MGA031, Sirolimus and Tacrolimus in Islet Transplantation

Inclusion Criteria: 1. Age 18 to 65 years of age. 2. Ability to provide written informed consent. 3. Mentally stable and able to comply with the procedures of the study. 4. Clinical history compatible with type 1 diabetes with onset of disease at \<40 years of age and insulin-dependence for \> 5 years at the time of enrollment. 5. Absent stimulated C-peptide (\<0.3ng/ml) in response to a mixed meal tolerance test. 6. Involvement in intensive diabetes management defined as self monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the previous 12 months. 7. At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person and which was associated with either a blood glucose level \< 50 mg/dl or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration). 8. Reduced awareness of hypoglycemia. Exclusion Criteria: 1. Any previous transplant. 2. BMI \>27 kg/m2 or patient weight ≤ 50kg. 3. Insulin requirement of \> 0.8 IU/kg/day or 50 IU/day. 4. HbA1c \>10%. 5. Untreated proliferative diabetic retinopathy. 6. Uncontrolled Hypertension. 7. Estimated glomerular filtration rate \<70 ml/min/1.73 m2 for females and \<80 ml/min/1.73 m2 for males 8. Presence or history of macroalbuminuria (\>300mg/d). 9. Presence or history of panel-reactive anti-HLA antibodies \>20% by flow cytometry. 10. Females: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. Males: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception. 11. Active infection. 12. Negative screen for Epstein-Barr Virus (EBV). 13. Invasive aspergillus infection within one year prior to study entry. 14. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin. 15. Active alcohol, tobacco or substance abuse. 16. Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia, neutropenia, or thrombocytopenia. 17. A history of Factor V deficiency. 18. Any coagulopathy or medical condition requiring long-term anticoagulant therapy. 19. Severe co-existing cardiac disease. 20. Persistent elevation of liver function tests. 21. Symptomatic cholecystolithiasis. 22. Acute or chronic pancreatitis. 23. Symptomatic peptic ulcer disease. 24. Unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with absorption. 25. Hyperlipidemia despite medical therapy (fasting LDL cholesterol \> 130 mg/dl, treated or untreated; and/or fasting triglycerides \> 200 mg/dl). 26. Chronic use of systemic steroids. 27. Use of any other investigational agents within 4 weeks of participation. 28. Administration of live attenuated vaccine(s) within 2 months of enrollment. 29. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.