Insulin immunotherapy for pretype 1 diabetes

Purpose of review Loss of tolerance to insulin likely contributes to the immunopathogenesis of type 1 diabetes (T1D). Several large clinical trials and smaller mechanistic studies have failed to demonstrate the efficacy of insulin antigen therapy. The growing awareness of the heterogeneity of T1D likely affects the response to various immune therapies including insulin. Identification of biomarkers of clinical response will provide further insight into mechanisms leading to the disease and classify responders in the quest for personalized therapy. Recent findings Several biomarkers have identified subpopulations in posthoc analyses that showed benefit from oral insulin even though the placebo-controlled study was as a whole unsuccessful. High insulin autoantibody titer, low first phase insulin response, and high Diabetes Prevention Trial-Type 1 Risk Score identify at-risk relatives more likely to benefit from oral insulin. Future incorporation of human leukocyte antigen and the variable number of tandem repeats polymorphism located in the insulin gene promoter (INS VNTR) is of interest for both primary and secondary prevention studies. Summary Although primary and secondary prevention trials using oral insulin are ongoing, those completed have been largely unsuccessful. However, we believe that oral insulin should be considered in future trials as part of combination therapies as prerandomization biomarker testing is refined.
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: DIABETES AND ENDOCRINE PANCREAS II: Edited by Peter Gottlieb Source Type: research