Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity

The investigators aim to evaluate whether and to what extent glucose tolerance, beta cell function, insulin clearance, and glucose metabolic fluxes change in response to an acute increase in plasma triglycerides during lipid infusion, independently of free fatty acid (FFA) levels, in nondiabetic subjects.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance; Hypertriglyceridemia
• Intervention / Treatment: Other: Normal Saline; Other: 20% Intralipid

Detailed Description

Mild hypertriglyceridemia is associated with reduced glucose tolerance and increased risk of type 2 diabetes, independent of obesity, in both cross-sectional and prospective studies. It is unclear whether this association is direct or mediated by circulating lipid substrates of triglycerides (free fatty acids, or FFA) and which are the mechanisms involved.

To comprehensively examine the effects of mild acute hypertriglyceridemia on major glucose homeostatic mechanisms involved in diabetes progression, two dual-labeled oral glucose tolerance tests (OGTT) during 5-hour intravenous infusions of either 20% Intralipid or normal saline will be performed in healthy lean volunteers. Lipid-induced changes in glucose tolerance and insulin metabolism will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • PI
    • Pisa, PI, Italy, 56127
      • Azienda Ospedaliero-Universitaria Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-65 years
• Body mass index (BMI) 18-35 kg/m2
• both women and men

Exclusion Criteria:

• chronic or acute diseases
• any medications
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Normal Saline; Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of normal saline	Other: Normal Saline; Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of normal saline (Sodium Chloride 0.9%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-[2H2]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of [U-13C] glucose.
EXPERIMENTAL: 20% Intralipid; Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of Intralipid 20%.	Other: 20% Intralipid; Participants will receive a 5 h primed (375 mL/m2)-continuous (25 mL h-1 m-2) i.v. infusion of 20% fat emulsion (Intralipid 20%), together with a 5 h primed (28 µmol/kg)-continuous (0.28 µmol min-1 kg-1) infusion of 6,6-[2H2]glucose. After 2 h, participants will consume within 5 min an oral glucose drink consisting of 147 mL of 50% dextrose solution (wt/vol) enriched with 1.5 g of [U-13C] glucose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose control	Incremental area under the curve (AUC) of plasma glucose in response to the oral glucose tolerance test (OGTT)	At the end of the 5-hour lipid infusion
Insulin secretion	Insulin secretion rate (ISR) estimated from C-peptide deconvolution at fasting and in response to the oral glucose tolerance test (OGTT)	At the end of the 5-hour lipid infusion
Beta cell glucose sensitivity	Beta cell glucose sensitivity calculated by mathematical modeling of insulin secretion rate (ISR) and plasma glucose concentrations during the oral glucose tolerance test (OGTT)	At the end of the 5-hour lipid infusion
Insulin sensitivity	Insulin sensitivity estimated by an OGTT-derived surrogate index (Matsuda index)	At the end of the 5-hour lipid infusion
Insulin clearance	Insulin clearance calculated as the ratio between insulin secretion rate (ISR) and plasma insulin levels	At the end of the 5-hour lipid infusion
Rate of oral glucose appearance (RaO)	The rate of oral glucose appearance (RaO) will be assessed from the time course of the plasma tracer/tracee ratio of 6,6-[2H2]glucose and [U-13C]glucose	At the end of the 5-hour lipid infusion
Endogenous glucose production (EGP)	The endogenous glucose production (EGP) will be assessed from the time course of the plasma tracer/tracee ratio of 6,6-[2H2]glucose and [U-13C]glucose	At the end of the 5-hour lipid infusion

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 30, 2019
• Primary Completion (ACTUAL): December 1, 2021
• Study Completion (ACTUAL): December 1, 2021

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: January 4, 2022
• First Posted (ACTUAL): January 6, 2022

Study Record Updates

• Last Update Posted (ACTUAL): January 6, 2022
• Last Update Submitted That Met QC Criteria: January 4, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hyperglycemia; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Glucose Intolerance; Insulin Resistance; Hypertriglyceridemia; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: Intralipid01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No