Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity

Not Applicable

Completed

• Conditions: Glucose Intolerance; Hypertriglyceridemia
• Interventions: Other: Normal Saline; Other: 20% Intralipid

• Registration Number: NCT05181514
• Lead Sponsor: Azienda Ospedaliero, Universitaria Pisana

Brief 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.

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 Timeline

• Study Start: 2019-04-30
• Primary Completion: 2021-12-01
• Study Completion: 2021-12-01
• Study First Submitted: 2021-12-06
• Status Verified: 2022-01
• Study First Submitted QC: 2022-01-04
• Last Update Submitted: 2022-01-04
• Study First Posted: 2022-01-06
• Last Update Posted: 2022-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Normal Saline	Normal Saline	Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of normal saline
20% Intralipid	20% Intralipid	Participants will undergo a dual labeled, 3-h oral glucose tolerance test (OGTT) during i.v. infusion of Intralipid 20%.

Primary Outcome Measures

Name	Time	Method
Glucose control	At the end of the 5-hour lipid infusion	Incremental area under the curve (AUC) of plasma glucose in response to the oral glucose tolerance test (OGTT)
Beta cell glucose sensitivity	At the end of the 5-hour lipid infusion	Beta cell glucose sensitivity calculated by mathematical modeling of insulin secretion rate (ISR) and plasma glucose concentrations during the oral glucose tolerance test (OGTT)
Insulin clearance	At the end of the 5-hour lipid infusion	Insulin clearance calculated as the ratio between insulin secretion rate (ISR) and plasma insulin levels
Rate of oral glucose appearance (RaO)	At the end of the 5-hour lipid infusion	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
Endogenous glucose production (EGP)	At the end of the 5-hour lipid infusion	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
Insulin sensitivity	At the end of the 5-hour lipid infusion	Insulin sensitivity estimated by an OGTT-derived surrogate index (Matsuda index)
Insulin secretion	At the end of the 5-hour lipid infusion	Insulin secretion rate (ISR) estimated from C-peptide deconvolution at fasting and in response to the oral glucose tolerance test (OGTT)

Trial Locations

Locations (1)

Azienda Ospedaliero-Universitaria Pisana; 🇮🇹 Pisa, PI, Italy