Hypoglycemia, or abnormally low blood sugar (glucose), is often associated with exogenous insulin administration by diabetics. Glucose is the body's main source of energy and when its levels drop, individuals may experience symptoms ranging from confusion, irritability and dizziness to more severe complications such as seizures and unconsciousness.
Diabetics who use insulin therapy to control glucose levels can develop a complication called impaired awareness of hypoglycemia (IHA) in which the ability to recognize the onset of low blood sugar becomes diminished or absent resulting in severe hypoglycemia. These severe hypoglycemic events (SHE) can cause accidents, injuries, coma and death.
Northwestern Medicine researchers are co-investigators in a breakthrough clinical trial that found transplanted human islets prevent hypoglycemic events and provide excellent glycemic control for patients with Type 1 diabetes with severe hypoglycemia. The results of the multi-center, single arm, phase III study are published in Diabetes Care.
"Islet transplantation is heralding a new era of breakthrough therapies for Type 1 diabetes that isn't controlled by conventional treatments," said co-author Xunrong Luo, director of the Islet Cell Transplantation Program at Northwestern Memorial Hospital and Associate Professor of Medicine and Surgery at Northwestern University Feinberg School of Medicine. "These results make a clear case for islet transplantation as a viable treatment option for individuals with Type 1 diabetes complicated by severe hypoglycemia. Our research found that transplanted islet cells provided glycemic control, restored hypoglycemia awareness and protection from severe hypoglycemic events."
Investigators at eight sites in North America, including Northwestern Memorial, enrolled 48 adults who had Type 1 diabetes for more than five years. They found that nearly 88% of the 48 subjects who received islet transplants were free of severe hypoglycemic events, had restored hypoglycemia awareness and had excellent glycemic control at one year. Researchers also reported subjects had an insulin independence rate of 52% at year one. At year two, 71% of subjects were free of severe hypoglycemic events, had restored hypoglycemia awareness and excellent glycemic control. No study-related deaths or disabilities occurred, with five enrollees experiencing transplant-related complications and two had infections attributed to immunosuppression. Researchers will do prolonged follow up on the enrollees to determine the long-term outcomes of islet transplant for Type 1 diabetes.
In addition to demonstrating clinical efficacy of human islet transplantation, this trial has generated a standardized good manufacturing practice process for human islet manufacturing, and has defined product release criteria and testing methods that can be adhered to by multiple transplant sites. The manufacturing and clinical data generated by this study can now be cross-referenced by individual transplant centers for the purpose of filing a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for purified human pancreatic islets.
"The next step for this compelling research is to seek FDA approval for islet transplantation as a standard of care therapy for Type 1 diabetes," said Luo. "The success of this license-enabling study symbolizes the importance and power of team-science in the modern era of research. When scientists and institutions work together, we're more successful in developing new therapies and propelling medicine forward."