Modeling the acute effects of exercise on insulin kinetics in type 1 diabetes.

ABSTRACT

Our objective is to develop a physiology-based model of insulin kinetics to understand how exercise alters insulin concentrations in those with type 1 diabetes (T1D). We reveal the relationship between the insulin absorption rate ([Formula see text]) from subcutaneous tissue, the insulin delivery rate ([Formula see text]) to skeletal muscle, and two physiological parameters that characterize the tissue the perfusion rate (Q) and the capillary permeability surface area (PS), both of which increase during exercise because of capillary recruitment. We compare model predictions to experimental observations from two pump-wearing T1D cohorts [resting subjects ([Formula see text]) and exercising subjects ([Formula see text])] who were each given a mixed-meal tolerance test and a bolus of insulin. Using independently measured values of Q and PS from literature, the model predicts that during exercise insulin concentration increases by 30% in plasma and by 60% in skeletal muscle. Predictions reasonably agree with experimental observations from the two cohorts, without the need for parameter estimation by curve fitting. The insulin kinetics model suggests that the increase in surface area associated with exercise-induced capillary recruitment significantly increases [Formula see text] and [Formula see text], which explains why insulin concentrations in plasma and skeletal muscle increase during exercise, ultimately enhancing insulin-dependent glucose uptake. Preventing hypoglycemia is of paramount importance in determining the proper insulin dose during exercise. The presented model provides mechanistic insight into how exercise affects insulin kinetics, which could be useful in guiding the design of decision support systems and artificial pancreas control algorithms.