Management of Hypoglycemic Unawareness and the Current Status of Clinical Allogeneic Islet Transplantation

Abstract

Problematic hypoglycemia is defined as a condition in which episodes of severe hypoglycemia are unpredictable and/or cannot be easily explained or prevented, typically associated with impaired awareness of hypoglycemia. The treatment algorithm for patients with type 1 diabetes and problematic hypoglycemia emphasizes the stepwise approach including structured education regarding multiple daily injections of insulin, use of technology such as sensor-augmented pump with low glucose suspension, and islet or pancreas transplantation. Although the prevalence of insulin independence at 5 years is 25~50% in most recent clinical trials of islet transplantation, both islet and pancreas transplantation are equally efficient to cure severe hypoglycemia for more than 5 years in about 70% of the recipients. To date, international cohorts of clinical islet transplantation such as the French-Swiss GRAGIL Network have successfully reproduced the long-term C-peptide positivity initially achieved with the Edmonton protocol, with long-term insulin independence demonstrated in selected cases. Several cases with partial islet graft function have been reported in Korea, with the first case of long-term insulin independence being reported in late 2015. Therefore, islet transplantation can offer freedom from life-threatening severe hypoglycemia for type 1 diabetes patients with problematic hypoglycemia, even in non-responders to the latest technology-based treatment.