Clinical trial NCT02342834: Effects of a Small Protein and Lipid Preload on Glucose Tolerance in Subjects With Impaired Glucose Homeostasis
Official title: Mechanisms Through Which a Small Protein and Lipid Preload Improves Glucose Tolerance in Subjects With Impaired Glucose Homeostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Azienda Ospedaliero, Universitaria Pisana
Sponsor class: OTHER
First posted: 2015-01-21
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* healthy, prediabetic or diet-controlled type 2 diabetic patients
* Subjects ≥ 18 and ≤65 years of age
* Lean, Overweight or Obese (BMI: 18 to 35 kg/m2)
* Normal liver and kidney function
* Normal thyroid function
* Read and understood the informed consent form and signed it voluntarily

Exclusion Criteria:

* Liver, heart, kidney, lung, infectious, neurological, psychiatric, immunological or neoplastic diseases.
* Type 1 or insulin treated diabetes.
* Pregnancy or lactation
* Illicit drug abuse or alcoholism
* Subject treated with insulin or treatment
* Subjects taking anoretic drugs
* Subjects on steroid treatment
* Subjects after bariatric surgery.

Primary outcomes:
measure: Plasma glucose response during the Oral Glucose Tolerance Test
timeFrame: 120 minutes
Secondary outcomes:
measure: Insulin secretion, estimated from C-peptide deconvolution
timeFrame: 120 minutes
measure: Insulin sensitivity, estimated from glucose and insulin levels during the Oral Glucose Tolerance Test with the use of Oral Glucose Insulin Sensitivity index
timeFrame: 120 minutes
measure: Insulin clearance, estimated by calculating the Insulin secretion/Plasma insulin ratio
timeFrame: 120 minutes
measure: 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
timeFrame: 120 minutes
measure: Incretin secretion (plasma GLP-1, plasma GIP)
timeFrame: 120 minutes
measure: Plasma glucagon
timeFrame: 120 minutes
measure: Plasma Non Esterified Fatty Acids
timeFrame: 120 minutes
measure: Beta cells function parameters (glucose sensitivity, rate sensitivity, potentiation factor ratio), calculated by modeling insulin secretion and glucose concentration.
timeFrame: 120 minutes
measure: Endothelial function assessed as the reactive hyperemia index by an EndoPAT device
timeFrame: fasting, 60 min and 120 min during the control and preload OGTT
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
state: PI
Study officials:
affiliation: Azienda Ospedaliero, Universitaria Pisana
name: Andrea Natali, Professor
role: STUDY_CHAIR
References:
citation: Trico D, Frascerra S, Baldi S, Mengozzi A, Nesti L, Mari A, Natali A. The insulinotropic effect of a high-protein nutrient preload is mediated by the increase of plasma amino acids in type 2 diabetes. Eur J Nutr. 2019 Sep;58(6):2253-2261. doi: 10.1007/s00394-018-1778-y. Epub 2018 Jul 14.
citation: Trico D, Baldi S, Tulipani A, Frascerra S, Macedo MP, Mari A, Ferrannini E, Natali A. Mechanisms through which a small protein and lipid preload improves glucose tolerance. Diabetologia. 2015 Nov;58(11):2503-12. doi: 10.1007/s00125-015-3710-9. Epub 2015 Jul 30.