Study: Immunotherapy Halts Insulin Destruction in Type 1 Diabetes

A new study suggests that a form of immunotherapy given to newly diagnosed patients with type 1 diabetes (T1D) could halt the destruction of beta cells before all insulin production is lost.

Authors of the study, appearing in Science Translational Medicine, note that it is small and that much more work is needed, but the results nonetheless capitalize on years of research to understand how immune system pathways cause beta cell loss. In turn, the attack on beta cells eliminates insulin production, and forces patients with T1D to spend a lifetime taking insulin injections at great cost and inconvenience.

Understanding the steps of the immune system’s attack led to this new discovery, as scientists have known for some that the initial destruction of beta cells leaves some insulin, as well as a related C-peptide. In a healthy patient, the 2 are typically produced together by the pancreas, when it releases insulin to regulate blood glucose. C-peptide, in fact, is a marker for insulin and tests for it are used to determine if the body is producing insulin.

In the months after T1D is diagnosed, residual levels of insulin and C-peptide disappear, and the patient with T1D needs increasing amounts of insulin each day to manage blood glucose levels.

Scientists at King’s College and Cardiff University, led by Mohammad Alhadj Ali, MD, PhD, MSc, followed up on successful work with peptides for patients with allergies. In a placebo-controlled trial of 27 patients, they found that patients who were within the first 100 days of T1D diagnosis could be treated every 2 to 4 weeks with proinsulin peptide immunotherapy, an approach that prior work suggested would avoid problems of triggering whole-antigen reactions.

After 6 months, the patients who received the immunotherapy treatments retained levels of C-peptide, while those in the placebo group continued to see their C-peptide levels decline. “Early C-peptide loss after diagnosis was apparent and significant in the placebo group but much less so in either of the treated groups, and C-peptide loss was significantly lower in the high-frequency group at 3 months,” they wrote.

The authors were cautious about their findings, saying that, “C-peptide measurements can be variable, there were small numbers of subjects in each group with some imbalance between groups in baseline metabolic data.” But the work is a key step, and the authors mentioned a goal of diabetes advocates:

“Future studies will need to be powered for these and for efficacy, should examine whether children are similarly responsive, and begin to explore opportunities for prevention,” they wrote.

Reference

Ajhadj Ali M, Liu YF, Arif S, et al. Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes. Sci Trans Med. 2017;9(402):eaaf7779, doi:10.1126/scitranslmed.aaf7779.