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Type 1 diabetes (T1D) accounts for 5-10% of all diabetes; and for reasons that are not understood, the incidence of this disease is rising in Western countries and will double by 2040. The hallmark of T1D is immune-mediated destruction of pancreatic β cells and a requirement for exogenous insulin to support glucose metabolism. The fact that T1D has an autoimmune pathology has been known for many years; and the possibility that immunomodulation might change its natural history was demonstrated more than 30 years ago when Stiller and colleagues showed that administration of cyclosporin slowed the loss of β cells and the requirement for insulin in patients with newly diagnosed T1D. However, drug toxicity, particularly nephrotoxicity limited enthusiasm for this form of therapy. An additional drawback of this approach was that the therapeutic effect of cyclosporine vanished with cessation of treatment. Other immunosuppressive agents (e.g., abatacept, anakinra, etanercept) have demonstrated therapeutic efficacy in recent-onset T1D, but even with continued use, they failed to show durable effects.

 

A recent study has demonstrated the potential of a novel approach to change the natural history of T1D. Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in multiple preclinical models of autoimmune diseases. This intervention is called peptide immunotherapy and has gained favor in clinical allergy, where it avoids the problem of using whole antigens that might trigger severe hypersensitivity. However, it has never been used in an effort to prevent the immune destruction of β cells in T1D. A report published in Science Translational Medicine in August 2017 has provided strong evidence that this approach might stop the progression of T1D. In this study, proinsulin peptide or a placebo preparation was injected intradermally every 2 or 4 weeks for 6 months in 27 patients with newly diagnosed T1D. After a total of 1 year of follow-up, patients who received peptide injections had no decline in C-peptide (a measure of insulin reserve) while those who received placebo had a progressive decline. In addition, the requirement for daily insulin increased by 50% over 12 months in the patients who received placebo but was unchanged in the who received peptide immunotherapy. It is hoped that these exciting findings will lead to a larger trial assessing the efficacy of this novel approach for slowing or stopping the progression of T1D.

 

References

Alhadj Ali M, Liu YF, et al. Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes. Sci Transl Med. 2017;9:402.

 

Rewers M, Gottlieb P. Immunotherapy for the prevention and treatment of type 1 diabetes: human trials and a look into the future. Diabetes Care. 2009;32:1769-1782.

 

Stiller CR, Dupré J, Gent M, et al. Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science. 1984;223:1362-1367.

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