Exercise Effect on Insulin-Dependent and Insulin-Independent Glucose Utilization in Healthy and Type 1 Diabetes Individuals. A Modeling Study.

Exercise effects (EE) on whole body glucose rate of disappearance (Rd) occur through insulin- independent (IIRd) and insulin-dependent (IDRd) mechanisms. Quantifying these processes in vivo would allow a better understanding of the physiology of glucose regulation. This is of particular importance in individuals with type 1 diabetes (T1D) since such a knowledge may help to improve glucose management. However, such a model is still lacking. Here, we analyzed data from 6 T1D and 6 nondiabetic (ND) subjects undergoing a labeled glucose clamp study during, before and after a 60 min exercise session at 65% VO2max on three randomized visits: euglycemia-low insulin, euglycemia-high insulin and hyperglycemia-low insulin. We tested a set of models, all sharing a single-compartment description of glucose kinetics, but differing in how exercise is assumed to modulate glucose disposal. Model selection was based on parsimony criteria. The best model assumed an exercise-induced immediate effect on IIRd and a delayed effect on IDRd. It predicted that exercise increases IIRd, compared to rest, by 66% - 82% and 67% - 97% in T1D and ND, respectively, not significantly different between the two groups. Conversely, the exercise effect on IDRd ranged between 81% - 155% in T1D and it was significantly higher than ND, which ranged between 10% - 40%. The exaggerated effect observed in IDRd can explain the higher hypoglycemia risk related to T1D individuals. This novel exercise model could help in informing safe and effective glucose management during and after exercise in T1D individuals.