Autoimmune destruction of the insulin producing beta cells of the pancreas is the primary cause of type 1 diabetes. Research has shown that the T-Cells require a co-stimulating signal to attain a fully active state. Interventions to prevent this co-stimulation have potential to prevent further beta cell loss in recently diagnosed type 1 diabetes patients. A study conducted by Dr Jay S Skyler and his colleagues at the Diabetes Research Institute, University of Miami Miller School of Medicine, FL, USA and Type 1 Diabetes TrialNet Abatacept Study Group has shown that abatacept helps modulate this co-stimulation and slows beta cell destruction, albeit for only the first six months of treatment. This study was first published in the The Lancet Online First edition.
The study enrolled recently diagnosed patients with type 1 diabetes aged between 6 and 45 years. The patients were randomized to two arms of the trial. 77 received abatacept (10 mg/kg, maximum 1000 mg per dose) and 35 were administered a placebo. The treatment was given as an infusion on days 1, 14, 28, and then on monthly intervals for two years. A total of 27 such infusions were given to the patients. Postprandial (Post-meal) concentrations of C-peptide levels were measured in blood. C-peptide level in the blood is a direct indicator of insulin secretion from the beta cells and thus an estimation of beta cell function. Adjusted C-peptide levels at 2 years were 59% higher in the group that was getting abatacept than those on the placebo. It is interesting to note that this apparent preservation of beta cells lasted only during the first six months of the treatment. After six months, both groups had a similar rate of decrease in beta cell function as well as beta cell mass.
The researchers said:
“The beneficial effect suggests that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes. Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing us to speculate that T-cell activation lessens with time. Further observation will establish whether the beneficial effect continues after cessation of abatacept infusions.”
The researchers also added that the mechanism of action of abatacept was such that it should be tested in a trial aimed at prevention. Abatacept would also seem to be an appropriate component of a combination therapy protocol for treating recently diagnosed type 1 diabetes patients. Testing abatacept in these situations may require a subcutaneous version that is in developmental stage right now. They concluded that it would not be appropriate to use abatacept in clinical practice for type 1 diabetes until more data was available.
In a comment linked to this report, Dr Bart O Roep, Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Netherlands, stated that this study:
“..underscores that the future treatment of type 1 diabetes will probably involve immunotherapy, supplementary to treatment of insulin deficiency.”
Written by Barry Windsor