Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus (TN20)

A minimum of 40 eligible participants will be identified for study participation from the TrialNet Pathway to Prevention study. Participants must have a relative with type 1 diabetes and be positive for insulin autoantibodies and at least one other autoantibody. All participants will receive active treatment of recombinant insulin treatment in capsules of either 67.5 mg daily or 500mg every other week. Participants will need to visit the study site up to eleven times over one year for blood tests and other study procedures. During the beginning treatment phase there are two visits one month apart for those given the 67.5 mg dose, and three visits two weeks apart to titrate the dose for those in the 500mg treatment group. There are three additional treatment visits at months 2, 3, and 6 and 4 additional visits for follow-up at months 7, 8, 9 and 12. The primary outcome is the change in immune function as assessed by change in level or quality of T lymphocyte or autoantibody biomarkers measured between 13 and 26 weeks compared to baseline. .

Inclusion criteria

• Participants in TrialNet Natural History/Pathway to Prevention Study (TN01); is relative of proband with type 1 diabetes
• Between ages 3-45 with normal Oral Glucose Tolerance Test (OGTT) or between ages 3-7 with an abnormal OGTT
• Confirmed positive for insulin autoantibodies within previous six months
• Confirmed positive for one or more other autoantibodies on two separate occasions within the past six months

Exclusion criteria

• Diagnosed with type 1 diabetes
• History of treatment with insulin or oral hypoglycemic agent
• History of therapy with immunosuppressive drugs or non-physiologic glucocorticoids within the past two years for a period of more than three months
• Ongoing use of medications known to influence glucose tolerance
• Pregnant or intending to become pregnant while on study or lactating