title: Altered homeostatic adaptation of first- and second-phase beta-cell secretion in the offspring of patients with type 2 diabetes: studies with a minimal model to assess beta-cell function.
abstract: We adapted a minimal model to assess beta-cell function during a hyperglycemic glucose clamp and to uncover peculiar aspects of the relationship among beta-cell function, plasma glucose, and insulin sensitivity (IS) in offspring of Caucasian patients with type 2 diabetes (OfT2D). We pooled two data sets of OfT2D (n = 69) and control subjects (n = 45) with normal glucose regulation. Plasma C-peptide was measured during a hyperglycemic clamp ( approximately 10 mmol/l) to quantify model-based first-phase secretion and glucose sensitivity of second-phase secretion (beta). IS was quantified during the hyperglycemic clamp. In the pooled data, first-phase secretion was linearly and negatively related to fasting plasma glucose, but not IS; OfT2D lay on a distinct line shifted to the left of the control subjects. In contrast, beta was negatively related to IS, and OfT2D lay on a distinct line shifted more and more to the left of the control subjects, as IS was worse. Thus, in OfT2D lower beta-cell adaptive responses exist between ambient glycemia and first-phase insulin secretion and between IS and second-phase secretion. Under conditions leading to decreased insulin sensitivity, these disturbed relationships may lead to progression to diabetes in OfT2D.
authors.affiliation: Division of Endocrinology and Metabolic Diseases, University of Verona and Azienda Ospedaliera di Verona, Italy. rcbonado@tin.it
authors.forename: Riccardo C
authors.initials: RC
authors.lastname: Bonadonna
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Michele
authors.initials: M
authors.lastname: Muggeo
authors.forename: Hans
authors.initials: H
authors.lastname: Häring
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Timon W
authors.initials: TW
authors.lastname: van Haeften
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009679:Nuclear Family; D019518:Postprandial Period; D012016:Reference Values; D044465:White People
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin