Artificial Pancreas or Novel Beta-Cell Replacement Therapies: a Race for Optimal Glycemic Control?

Abstract

Purpose of review: New treatment strategies are needed for patients with type 1 diabetes (T1D). Closed loop insulin delivery and beta-cell replacement therapy are promising new strategies. This review aims to give an insight in the most relevant literature on this topic and to compare the two radically different treatment modalities.

Recent findings: Multiple clinical studies have been performed with closed loop insulin delivery devices and have shown an improvement in overall glycemic control and time spent in hypoglycemia. Beta-cell transplantation has been shown to normalize or greatly improve glycemic control in T1D, but the donor organ shortage and the necessity to use immunosuppressive agents are major drawbacks. Donor organ shortage may be solved by the utilization of stem cell-derived beta cells, which has shown great promise in animal models and are now tested in clinical studies. Immunosuppression may be avoided by encapsulation. Closed loop insulin delivery devices are promising treatment strategies and are likely to be used in clinical practice in the short term. But this approach will always suffer from delays in glucose measurement and insulin action preventing it from normalizing glycemic control. In the long term, stem cell-derived beta cell transplantation may be able to achieve this, but wide implementation in clinical practice is still far away.

Keywords: Bionic pancreas; Diabetes mellitus; Stem cells.

Fig. 1

Challenges in obtaining optimal “real-time” glycemic control in artificial pancreas and encapsulated beta-cell replacement strategies. Left panel: in native pancreatic islets or transplanted islets in the liver that have been vascularized, the insulin-producing beta cells are in close proximity to the islet capillary network. Nutrients, in particular carbohydrates (blue dots), are rapidly sensed by the insulin-producing cells. Based on nutrient levels, the cells are able to immediately secrete the appropriate amount of insulin (black dots) into the islet capillaries. Middle panel: cell clusters containing insulin-producing cells (islets, beta-like cells derived from pluripotent stem cells) that are loaded into (macro)encapsulation devices before implantation in a recipient. There is no direct contact between the insulin-producing cells and capillaries. This “dead space” and limitations in transport of molecules across the macrocapsule membrane cause delayed (blood) glucose sensing and delayed insulin action. Right panel: in current artificial pancreases, there is a glucose sensor in the skin which is coupled to a transmitter that sends information about glucose concentrations to a receiver. This receiver feeds the information in a control algorithm that controls insulin delivery through an infusion set. There is a variable delay in blood glucose reporting, using interstitial glucose monitoring by a subcutaneous glucose sensor. This can also be termed “delayed (blood) glucose sensing.” There is also a delay between subcutaneous insulin administration and resorption of insulin into the blood stream causing delayed insulin action