Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults.
BACKGROUND
Intranasally applied insulin is one of the antigen-specific therapies currently tested in clinical type 1 diabetes prevention trials, for example, in the Type 1 Diabetes Prediction and Prevention Study (DIPP). The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study.


METHODS
We used a randomised, placebo-controlled, double-blinded crossover study design with 3-week treatment periods to study the effects of once-daily intranasal application of human short-acting insulin without absorption-enhancing adjuvants in 20 non-diabetic adults. The selected 60 IU dose of insulin was equivalent to the weight-based dose used for the DIPP children. We investigated self-monitored blood glucose concentrations, nasal insulin effects and induction of diabetes-associated autoantibodies.


RESULTS
The two treatment periods showed no differences in blood glucose concentrations or in the frequency of blood glucose values higher than 3.0 mmol/L. Of the eight measured hypoglycaemic values, only one, which occurred during placebo therapy, was associated with symptoms. Rhinoscopy revealed no nasal irritation, and mucociliary clearance, nasal airway patency and nasal airflow resistance were not affected by the insulin therapy. Eleven subjects complained of transient nasal stinging or unpleasant odour and one subject reduced the dose because of nasal irritation. The treatment did not induce production of any of the four diabetes-associated autoantibodies.


CONCLUSIONS
Short-term use of intranasal insulin without absorption enhancers was predominantly well tolerated, the risk of hypoglycaemia was minimal and no objective nasal adverse effects were detected.
Kupila
A
A
Department of Paediatrics, University of Turku, Turku, Finland. Antti.Kupila@Tyks.Fi
Sipilä
J
J
Keskinen
P
P
Simell
T
T
Knip
M
M
Pulkki
K
K
Simell
O
O
D000281:Administration, Intranasal; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D010919:Placebos
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos