Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity

Hypertriglyceridemia Clinical Trial

Official title:

Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05181514
• Other study ID #: Intralipid01
• Status: Completed
• Phase: N/A
• Start date: April 30, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: January 2022
• Source: Azienda Ospedaliero, Universitaria Pisana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Glucose Intolerance
• Hypertriglyceridemia
• Insulin Resistance

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa	PI

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Pisana

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Insulin sensitivity	Insulin sensitivity estimated by an OGTT-derived surrogate index (Matsuda index)	At the end of the 5-hour lipid infusion
Primary	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
Primary	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
Primary	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