In a first, scientists have developed a treatment that can delay type 1 diabetes by two or more years among people who are at high risk.
The research, published in the New England Journal of Medicine, involved treatment with an anti-CD3 monoclonal antibody (teplizumab). Researchers from Yale University in the US enrolled 76 participants ages 8-49 who were relatives of people with type 1 diabetes, had at least two types of diabetes-related autoantibodies (proteins made by the immune system), and abnormal glucose (sugar) tolerance. Participants were randomly assigned to either the treatment group, which received a 14-day course of teplizumab, or the control group, which received a placebo.
All participants received glucose tolerance tests regularly until the study was completed, or until they developed clinical type 1 diabetes -- whichever came first. During the trial, 72 per cent of people in the control group developed clinical diabetes, compared to only 43 per cent of the teplizumab group.
The median time for people in the control group to develop clinical diabetes was just over 24 months, while those who developed clinical diabetes in the treatment group had a median time of 48 months before progressing to diagnosis. Type 1 diabetes develops when the immune system's T cells mistakenly destroy the body's own insulin-producing beta cells. Insulin is needed to convert glucose into energy.
Teplizumab targets T cells to lessen the destruction of beta cells. "Previous clinical research found that teplizumab effectively slows the loss of beta cells in people with recent onset clinical type 1 diabetes, but the drug had never been tested in people who did not have clinical disease," said Kevan C Herold, of Yale University. "We wanted to see whether early intervention would have a benefit for people who are at high risk but do not yet have symptoms of type 1 diabetes," Herold.
The effects of the drug were greatest in the first year after it was given, when 41 per cent of participants developed clinical diabetes, mainly in the placebo group. Many factors, including age, could have contributed to the ability of teplizumab to delay clinical disease, since at-risk children and adolescents are known to progress to type 1 diabetes faster than adults.
Faster progression of type 1 diabetes is associated with a highly active immune system, which may explain the impact of immune system-modulating drugs like teplizumab. Other data collected from the trial may help researchers to understand why certain people responded to treatment.
Participants who responded to teplizumab tended to have certain autoantibodies and other immune system characteristics. The research team also cautioned that the study had limitations, including the small number of participants, their lack of ethnic diversity, and that all participants were relatives of people with type 1 diabetes, potentially limiting the ability to translate the study broadly.