A phase 3 trial for the transplantation of human islets shows potential as a treatment for impaired awareness of hypoglycemia in type 1 diabetics
Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes, affects 0.25% of the American population under 20 years of age. In type 1 diabetes, the beta cells of the pancreas produce little or no insulin, a hormone required for the movement of sugar from the blood to the cells in order to produce energy. Without insulin, type 1 diabetics have extremely high sugar levels in their blood. This can lead to many health complications if not managed properly, including blindness, kidney failure and infections that can lead to amputation. As well, diabetics have an increased risk of developing cardiovascular diseases and suffering nerve damage.
Today, there is no cure for type 1 diabetes. There are, however, many ways to manage type 1 diabetes and ensure that blood glucose levels stay within the normal range. Individuals with type 1 diabetes are recommended to exercise, eat healthy foods, take their prescribed insulin, and monitor their blood sugar. Diabetics are also at risk of hypoglycemia, where the levels of glucose in the blood are too low. This can result from taking too much insulin, not eating enough food, exercising vigorously without eating or adjusting insulin dose, waiting too long in between meals, and drinking excessive or even moderate amounts of alcohol.
Impaired awareness of hypoglycemia (IAH) is a complication of insulin therapy, which affects 30-40% of type 1 diabetics. Individuals with IAH are unable to properly recognize the onset of hypoglycemia. With increasing duration of insulin therapy, type 1 diabetics experience a change in their awareness of hypoglycemia, usually due to a reduction in symptom intensity and/or a change in the symptom profile. Type 1 diabetics with IAH have a three- to six-fold increased risk of a severe hypoglycemic event (SHE), in comparison to type 1 diabetics without IAH. One in three Americans with type 1 diabetes will experience at least one severe hypoglycemic event each year. SHEs are also known as “insulin shocks” and are defined as any hypoglycemic event severe enough to require assistance. SHEs interfere with proper maintenance of blood glucose levels and contribute to an increased risk of medical complications (like a diabetic coma) and mortality. Current therapies aimed at preventing SHEs are effective in 50-80% of type 1 diabetes patients, leaving a large number of diabetics at risk.
In a new Phase 3 clinical trial published in the journal Diabetes Care, researchers have evaluated the efficacy and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. Pancreatic islets are regions of the pancreas that contain hormone-producing cells, including beta cells. In this phase 3 study, 48 type 1 diabetics who were unresponsive to SHE/IAH treatment were enrolled. Pancreases from decreased donors were processed, and islets were purified. Participants received immunosuppression (for proper acceptance of the incoming cells) and researchers then transplanted the purified islets into the participants. They measured their blood glucose levels and number of SHEs a year after the first transplant. Researchers chose the primary end points (goals) of the study: for participants to have an HbA1c of <7.0% and to be free from SHEs a year after the transplant. HbA1c is a test that gives an idea of the average blood sugar level for the previous 2 months, and is expected to be less than 7% in diabetics who are properly managing their sugar levels.
Of the 48 study participants, 87.5% successfully met the primary end points at 1 year post-transplant, and 71% met the ends points at 2 years. The average HbA1c level was 5.6%, at both 1 and 2 years post-transplant. Researchers also recorded that two of the participants experienced infections as a result of immunosuppression and post-procedural bleeding occurred in 8.9% of participants, but there were no study-related deaths or disabilities. As well, all participants were able to restore their awareness of hypoglycemia awareness.
Taken together, these results show that transplantation of human islets could serve as a viable therapeutic option for type 1 diabetes patients who are unresponsive to the typical treatments for IAH and SHEs. All participants were able to restore their awareness of hypoglycemia, and severe hypoglycemic events were no longer present in more than half of the participants. As with any treatment, the possible side effects should be considered and compared to the potential benefits.
Written By: Alexandra Lostun, BSc