Preserving insulin production in people with newly diagnosed type 1 diabetes
Researchers have discovered that treatment with a medicine that suppresses the immune system, called anti-thymocyte globulin (ATG), preserved insulin production and improved blood glucose (sugar) control for at least a year in people with newly diagnosed type 1 diabetes, as compared to placebo (no medicine). Type 1 diabetes is an autoimmune disease in which a person’s immune system destroys β cells in the pancreas that make insulin. Previous research has shown that people whose bodies continue to produce some insulin had better blood glucose control, less hypoglycemia, and reduced rates of disease complications. Therefore, current research is examining ways to preserve more insulin production in people with type 1 diabetes. For example, a pilot study previously showed that treatment with ATG in combination with a modified protein called GCSF preserved insulin production for 1 year in people with established type 1 diabetes (duration of disease of 4 months to 2 years). ATG is a medicine used to prevent or treat immune system rejection of a transplanted organ; GCSF is used to increase white blood cell counts in people undergoing chemotherapy. Researchers in NIDDK’s Type 1 Diabetes TrialNet built on the results of the pilot study to determine whether treatment with ATG alone or in combination with GCSF could preserve insulin production when used close to the initial diagnosis of type 1 diabetes.
To examine this question, researchers enrolled 89 female and male children and adults, ages 12-42 years, with newly diagnosed type 1 diabetes (less than 100 days since diagnosis) in a three-arm clinical trial. One group received a single course of ATG administered via intravenous infusions; another group received the single course of ATG followed by treatment with GCSF administered through an injection every 2 weeks for a total of 6 doses; and the control group received placebo. The study was blinded, meaning that all participants received the infusions and injections, but did not know whether they were getting medicine or placebo. After 1-year of follow-up, the researchers found that the group receiving ATG alone produced more C-peptide, a measure of insulin production, compared to the placebo group. However, C-peptide levels in the ATG/GCSF group were similar to the placebo group. People in both the ATG and ATG/GCSF groups had better average blood glucose control, as measured by hemoglobin A1c levels, than those in the placebo group. Trial participants continue to be followed to determine if the treatment effects persist for 2 years.
The findings show that a single course of ATG could preserve insulin production in people with newly diagnosed type 1 diabetes for at least 1 year, as compared to placebo, but that GCSF did not enhance benefit. These results differ from the pilot study that found benefit from ATG/GCSF combination therapy, although the pilot study did not examine ATG alone and those participants had more established type 1 diabetes. Like most drugs that target the immune system, ATG treatment has side effects of administration, and its therapeutic effects wane over time after treatment. TrialNet is continuing to follow the study participants, and the data from the 2-year follow-up will help researchers determine whether treatment with ATG alone or in combination with other agents should be pursued for preventing or delaying type 1 diabetes in individuals prior to clinical diagnosis.
Haller MJ, Schatz DA, Skyler JS,…Greenbaum CJ; Type 1 Diabetes TrialNet ATG-GCSF Study Group. Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA1c in new-onset type 1 diabetes. Diabetes Care 41: 1917-1925, doi: 10.2337/dc18-0494, 2018.