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
Abstract
Background In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease. Methods At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes. 17 397 infants and 1613 siblings had increased genetic risk, of whom 11 225 and 1574, respectively, consented to screening of diabetes-associated autoantibodies at every 3-12 months. In a double-blind trial, we randomly assigned 224 infants and 40 siblings positive for two or more autoantibodies, in consecutive samples, to receive short-acting human insulin (1 unit/kg; n=115 and n=22) or placebo (n=109 and n=18) once a day intranasally. We used a restricted randomisation, stratified by site, with permuted blocks of size two. Primary endpoint was diagnosis of diabetes. Analysis was by intention to treat. The study was terminated early because insulin had no beneficial effect. This study is registered with ClinicalTrials.gov, number NCT00223613. Findings Median duration of the intervention was 1.8 years (range 0-9.7). Diabetes was diagnosed in 49 index children randomised to receive insulin, and in 47 randomised to placebo (hazard ratio [HR] 1.14; 95% C…
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A trial investigating intranasal insulin observed negative results.
“Negative results were also observed in another trial investigating intranasal insulin.145”
From Type 1 diabetes (2018) · cites this paper as [145]
Nicotinamide and intranasal insulin have not been shown to delay or prevent diabetes onset.
“Other agents used for secondary prevention, nicotinamide and intranasal insulin, have not been shown to delay or prevent diabetes onset.132,133”
From Type 1 diabetes (2014) · cites this paper as [133]
Subcutaneously or intranasally delivered insulin was found to have no preventive effects.
“Subcutaneously or intranasally delivered insulin was found to have no preventive effects.39,48”
From The future of type 1 diabetes therapy (2025) · cites this paper as [39]
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Self-citationMaternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring
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Self-citation
- Authors
- Näntö-Salonen, K., Kupila, A., Simell, S., Siljander, H., Salonsaari, T., Hekkala, A., Korhonen, S., Erkkola, R., Sipilä, J. I., Haavisto, L., Siltala, M., Tuominen, J., Hakalax, J., Hyöty, H., Ilonen, J., Veijola, R., Simell, T., Knip, M., & Simell, O.
- Affiliations
- University of Turku (FI)
- University of Helsinki (FI)
- Tampere University Hospital (FI)
- University of Oulu (FI)
- Tampere University (FI)
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 372
- Issue
- 9651
- Pages
- 1746-1755
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2157440365
- Cited by
- 382
- References
- 32
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 19 · 2023: 15 · 2022: 16 · 2021: 21 · 2020: 19 · 2019: 16 · 2018: 19 · 2017: 8 · 2016: 21 · 2015: 33 · 2014: 19 · 2013: 36 · 2012: 30
- FWCI
- 18.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes prevention, nasal insulin, diabetes-associated autoantibodies, high genetic risk, children, siblings, diabetes onset, diabetes screening, cord blood screening, early trial termination, diabetic mouse model, insulin resistance index
- MeSH terms
- Administration, Intranasal, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Finland, Genetic Testing, Genotype, HLA-DQ Antigens, Humans, Hypoglycemic Agents, Infant, Infant, Newborn, Insulin, Male, Risk Factors, HLA-DQ beta-Chains
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