CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1

Inclusion Criteria:

   - Participant in TrialNet Natural History/Pathway to Prevention Study and thus, a
   relative of a proband with T1DM.

   - Between the ages of 1-45 years at the time of enrollment in TN01 and age ≥ 6 at time
   of randomization in this trial.

   - Willing to provide Informed Consent or have a parent or legal guardian provide
   informed consent if the subject is <18 years of age.

   - Normal glucose tolerance by OGTT confirmed within 7 weeks (no more than 52 days) of
   baseline (visit 0). If previous abnormal glucose tolerance, has had two consecutive
   OGTTs with normal glucose tolerance.

      1. Fasting plasma glucose < 110 mg/dL (6.1 mmol/L), and

      2. 2 hour plasma glucose <140 mg/dL (7.8 mmol/L), and

      3. 30, 60, or 90 minute value on OGTT< 200mg/dL (11.1 mmol/L)

   - At least two diabetes-related autoantibodies confirmed to be present on two occasions,
   not including mIAA. Confirmation of 2 positive autoantibodies must occur within the
   six months prior to randomization, but the confirmation does not have to involve the
   same 2 autoantibodies.

   - Weight ≥ 20 kg at Baseline Visit.

   - If a female participant with reproductive potential, willing to avoid pregnancy and
   undergo pregnancy testing prior to each infusion.

   - At least three months from date of last live immunization.

   - Willing to forgo live vaccines while receiving treatment on study and for three months
   following last study drug administration.

Exclusion Criteria:

   - Abnormal Glucose Tolerance or Diabetes

      1. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L), or

      2. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or

      3. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)

   - Insulin autoantibodies (mIAA).

   - Are immunodeficient or have clinically significant chronic lymphopenia.

   - Have an active infection at time of randomization.

   - Have a positive PPD test result or history of previously treated TB, or positive
   interferon-gamma release assay (IGRA) test.

   - Be currently pregnant or lactating, or anticipate getting pregnant within 3 months of
   the last study drug administration.

   - Use of medications known to influence glucose tolerance.

   - Require use of other immunosuppressive agents.

   - Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B
   core antibody or surface antigen), or Hepatitis C infection.

   - Have serological evidence of current CMV infection.

   - Have evidence of active EBV infection.

   - Have any complicating medical issues or abnormal clinical laboratory results that
   interfere with study conduct or cause increased risk. These include pre-existing
   cardiac disease, COPD, neurological, or blood count abnormalities (such as
   lymphopenia, leukopenia, or thrombocytopenia).