Low Dose Fat-Induced Insulin Resistance

Last updated: April 12, 2026
Sponsor: University of Pennsylvania
Overall Status: Completed

Phase

1

Condition

Hormone Deficiencies

Diabetes (Pediatric)

Diabetes Prevention

Treatment

Intralipid, 20% Intravenous Emulsion

Clinical Study ID

NCT03479671
831425
  • Ages 18-44
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

The primary goal of this study is to determine the dose of fatty acids that acutely induces mild insulin resistance in healthy volunteers. We hypothesize that a low-dose of fatty acid infusion (Intralipid/heparin) will cause a mild insulin resistance. The dose of fatty acid infusion that reliably causes mild insulin resistance will be selected for use in future studies.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Subjects who are able to provide written informed consent and to comply with theprocedures of the study protocol

Exclusion

Exclusion Criteria:

  • History of diabetes

  • History of diabetes in more than one first-degree relative

  • Body mass index (BMI) <19 or >27 kg/m2

  • HbA1c >5.7%

  • Blood Pressure: systolic >160 mmHg or diastolic > 100 mmHg

  • Baseline hemoglobin concentration < 11 g/dl in women and < 12 g/dl in men

  • Estimated glomerular filtration rate < 55 ml/min/1.73 m2 (calculated using thesubject's measured serum creatinine and the Modification of Diet in Renal Disease [MDRD] study estimation formula).

  • Presence of soy or egg allergies (due to possible reactions with fat infusate)

  • For female participants: Positive pregnancy test, presently breast-feeding, orunwillingness to use effective contraceptive measures for the duration of the study.Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicideare acceptable contraceptive methods; condoms used alone are not acceptable.

  • Known active alcohol or substance abuse

  • Use of tobacco within the previous year

  • Severe co-existing cardiac disease, characterized by any one of these conditions:

  1. history of myocardial infarction within past 6 months;

  2. history of ischemia on functional cardiac exam within the last year;

  3. history of left ventricular ejection fraction < 30%.

  • Persistent elevation of liver function tests > 1.5 times normal upper limits

  • Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/orfasting triglycerides > 200 mg/dl)

  • Receiving treatment for a medical condition requiring chronic use of systemicsteroids, except for the use of ≤ 5 mg prednisone daily, or an equivalentphysiological dose of hydrocortisone

  • Presence of a seizure disorder

  • Use of any investigational agents within 4 weeks of enrollment

  • Any medical condition, which in the opinion of the investigator, will interfere withthe safe completion of the study

  • History of pancreatitis

  • Presence of a metal allergy (aluminum)

Study Design

Total Participants: 9
Treatment Group(s): 1
Primary Treatment: Intralipid, 20% Intravenous Emulsion
Phase: 1
Study Start date:
January 01, 2020
Estimated Completion Date:
November 19, 2024

Study Description

This study is designed to test the hypothesis that a low-dose of fatty acid infusion (Intralipid/heparin) will cause mild insulin resistance. This dose-finding study is critical for future studies on free-fatty acid induced insulin resistance.

Healthy male and healthy female volunteers will undergo a 6 hour hyperinsulinemic-euglycemic clamp, in order to establish insulin sensitivity parameters in the presence of fatty acid co-infusion. The subjects will then return 1-3 weeks later, and undergo another 6 hour HIE clamp, this time in the presence of low-dose fatty acid co-infusion (30ml/hr). If this dose does not achieve ~25% reduction in the rate of glucose disposal, then the dose-confirmation study will be repeated 1-3 weeks later with a medium-dose fatty acid co-infusion (60ml/hr).

A dose-response effect of fatty acids on insulin resistance has been demonstrated before, but not in the precise conditions of our study. This dose-finding study is critical because future studies require a reliable dose of fatty acid infusion, and the exact dose of fatty acid infusion that causes mild insulin resistance may be different in the conditions of our study.

Connect with a study center

  • University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • University of Pennsylvania

    Philadelphia 4560349, Pennsylvania 6254927 19104
    United States

    Site Not Available

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