Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids

NCT03818178 | Recruiting

• 2 other identifiers: 18-0025205R01DK045343-27
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for muscle insulin resistance, although it has been shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours. The investigators do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid infusion (both compared to saline control). The investigators will compare the muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates, providing the first measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the whole body and cellular/molecular levels. By identifying which steps in the insulin signaling pathway are most affected, the investigators will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance. Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into intra-myocellular ceramides and abnormal insulin signaling. Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into intra-myocellular saturated DG and abnormal insulin signaling.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Change in fatty acid enrichment of intramyocellular signaling molecules before and after a euglycemic, hyperinsulinemic clamp

  The study involves the use of a hyperinsulinemic, euglycemic clamp to compare fatty acid enrichments in intramyocellular signaling molecules. The first half of the study will be the "pre-clamp" stage. During this stage, volunteers will receive an intravenous infusion of C13-labelled palmitate as a tracer in order for enrichment calculations to be performed pre-clamp. One muscle biopsy will be obtained to measure fatty acid enrichment within intramyocellular ceramides, diacylglycerols, long-chain acylcarnitines, and intramyocellular triglycerides. The insulin clamp will then commence, and volunteers will simultaneously receive an intravenous infusion of a second tracer, D-9 palmitate. This tracer will allow us to calculate enrichments during the insulin clamp stage of the study. A second muscle biopsy will be performed at the end of the insulin clamp, and similar enrichment calculations will be performed.

  18 hours

Study Arms (3)

Intralipid

EXPERIMENTAL

Dietary Supplement: Intralipid

Palm Oil

EXPERIMENTAL

Dietary Supplement: Palm Oil Emulsion

Saline

PLACEBO COMPARATOR

Other: Saline

Interventions

Palm Oil Emulsion DIETARY_SUPPLEMENT

Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.

Palm Oil

Saline OTHER

All participants will serve as their own controls with a saline infusion study day.

Saline

Intralipid DIETARY_SUPPLEMENT

Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.

Intralipid

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women and Men (Women premenopausal)
• BMI 18-27
• Weight stable
• Not pregnant/nursing

You may not qualify if:

• Ischemic heart disease
• Atherosclerotic valvular disease
• Smokers (\> 20 cigarettes per week)
• Bilateral oophorectomy
• Concomitant use of medications that can alter serum lipid profile (high dose fish oil, statins, niacin, fibrates, thiazolinediones, beta-blockers, atypical antipsychotics)
• Lidocaine allergy

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Insulin Resistance

Interventions

soybean oil, phospholipid emulsion; Sodium Chloride

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Michael D Jensen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pamela Reich

CONTACT

507-255-6062; Reich.Pamela@mayo.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 20, 2019
• First Posted: January 28, 2019
• Study Start: December 1, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)