title: Insulin release in impaired glucose tolerance: oral minimal model predicts normal sensitivity to glucose but defective response times.
abstract: The availability of quantitative indexes describing beta-cell function in normal life conditions is important for the characterization of impaired mechanisms of insulin secretion in pathophysiological states. Recently, an oral C-peptide minimal model has been proposed and applied to subjects with normal glucose tolerance (NGT) during graded up-and-down glucose infusion protocols (40-min periods at 4, 8, 16, 8, 4, and 0 mg.kg(-1).min(-1)) and oral glucose tolerance tests. These tests are characterized by slow glucose and C-peptide dynamics, which reproduce prandial conditions. In view of the importance of beta-cell dysfunction in the pathogenesis of type 2 diabetes, our aim was to test and use the oral minimal model in subjects with impaired glucose tolerance (IGT) to identify deranged mechanisms of beta-cell function. Plasma C-peptide and glucose data from graded up-and-down glucose infusions were analyzed in nine NGT and four IGT subjects using the classic deconvolution approach and the oral minimal model, and indexes of beta-cell function were derived. An index of insulin sensitivity was also obtained for each subject from minimal model analysis of glucose and insulin levels achieved during the test. Both deconvolution and minimal model analyses revealed that individuals with IGT have a relative defect in the ability to secrete enough insulin to adequately compensate for insulin resistance. Additionally, minimal model analysis suggests that insulin secretory defect in IGT arises from delays in the timing of the beta-cell response to glucose.
authors.affiliation: Department of Electronics and Informatics, University of Padua, Padua, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Breda
authors.forename: Gianna
authors.initials: G
authors.lastname: Toffolo
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Polonsky
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D011930:Reaction Time
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin