The objective of this study is to assess the safety and efficacy of islet allotransplantation for the reestablishment of stable glycemic control in patients with type 1 diabetes, using anti-thymocyte globulin induction immunosuppression with sirolimus, mycophenolate mofetil and low dose tacrolimus maintenance immunosuppression.

To assess the safety and efficacy of a new single-donor islet allotransplant protocol focusing on minimization of ischemic damage by the two-layer pancreas preservation technique, attenuation of posttransplant nonspecific inflammatory responses by etanercept and anti-thymocyte globulin, deletion/inactivation of autoreactive T cells by anti-thymocyte globulin and daclizumab induction immunotherapy, and potent yet non-diabetogenic maintenance immunosuppression with sirolimus and delayed mycophenolate mofetil instead of tacrolimus for the reestablishment of stable glycemic control in recipients with type 1 diabetes.

Inclusion Criteria:

1. Primary islet allotransplant

2. Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:

   1. Metabolic lability/instability;
   2. Reduced awareness of hypoglycemia;
   3. Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);
   4. Progressive secondary complications.

3. Age 18 and older

4. Able to give written informed consent

Exclusion Criteria:

1. Known hypersensitivity to rabbit proteins.
2. Presence of history of panel-reactive anti-HLA antibodies (>10%).
3. Insufficient cardiovascular reserve.
4. Creatinine clearance <60 mL/min/m2.
5. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease.
6. History of malignancy within 5 years.
7. Active peptic ulcer disease.
8. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
9. Pregnancy or breast-feeding.
10. Active infections.
11. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation.
12. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
13. Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening.
14. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications.
15. Ongoing substance abuse; drug or alcohol.
16. Recent history of noncompliance.
17. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.