Memorandum
This week’s issue of JAMA featured the results of the Pre-POINT trial, which examined the safety and immune effects of oral insulin in a population of 25 autoantibody-negative children at genetic risk for type 1 diabetes. The preliminary study found that oral insulin was safe and – at the 67.5 mg daily dose (much higher than has been tested previously) – appeared to modulate the immune response in a beneficial manner. In an accompanying editorial, Dr. Jay Skyler (University of Miami Miller School of Medicine, Miami, FL) notes that while earlier oral insulin studies measured metabolic outcomes such as C-peptide, Pre-POINT used newer tools to directly measure the immune response to the therapy. The study was not designed to investigate hard outcomes such as progression to diabetes. The safety data and signs of immune benefit lay the groundwork for a larger, more definitive phase 3 trial. In the editorial, Dr. Skyler notes that a pivotal trial would need to enroll younger patients (down to below one year old, as opposed to the minimum age of two years used in Pre-POINT) with potentially more inclusive enrollment criteria. Dr. Skyler mentions some other promising areas of type 1 diabetes prevention research, specifically injectable proinsulin vaccine (phase 2 trials expected to begin in 2016), proinsulin-secreting bacteria paired with other immuno-modulatory compounds, and the hypertension drug methyldopa (in pilot studies) that may block the immune response to insulin.
Another item of note for type 1 diabetes in the same JAMA issue: a database study from the Barbara Davis Center found a 55% increase in the incidence of DKA at diagnosis from 30% to 46% between 1998 and 2012, a higher rate than has been reported elsewhere in the developed world – if any readers have theories on why this would be, please let us know.