Low Dose Fat-Induced Insulin Resistance (BCAA)

A Dose Finding Study for Fat-Induced Insulin Resistance in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance; Insulin Sensitivity
• Intervention / Treatment: Drug: Intralipid, 20% Intravenous Emulsion

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

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 the subject'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, or unwillingness to use effective contraceptive measures for the duration of the study. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are 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/or fasting triglycerides > 200 mg/dl)
• Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent physiological 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 with the safe completion of the study
• History of pancreatitis
• Presence of a metal allergy (aluminum)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Saline; Insulin sensitivity (rate of glucose disposal)
Experimental: Low Dose Fatty Acids; Insulin sensitivity (rate of glucose disposal) in response to 30 ml/hr fatty acid infusion	Drug: Intralipid, 20% Intravenous Emulsion; Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)
Experimental: Medium Dose Fatty Acids; Insulin sensitivity (rate of glucose disposal) in response to 60 ml/hr fatty acid infusion	Drug: Intralipid, 20% Intravenous Emulsion; Fatty Acid Infusion, either in low-dose (30 ml/hr) or medium-dose (60 ml/hr)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	Rate of Glucose Disposal (mg/kg/min)	6 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Zoltan P Arany, MD, PhD, Associate Professor of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): November 19, 2024

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Insulin Resistance; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; soybean oil, phospholipid emulsion
• Other Study ID Numbers: 831425

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No