly after the moderate weight reduction

Study Arms (2)

Lifestyle Intervention

EXPERIMENTAL

Caloric Restriction to reverse lipid-induced insulin resistance.

Behavioral: Caloric Restriction

Baseline Assessment of Hepatic Mitochondrial Fat Oxidation

EXPERIMENTAL

Tracer study to assess hepatic mitochondrial fat oxidation (PINTA).

Behavioral: Caloric Restriction

Interventions

Caloric Restriction BEHAVIORAL

Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss. Weekly visits for measurements of body weight, body composition, blood glucose and MRS measurements of liver and muscle lipid.

Also known as: Dietary intervention to reduce lipid content in liver and muscle with minimal overall weight loss.

Baseline Assessment of Hepatic Mitochondrial Fat Oxidation; Lifestyle Intervention

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Lactose intolerance Any blood count, clotting abnormalities HYpertriglyceridemeia (TG over 100 mg/dL)
• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Magnetic Resonance Research Center (MRRC)

New Haven, Connecticut, 06511, United States

ENROLLING BY INVITATION

Yale Center for Clinical Investigation HRU

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Insulin Resistance; Non-alcoholic Fatty Liver Disease; Weight Loss; Pinta

Interventions

Caloric Restriction; Liver Extracts

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Tissue Extracts; Complex Mixtures

Study Officials

• Kitt Petersen, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kitt Petersen, MD

CONTACT

203-785-5447; kitt.petersen@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 17, 2014
• Study Start: October 1, 2002
• Primary Completion (Estimated): October 1, 2034
• Study Completion (Estimated): December 1, 2034
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)