Effects of altered gastric emptying on glucose absorption and kinetics are not well understood in non-diabetic 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 non-diabetic obese and lean healthy adults. Dynamic glucose, insulin and gastric emptying (measured with breath test) data from 12 non-diabetic obese and 12 lean healthy adults were available until 180 minutes after an oral glucose tolerance test (OGTT) with 10g, 25g and 75g of glucose. A physiology-based model was developed to characterize glucose kinetics applying nonlinear mixed-effects modelling 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 accounting for interactions between individual gastric emptying and glucose absorption profiles the glucose absorption rate was found to be similar in non-diabetic obese and lean controls. Baseline glucose concentration was estimated to be only marginally higher in non-diabetic obese subjects (4.9 versus 5.2 mmol.L-1), whereas insulin-dependent glucose clearance in non-diabetic obese subjects was found to be cut in half compared to lean controls (0.052 versus 0.029 L.min-1) and insulin concentration associated with 50% of insulin-dependent glucose elimination rate was ~2-fold higher in non-diabetic obese subjects compared to lean controls (7.1 versus 15.3 μU.mL-1). 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 non-diabetic obese adults.
- Glucose absorption
- Gastric emptying
- Glycemic control
- Obese adults
- Copyright © 2016, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology