Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/7184
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Type: Journal article
Title: Pancreatic β-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes
Other Titles: Pancreatic beta-cell function and immune responses to insulin after administration of intranasal insulin to humans at risk for type 1 diabetes
Author: Harrison, L.
Honeyman, B.
Steele, C.
Stone, N.
Sarugeri, E.
Bonifacio, E.
Couper, J.
Coleman, P.
Citation: Diabetes Care, 2004; 27(10):2348-2355
Publisher: Amer Diabetes Assoc
Issue Date: 2004
ISSN: 0149-5992
1935-5548
Statement of
Responsibility: 
Leonard C. Harrison, Margo C. Honeyman, Cheryl E. Steele, Natalie L. Stone, Elena Sarugeri, Ezio Bonifacio, Jennifer J. Couper, and Peter G. Colman
Abstract: OBJECTIVE:Mucosal administration of insulin retards development of autoimmune diabetes in the nonobese diabetic mouse model. We conducted a double-blind crossover study in humans at risk for type 1 diabetes to determine if intranasal insulin was safe, in particular did not accelerate beta-cell destruction, and could induce immune effects consistent with mucosal tolerance. RESEARCH DESIGN AND METHODS:A total of 38 individuals, median age 10.8 years, with antibodies to one or more pancreatic islet antigens (insulin, GAD65, or tyrosine phosphatase-like insulinoma antigen 2) were randomized to treatment with intranasal insulin (1.6 mg) or a carrier solution, daily for 10 days and then 2 days a week for 6 months, before crossover. The primary outcome was beta-cell function measured as first-phase insulin response (FPIR) to intravenous glucose at 0, 6, and 12 months and then yearly; the secondary outcome was immunity to islet antigens, measured monthly for 12 months. RESULTS:No local or systemic adverse effects were observed. Diabetes developed in 12 participants with negligible beta-cell function at entry after a median of 1.1 year. Of the remaining 26, the majority had antibodies to two or three islet antigens and FPIR greater than the first percentile at entry, as well as beta-cell function that generally remained stable over a median follow-up of 3.0 years. Intranasal insulin was associated with an increase in antibody and a decrease in T-cell responses to insulin. CONCLUSIONS:Results from this pilot study suggest that intranasal insulin does not accelerate loss of beta-cell function in individuals at risk for type 1 diabetes and induces immune changes consistent with mucosal tolerance to insulin. These findings justify a formal trial to determine if intranasal insulin is immunotherapeutic and retards progression to clinical diabetes.
Keywords: Islets of Langerhans; Nasal Mucosa; Humans; Diabetes Mellitus, Type 1; Prediabetic State; Autoimmune Diseases; Insulin; Blood Glucose; Insulin Antibodies; Glucose Tolerance Test; Treatment Outcome; Administration, Intranasal; Drug Administration Schedule; Severity of Illness Index; Risk Assessment; Follow-Up Studies; Cross-Over Studies; Double-Blind Method; Dose-Response Relationship, Drug; Reference Values; Adolescent; Adult; Child; Female; Male
Rights: Copyright © 2004 by the American Diabetes Association.
RMID: 0020041818
DOI: 10.2337/diacare.27.10.2348
Appears in Collections:Paediatrics publications

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