Trial of Intranasal Insulin in Children and Young Adults at Risk of Type 1 Diabetes (INIT II)

• B cell function: measured as 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.

• 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.

In people with type I diabetes the beta cells of the pancreas no longer make insulin because the body's immune system has attacked and destroyed the beta cells. It is thought that exposure of the mucous membranes to insulin may cause act like a vaccine effect whereby protective immune cells are stimulated and these then counteract the "bad" immune cells that damage the beta cells. This study aims to determine if intranasal insulin can protect beta cells and stop progression to diabetes in individuals who are at risk.

• Biological: Intranasal insulin
• Other: Placebo

• Active Comparator: 1
  Intervention: Biological: Intranasal insulin
• Placebo Comparator: 2
  Intervention: Other: Placebo

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. Normal oral glucose tolerance test (OGTT).
5. FPIR at or above threshold - Primary Stratum - 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). Secondary Stratum: Greater than or equal 1st percentile, less than 10th percentile for siblings, offspring and second-degree relatives of someone with T1D (greater than or equal to 50uU/ml less than 100 uU/ml if aged greater than or equal to 8 years or greater than or equal to 20 uU/ml less than 60uU/ml if aged less than 8 years)
6. 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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