Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

Inclusion Criteria:

1. Have a proband with T1DM. A proband is an individual diagnosed with diabetes before age 40 and started on insulin therapy within 1-year of diagnosis. Probands considered to have type 1 diabetes by their physician who do not meet this definition will be referred to the TrialNet Eligibility Committee.
2. If the proband is a parent, sibling or a child, the study participant must be 3 -45 years of age. If the proband is a second or third degree relative (i.e. niece, nephew, aunt, uncle, grandparent, cousin, or half-sibling), the study participant must be 3-20 years of age.
3. Willing to sign Informed Consent Form.

4. OGTT performed within 7 weeks prior to randomization in which:

   • fasting plasma glucose < 110 mg/dL (6.1 mmol/l), and
   • 2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)
5. mIAA confirmed positive within the previous six months.
6. Two samples with at least one autoantibody other than mIAA positive within the previous six months.

Exclusion Criteria:

1. Does not satisfy the above inclusion criteria. Subjects with mIAA positive but no other autoantibodies positive are not eligible for randomization.
2. Has severe active disease, e.g. chronic active hepatitis, severe cardiac, pulmonary, renal, hepatic, immune deficiency and/or disease that is likely to limit life expectancy or lead to therapies such as immunosuppression during the time of the study.
3. Prior participation in a trial for prevention of T1DM, e.g. nicotinamide, insulin, immunosuppressive drugs.
4. History of treatment with insulin or oral hypoglycemic agent.
5. History of therapy with immunosuppressive drugs or glucocorticoids within the past two years for a period of more than three months.
6. Ongoing use of medications known to influence glucose, i.e. sulfonylureas, growth hormone, metformin, anticonvulsants, thiazide or potassium depleting diuretics, beta adrenergic blockers, niacin. Subjects on such medications should be changed to a suitable alternative, if available, and will become eligible one month after medication is discontinued.
7. Pregnant or intends to become pregnant while on study or lactating.
8. Deemed unlikely or unable to comply with the protocol.

9. OGTT that reveals Diabetes, Impaired Glucose Tolerance (IGT), or Impaired Fasting Glucose (IFG).

   Diabetes is defined by:

   • fasting plasma glucose ³ 126 mg/dL (7 mmol/l), OR
   • 2 hour plasma glucose ³ 200 mg/dL (11.1 mmol/l)

   IGT is defined by:

   • fasting plasma glucose < 126 mg/dL (7 mmol/l), and
   • 2 hour plasma glucose 140-199 mg/dL (7.8 - 11mmol/l),

   IFG is defined by:

   • fasting plasma glucose 110-125 mg/dL (6.1-6.9 mmol/l) AND
   • 2 hour plasma glucose < 140 mg/dL (7.8 mmol/l)
10. Subject has HLA DQA1*0102, DQB1*0602 haplotype.