• Diagnosis of Diabetes AT 5 years according to ADA/WHO criteria.
  

• B cell function: measured as FPIR yearly and
  
• glucose and insulin responses in OGTT 6monthly.
  
• Insulin Action: Insulin resistance measured by HOMA-R 6 monthly.
  
• Immune function: measured by levels of circulating antibodies to insulin, GAD and IA-2 and T cell responses to proinsulin, denatured insulin, GAD and tetanus at 5 years.
  

Inclusion Criteria:

1. First-degree or second-degree relative of a person with T1D diagnosed before age 40.
2. Age 4-30 years if first-degree relative; age 4-20 years if second-degree relative.
3. Confirmed serum antibodies to two or more islet antigens.
4. HLA not DR2, DQ6.
5. Normal oral glucose tolerance test (OGTT).
6. FPIR at or above threshold: greater than or equal to 10th percentile for siblings, offspring and second-degree relatives of person with T1D (greater than or equal to 100uU/ml if aged 8 or more years OR greater than or equal to 60 uU/ml if aged less than 8) and greater than or equal to the 1st percentile for parents of someone with T1D (greater than ore equal to 60uU/ml).
7. Provision of written consent. -

Exclusion Criteria:

1. History of treatment with insulin or oral hypoglycemic agents
2. Known diabetes by ADA/WHO criteria
3. Pregnant or lactating or of child-bearing potential not using an adequate method of contraception
4. Concomitant disease or treatment which may interfere with assessment or cause immunosuppression, as judged by the investigators.
5. Uncorrected vitamin D deficiency
6. Known alcohol or drug abuse, psychiatric or other condition that could be associated with poor compliance.
7. Known liver disease, or persisting elevation of plasma AST or ALT levels.
8. Impaired renal function

9. Any defect or pathology of nasal passage which would preclude application of the intranasal spray.

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