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

Abstract

Purpose of ReviewNew 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 FindingsMultiple 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.SummaryClosed 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.

Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement

“…Some randomized controlled trials proved that the artificial pancreas system could efficiently adjust the glycemic index by automatically delivering exogenous insulin with dosing algorithms based on sensor glucose levels (11). However, the lag time of glycemia detected by CGM and the risk of hypoglycemia and infections limit the application of artificial pancreas, and some of the patients with unawareness of hypoglycemic events such as brittle type T1DM are not qualified to use the artificial pancreas (12,13). Also, insulin replacement therapy can only supplement the missing insulin and cannot fundamentally restore the function of the pancreas.…”

The Role of Interleukin-1β in Destruction of Transplanted Islets

“…The development of stem cell–derived β cells such as human embryonic stem cells (hES) and induced pluripotent stem cells (iPSC)-derived insulin-producing cells is expected to offer the solutions. Although several teams have successfully manufactured insulin-secreting cells from hES and iPSC, clinical translation requires new solutions to solve the safety problems regarding teratoma formation and immune rejection 40 . Moreover, stem cell–derived β cells are “immature” that may be more vulnerable to inflammatory response such as IL-1β 41 .…”

Translational Research Symposium—collaborative efforts as driving forces of healthcare innovation

“…This could be overcome by the use of stem cell-derived beta cells and the use of immune-evasive delivery vehicles, which show great promise as a long-term solution [34]. However, their large scale implementation in the clinics is still far from becoming a reality for a number of factors, beyond just technical challenges, including, high average selling cost and long path to regulatory approval [35].…”

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