Islet Transplantation Restores Blood Sugar Awareness and Control in Type 1 Diabetes
NIH-funded study lays groundwork for potential application submission to FDA for licensure of islet preparation.
Hypoglycemia, or low blood sugar, typically is accompanied by symptoms such as tremors, sweating and heart palpitations that prompt people to eat or drink to raise their blood sugar levels. Those who do not experience these early warning signs — a condition called impaired awareness of hypoglycemia — are at increased risk for severe hypoglycemic events, during which the person is unable to treat himself or herself. Treatments such as behavioral therapies or continuous glucose-monitoring systems can prevent these events in many — but not all — people with this impaired awareness, leaving a substantial number of people at risk.
In type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the islets of the pancreas. Therefore, people with type 1 diabetes need lifelong treatment with insulin, which helps transport the sugar glucose from the bloodstream into cells, where it serves as a key energy source. Even with insulin therapy, people with type 1 diabetes frequently experience fluctuations in blood sugar levels.
According to an article published online in Diabetes Care (18 April 2016), new clinical trial results show that transplantation of pancreatic islets — cell clusters that contain insulin-producing cells — prevents severe, potentially life-threatening drops in blood sugar in people with type 1 diabetes. The study also found that the treatment was effective for people who experienced episodes of severe hypoglycemia — low blood sugar levels that can lead to seizures, loss of consciousness and death — despite receiving expert care.
The Phase 3 trial was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and was conducted by the NIH-sponsored Clinical Islet Transplantation (CIT) Consortium. The investigators designed the study in consultation with the FDA to enable potential future licensure of the manufacture of purified human pancreatic islets.
Clearly, the treatment carried risks, including infections and lowered kidney function as a result of people taking the immune-suppressing drugs needed to prevent rejection of the donor islets. Although some of the side effects were serious, none led to death or disability. According to the NIH, while the procedure is still experimental, and with risks that must be weighed carefully, the promise of islet transplantation is undeniable and encouraging, as even with the best care, about 30% of people with type 1 diabetes aren’t aware of dangerous drops in blood glucose levels.
The current study enrolled 48 people who had persistent impaired awareness of hypoglycemia and experienced severe hypoglycemic events despite expert care by a diabetes specialist or endocrinologist. The study used a standardized manufacturing protocol to prepare purified islets from the pancreases of deceased human donors, and all study participants received at least one transplant of islets injected into the portal vein, the major vessel that carries blood from the intestine into the liver. Islet recipients currently must take immunosuppressive drugs for the rest of their lives to prevent their immune systems from rejecting the transplanted cells.
Results showed that one year after the first transplant, 88% of study participants were free of severe hypoglycemic events, had established near-normal control of glucose levels, and had restored hypoglycemic awareness. After two years, 71% of participants continued to meet these criteria for transplant success. Participants who still needed insulin 75 days after transplant were eligible for another islet infusion. Twenty-five participants received a second transplant, and one received three. After one year, 52% of study participants no longer needed insulin therapy.
The authors are continuing to follow participants to determine whether the benefits of restoring near-normal blood glucose control and protection from severe hypoglycemic events will outweigh the risks associated with chronic immunosuppression.