They were simultaneously published online today in the British medical journal The Lancet. The studies were conducted by the National Institutes of Health’s international network of researchers, Type 1 Diabetes TrialNet Study Group, which is led by the Miller School’s Jay Skyler, M.D.
Both TrialNet studies aimed to preserve secretion of insulin, the hormone that controls blood glucose levels — one with the drug abatacept, and the other with a vaccine called glutamic acid decarboxylase (GAD). When type 1 diabetes is diagnosed, most patients retain a limited ability to make insulin, which is generally lost rapidly over the next one to two years. All study participants received intensive management of their diabetes during the trial, with a goal of keeping HbA1c levels within current ADA recommendations. HbA1c is the measure of the level of glucose in your blood over time.
In the first study, abatacept (Orencia), an immune system modulator currently used to treat several inflammatory diseases, was evaluated in 112 people, ages 6 to 36, with newly diagnosed type 1 diabetes. Participants were randomized to receive injections of either abatacept or placebo over two years. The group treated with abatacept had a 9.6-month delay in the progression of loss of insulin production. After two years, a marker for the production of insulin was 59 percent higher in the participants treated with abatacept compared to the placebo group. Long-term retention of the ability to make even small amounts of insulin is associated with better glucose control and improved outcomes in diabetes.
In the second study, GAD-alum, an antigen-based therapy aiming to suppress the immune response, was tested in 145 people, ages 3 to 45, with newly diagnosed type 1 diabetes. Participants were randomized into three groups to receive two or three doses of GAD-alum or alum alone over four to 12 weeks. During one year of treatment, the vaccine showed no evidence of preserving insulin secretion.
Adverse effects were minimal for both drugs, especially among children, who account for 13,000 new cases of type 1 diabetes each year in the United States.
“We learn something important from every study, and we build on everything we learn,” said Dr. Skyler, TrialNet Study Group chair, and professor of medicine and deputy director of the Diabetes Research Institute at the Miller School. “Both positive and negative studies help us develop more effective strategies to prevent and treat type 1 diabetes. We will continue to follow people in both studies. It is still early, but there is good reason to believe that some of the drugs being developed to alter immune responses, either alone or in combination with other therapies, will lead to treatments that prevent, postpone, or stop progression of type 1 diabetes.”
Type 1 diabetes is an autoimmune disease that accounts for 5 to 10 percent of diagnosed cases of diabetes in the United States—up to 2.5 million people. It develops when a person’s own immune system destroys beta cells in the pancreas. Beta cells sense blood glucose and produce the hormone insulin, which regulates glucose levels and converts it to energy.
Formerly called juvenile onset diabetes, type 1 diabetes usually develops in children and young adults. To maintain good control of their blood glucose levels, people with this form of diabetes typically need three or more insulin injections a day or treatment with an insulin pump, as well as careful monitoring of blood glucose and attention to diet and exercise. Well controlled glucose is critical to preventing or delaying serious damage to the eyes, nerves, kidneys, heart, and blood vessels.
The destruction of insulin producing cells by the immune system begins well before the symptoms of diabetes occur and continues long after it is diagnosed, often until no insulin production remains. During the early months after diabetes is diagnosed, most people still have some functioning beta cells. These cells, with the help of insulin injections, make it easier to control blood glucose. If this period can be extended, researchers hope that more people will be able to achieve better control of their blood glucose. In some cases, intervention may be possible before clinical diabetes develops.