title: Mechanisms through which a small protein and lipid preload improves glucose tolerance.
abstract: OBJECTIVE
  Small protein or lipid preloads are able to improve glucose tolerance to a different extent and through different and poorly defined mechanisms. We aimed at quantifying the effect of a mixed protein and lipid preload and at evaluating the underlying mechanisms.
  
  
  METHODS
  Volunteers with normal (NGT, n = 12) or impaired (IGT, n = 13) glucose tolerance and patients with type 2 diabetes (n = 10) underwent two OGTTs coupled to the double glucose tracer protocol, preceded by either 50 g of parmesan cheese, a boiled egg and 300 ml of water, or 500 ml of water. We measured plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP), NEFA and glucose tracers, and calculated glucose fluxes, beta cell function variables, insulin sensitivity and clearance.
  
  
  RESULTS
  After the nutrient preload, the OGTT-induced rise of plasma glucose was lower than after water alone in each study group. This reduction—more pronounced across classes of glucose tolerance (NGT -32%, IGT -37%, type 2 diabetes -49%; p < 0.002)—was the result of different combinations of slower exogenous glucose rate of appearance, improved beta cell function and reduced insulin clearance, in this order of relevance, which were associated with an only mild stimulation of GIP and GLP-1.
  
  
  CONCLUSIONS
  After a non-glucidic nutrient preload, glucose tolerance improved in proportion to the degree of its baseline deterioration through mechanisms that appear particularly effective in type 2 diabetes. Exploiting the physiological responses to nutrient ingestion might reveal, at least in the first stages of the diabetic disease, a potent tool to improve daily life glycaemic control.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02342834 FUNDING: This work was supported by grants from the University of Pisa (Fondi di Ateneo) and by FCT grant (PIC/IC/82956/2007).
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy. domenico.trico@for.unipi.it.|Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy. domenico.trico@for.unipi.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tricò
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Baldi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tulipani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Frascerra
authors.affiliation: CEDOC, NOVA Medical School/Faculdade de Ciencias Medicas (NMS/FCM), Universidade Nova de Lisboa, Lisboa, Portugal.|APDP-Diabetes Portugal, Education and Research Centre (APDP-ERC), Lisboa, Portugal.
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Macedo
authors.affiliation: National Research Council, Institute of Neuroscience, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy.|National Research Council, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 57, Pisa, 56100, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Natali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004041:Dietary Fats; D004044:Dietary Proteins; D007328:Insulin; D052216:Glucagon-Like Peptide 1
keywords: Beta cell function; Glucose absorption; Glucose intolerance; Hepatic glucose production; Insulin secretion in vivo; Insulin sensitivity; Lipid; Protein; Type 2 diabetes