Effects of a Small Protein and Lipid Preload on Glucose Tolerance in Subjects With Impaired Glucose Homeostasis

Mechanisms Through Which a Small Protein and Lipid Preload Improves Glucose Tolerance in Subjects With Impaired Glucose Homeostasis

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Dietary supplement: Small mixed protein and lipid meal

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • PI
    • Pisa, PI, Italy, 56127
      • Azienda Ospedaliero-Universitaria Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; During the "control" study, each subject ingest 500 ml of water 30 minutes before a standard 75 g Oral Glucose Tolerance Test
Experimental: Small mixed protein and lipid meal; During the "preload" study, each subject ingest a small mixed meal 30 minutes before a standard 75 g Oral Glucose Tolerance Test. The meal is composed by 50 g of parmesan cheese, one small size boiled egg and 300 ml of water (250 kcal, 23 g protein, 17 g fat and 2 g of carbohydrate).	Dietary supplement: Small mixed protein and lipid meal; Ingestion of a small mixed protein and lipid meal 30 minutes before glucose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma glucose response during the Oral Glucose Tolerance Test	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin secretion, estimated from C-peptide deconvolution		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.	120 minutes
Insulin clearance, estimated by calculating the Insulin secretion/Plasma insulin ratio		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		120 minutes
Incretin secretion (plasma GLP-1, plasma GIP)		120 minutes
Plasma glucagon		120 minutes
Plasma Non Esterified Fatty Acids		120 minutes
Beta cells function parameters (glucose sensitivity, rate sensitivity, potentiation factor ratio), calculated by modeling insulin secretion and glucose concentration.		120 minutes
Endothelial function assessed as the reactive hyperemia index by an EndoPAT device		fasting, 60 min and 120 min during the control and preload OGTT

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana
• Investigators: Study Chair: Andrea Natali, Professor, Azienda Ospedaliero, Universitaria Pisana

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: LISBONA