Insulin inhalers don't prevent Type 1 diabetes in children with antibodies

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial
Original source: The Lancet, Volume 372, Issue 9651
Authors: Kirsti Näntö-Salonen (corresponding author), Antti Kupila, Satu Simell, Heli Siljander, Tiina Salonsaari, Anne Hekkala, Sari Korhonen, Risto Erkkola, Jukka I Sipilä, Lotta Haavisto, Marja Siltala, Juhani Tuominen, Jari Hakalax, Heikki Hyöty, Jorma Ilonen, Riitta Veijola, Tuula Simell, Mikael Knip, Olli Simell
Publication date: 15 November 2008
DOI (digital document ID): 10.1016/S0140-6736(08)61309-4
Requires subscription? Yes
Publicly-available abstract: Yes

Synopsis:
In mice engineered to have risk of Type 1 diabetes, inhaled insulin has been shown to reduce their likelihood of developing diabetes. The authors wanted to know if this would work in humans. They screened a number of infants for a specific gene (the HLA-DQB1 susceptibility allele) linked to increased risk of developing Type 1 diabetes. The siblings of susceptible infants were also screened. Of these, over 11,000 infants and 1500 related siblings consented to having their children's blood screened for diabetes at 3-12 month intervals. [One would presume that for minors, their parents would have been the ones giving consent.] From these, 224 infants and 40 of their siblings (all of whom tested positive for two or more diabetes-specific antibodies) were entered into a trial in which some would be given short-acting human insulin (1 unit/kg) or placebo once a day intranasally (inhaled) until they developed Type 1 diabetes and needed traditional injectable insulin. The children were studied for an average length of 1.8 years (range lasted from 0-9.7 years). The study ended early because the insulin did not show any benefit -- as many children on insulin as on placebo developed diabetes, over similar ranges of time from the start of the trial.

Reliability:
Almost all of the authors are either medical doctors or professors of medicine. The number of children studied was not very large (only about 260), and they had already developed diabetes-related antibodies.

Would the results have been different if insulin had been administered before antibodies had developed, with the trial endpoint being the development of antibodies? Would the results have been different if a basal insulin had been used, or a different dosage?

As far as I know there is no inhaled insulin treatment for Type 1 diabetes in people. Does inhaled insulin work as primary treatment in those of that strain of mice who have developed diabetes? If it does, then the experiment is "comparing apples and oranges", and the analogous human experiment would require injected insulin.

Practical Applications:
Had there been a reduction in the number of children studied who developed Type 1 diabetes, or a significant delay in their development of Type 1 diabetes, then inhaled insulin therapy could have been used as a preventative (prophylactic) measure. The negative findings show that it cannot be.

Ethics Note:
The study was registered with ClinicalTrials.gov, number NCT00223613. Since the subjects were likely minors, their parents would have been required to provide the necessary consent.

This synopsis was based on the abstract only.