According to an article published early online and in an upcoming edition of The Lancet, type I diabetes was not prevented or delayed by administering insulin (via the nasal cavity) to infants and children whose genetic profiles and presence of autoantibodies put them at a high risk of developing the condition.
The authors of the study, Dr Kirsti Näntö-Salonen and Dr Olli Simell (University of Turku, Finland) and colleagues, performed the clinical trial after promising results from animal studies. Previous research in mouse models revealed that several different avenues of insulin therapy could reduce the incidence of autoimmune (type I) diabetes. Results were most pronounced when young animals in the early stages of the disease were treated.
The analysis by Näntö-Salonen, Simell, and colleagues began with cord blood samples of 116,720 infants (index) from three hospitals in Finland and 3,430 of their siblings. The researchers tested for genetic profiles that indicated susceptibility to type I diabetes, and an increased risk profile was seen in 17,397 of the index infants and 1,613 of the siblings. Of these, 11,225 and 1,574, respectively, agreed to receive screenings for diabetes-associated autoantibodies (first recognizable sign of the ongoing autoimmune process) at every 3 – 12 months. The randomized controlled portion of the study consisted of 264 children (224 index and 40 siblings) who tested positive for two or more autoantibodies in consecutive samples taken 3 – 6 months apart. An insulin group consisted of randomly selected 115 index children and 22 siblings, and a placebo group consisted of the remaining 109 index children and 18 siblings. The average (median) duration of intervention was 1.8 years.
Results indicated that the 49 index children in the insulin group and 47 in the placebo group were diagnosed with type I diabetes – not a significant difference. In addition, 42 in the insulin group and 38 in the placebo group continued treatment until diagnosis. Their yearly rates of diabetes onset were 16.8% and 15.3%, respectively. In the insulin group, 7 siblings were diagnosed with diabetes compared to 6 siblings in the placebo group. The total number of diabetes cases diagnosed in all randomized children was 56 in the insulin group and 53 in the placebo group. “Administration of nasal insulin did not delay or prevent type I diabetes in children with genetically conferred risk of disease, even when started soon after antibodies to the condition were detected,” conclude the authors.
An accompanying comment written by Dr David B Dunger and Dr John Todd (University of Cambridge, UK) adds: “As Näntö-Salonen and colleagues and others have shown, autoantibody seroconversion in the first 1-3 years of life may be a common prerequisite for development of type I diabetes, which would suggest that an early window of susceptibility exists, after which seroconversion and type I diabetes are much less likely.”
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
Kirsti Näntö-Salonen, 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
The Lancet (2008).
DOI:10.1016/S0140-6736(08)61309-4
Written by: Peter M Crosta