title: Characterizing the dynamic interaction among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese adults.
abstract: The effects of altered gastric emptying on glucose absorption and kinetics are not well understood in nondiabetic obese adults. The aim of this work was to develop a physiology-based model that can characterize and compare interactions among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese and lean healthy adults. Dynamic glucose, insulin, and gastric emptying (measured with breath test) data from 12 nondiabetic obese and 12 lean healthy adults were available until 180 min after an oral glucose tolerance test (OGTT) with 10, 25, and 75 g of glucose. A physiology-based model was developed to characterize glucose kinetics applying nonlinear mixed-effects modeling with NONMEM7.3. Glucose kinetics after OGTT was described by a one-compartment model with an effect compartment to describe delayed insulin effects on glucose clearance. After the interactions between individual gastric emptying and glucose absorption profiles were accounted for, the glucose absorption rate was found to be similar in nondiabetic obese and lean controls. Baseline glucose concentration was estimated to be only marginally higher in nondiabetic obese subjects (4.9 vs. 5.2 mmol/l), whereas insulin-dependent glucose clearance in nondiabetic obese subjects was found to be cut in half compared with lean controls (0.052 vs. 0.029 l/min) and the insulin concentration associated with 50% of insulin-dependent glucose elimination rate was approximately twofold higher in nondiabetic obese subjects compared with lean controls (7.1 vs. 15.3 μU/ml). Physiology-based models can characterize and compare the dynamic interaction among gastric emptying, glucose absorption and glycemic control in populations of interest such as lean healthy and nondiabetic obese adults.
authors.affiliation: Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland; melanie.wilbaux@ukbb.ch.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Wilbaux
authors.affiliation: Department of Biomedicine, Division of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland; and.
authors.forename: Bettina K
authors.initials: BK
authors.lastname: Wölnerhanssen
authors.affiliation: Department of Biomedicine, Division of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland; and.
authors.forename: Anne Christin
authors.initials: AC
authors.lastname: Meyer-Gerspach
authors.affiliation: Department of Biomedicine, Division of Gastroenterology and Hepatology, University Hospital of Basel, Basel, Switzerland; and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.affiliation: Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.|Quantitative Solutions LP, Menlo Park, Calfornia.
authors.forename: Marc
authors.initials: M
authors.lastname: Pfister
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D065570:Gastric Absorption; D005746:Gastric Emptying; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology*; D011236:Prediabetic State / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: NONMEM; gastric emptying; glucose absorption; glycemic control; obese adults