The purpose of this study is: * to measure the size of the effect on glucose tolerance of a small mixed protein and lipid meal given as a pre-load in individuals with different glucose tolerance status * to investigate the underlying mechanisms by accurately evaluating beta cell function, insulin sensitivity, insulin clearance and glucose kinetics (oral absorption, endogenous production, rate of utilization) together with gut hormones plasma concentration.
As supported by experimental and clinical data, oral carbohydrate tolerance is influenced by the coingestion of nutrients through multiple mechanisms. The ingestion itself, the contact with the gastric mucosa, the arrival into the intestine and the subsequent digestion are known to produce neural reflexes, hormonal responses and plasma substrates gradients which, by modulating gastric emptying, insulin secretion and insulin clearance participate in the regulation of postprandial glycaemia. The size of this effect is influenced by a number of factors: the specific nutrient chemical characteristics (fat vs protein and composition) and their physical properties (solid vs liquid), the timing (pre-load vs coingestion) and finally the individual glucose tolerance status. To our knowledge, the effect on glucose excursions of a combination of protein and fat given before carbohydrate is still unknown and also unknown is the contribution of different mechanisms involved in the control of glucose homeostasis in subjects with different degrees of glucose tolerance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
35
Ingestion of a small mixed protein and lipid meal 30 minutes before glucose
Azienda Ospedaliero-Universitaria Pisana
Pisa, PI, Italy
Plasma glucose response during the Oral Glucose Tolerance Test
Time frame: 120 minutes
Insulin secretion, estimated from C-peptide deconvolution
Time frame: 120 minutes
Insulin sensitivity, estimated from glucose and insulin levels during the Oral Glucose Tolerance Test with the use of Oral Glucose Insulin Sensitivity index
The Oral Glucose Insulin Sensitivity index (OGIS; equation for a 2-h oral glucose test with a glucose dose of 75 g) is the mean glucose clearance change (basal vs OGTT 60-120 min), divided by the mean plasma insulin concentration gradient over the same time interval.
Time frame: 120 minutes
Insulin clearance, estimated by calculating the Insulin secretion/Plasma insulin ratio
Time frame: 120 minutes
Glucose fluxes (intestinal glucose absorption, endogenous glucose production, rate of disappearance of plasma glucose), assessed by modeling glucose tracers enrichments using a standard double tracers technique
Time frame: 120 minutes
Incretin secretion (plasma GLP-1, plasma GIP)
Time frame: 120 minutes
Plasma glucagon
Time frame: 120 minutes
Plasma Non Esterified Fatty Acids
Time frame: 120 minutes
Beta cells function parameters (glucose sensitivity, rate sensitivity, potentiation factor ratio), calculated by modeling insulin secretion and glucose concentration.
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Time frame: 120 minutes
Endothelial function assessed as the reactive hyperemia index by an EndoPAT device
Time frame: fasting, 60 min and 120 min during the control and preload OGTT