Abstract

Current approaches to insulin replacement in type 1 diabetes are unable to achieve optimal levels of glycemic control without substantial risk of hypoglycemia and substantial burden of self-management. Advances in biology and technology present beta cell replacement and automated insulin delivery as two alternative approaches. Here we discuss current and future prospects for the relative risks and benefits for biological and psychosocial outcomes from the perspective of researchers, clinicians, and persons living with diabetes. Beta cell replacement using pancreas or islet transplant can achieve insulin independence but requires immunosuppression. Although insulin independence may not be sustained, time in range of 80-90%, minimal glycemic variability and abolition of hypoglycemia is routine after islet transplantation. Clinical trials of potentially unlimited supply of stem cell-derived beta cells are showing promise. Automated insulin delivery (AID) systems can achieve 70-75% time in range, with reduced glycemic variability. Impatient with the pace of commercially available AID, users have developed their own algorithms which appear to be at least equivalent to systems developed within conventional regulatory frameworks. The importance of psychosocial factors and the preferences and values of persons living with diabetes are emerging as key elements on which therapies should be evaluated beyond their impact of biological outcomes. Biology or technology to deliver glucose dependent insulin secretion is associated with substantial improvements in glycemia and prevention of hypoglycemia while relieving much of the substantial burden of diabetes. Automated insulin delivery, currently, represents a more accessible bridge to a biologic cure that we expect future cellular therapies to deliver.

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