Modeling Impulsive Injections of Insulin: Towards Artificial Pancreas

We propose two novel mathematical models with impulsive injection of insulin or its analogues for type 1 and type 2 diabetes mellitus. One model incorporates the periodic impulsive injection of insulin. We analytically show the existence and uniqueness of a positive globally asymptotically stable periodic solution for type 1 diabetes, which implies that the perturbation caused by insulin injection will not disturb homeostasis but amend the glucose from a pathological level toward a healthier level. We also show that the system is uniformly permanent for type 2 diabetes, that is, the glucose concentration level is uniformly bounded above and below. The other model determines the insulin injection by closely monitoring the glucose level when it reaches or passes a predefined but adjustable threshold value. We analytically prove the existence and stability of the order one periodic solution, which ensures that the perturbation by the injection in such an automated way can keep the blood glucose concentration under control. Our numerical analysis confirms and further enhances the usefulness and robustness of our models. The first model has clinical implications in that the glucose level of a diabetic can be controlled within a desired level by adjusting the values of two model parameters, injection period and injection dose. A method for choosing these two parameters is described. The second model is, to the best of our knowledge, the first attempt to conquer some critical issues in the design of an artificial pancreas with closed-loop approach. For the former case, our numerical analysis reveals that a regime with a smaller insulin dose and more frequent deliveries is more efficient and effective, but surprisingly, for the latter case, a larger dose is more effective. This can be significant in the design and development of the insulin pump and artificial pancreas.