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.
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
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
12
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.
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.
Azienda Ospedaliero-Universitaria Pisana
Pisa, PI, Italy
Glucose control
Incremental area under the curve (AUC) of plasma glucose in response to the oral glucose tolerance test (OGTT)
Time frame: 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)
Time frame: 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)
Time frame: At the end of the 5-hour lipid infusion
Insulin sensitivity
Insulin sensitivity estimated by an OGTT-derived surrogate index (Matsuda index)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At the end of the 5-hour lipid infusion
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