Islet Cell Transplant for Type 1 Diabetes

Three different categories of patients with Type 1 Diabetes will be considered for study participation: * Naïve islet transplant alone (nITA) candidates: T1D patients complicated by frequent/severe hypoglycemia, hypoglycemia unawareness, AND/OR otherwise unstable blood glucose control who have not received a previous transplant (except for a failed pancreas more than 6 months prior to screening) * Repeat transplant (RT) candidates: T1D patients who have received two or fewer previous islet transplants \> 1 month prior to screening, but continue to require exogenous insulin treatment or have an HbA1c \> 6.5% * Islet after kidney transplant (IAK) candidates: T1D patients with a history of successful renal transplant \> 3 months prior to screening Inclusion criteria for all candidates: 1. Age 18-68 years 2. Type 1 diabetes mellitus for at least 5 years 3. Ability and willingness to comply with post-transplant regimen, including taking anti-rejection medications, use of reliable contraception, frequent clinic visits, lab tests, careful recording of blood glucose values, insulin doses and medications, and completing detailed follow-up studies Additional Inclusion Criteria nITA Candidates Only 4. Unstable blood sugar control characterized by: Frequent hypoglycemia (blood glucose ≤ 54 mg/dl more than once per week) -AND/OR- Hypoglycemia unawareness (Clarke score of 4 or more) -AND/OR- One or more severe hypoglycemic episodes in 12 months preceding enrollment. -AND/OR- Erratic blood glucose levels that interfere with daily activities -AND/OR- One or more hospital visits for diabetic ketoacidosis in the 12 months preceding enrollment Additional Inclusion Criteria for RT Candidates Only 5. One or two or previous islet transplants \> 1 month prior to screening with continuing insulin requirements and/or HbA1c \> 6.5% Additional Inclusion Criteria for IAK Candidates Only 6. Successful kidney transplant \> 3 months prior to screening 7. Stable maintenance immunosuppression consisting of tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic or azathoprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic +/- ≤ 10 mg/day corticosteroids 8. No history of acute rejection related to kidney graft in last 12 months and low risk of rejection 9. Under continuing care of physician for kidney graft, who has provided letter in support of candidate's consideration for study participation Exclusion Criteria: 1. Body Mass Index (BMI) \> 33 2. Insulin requirements \> 1.2 units/kg/day 3. Known sensitization to both rATG -and- alemtuzumab 4. Significant kidney dysfunction 5. Significant liver/gall bladder disease 6. Significant cardiovascular disease 7. Active proliferative retinopathy 8. High blood pressure despite appropriate treatment 9. High cholesterol/triglycerides despite appropriate treatment 10. Anemia or other blood disorders that require medical treatment 11. WBC \<3,000/ul 12. Increased risk of bleeding, other chronic hemostasis disorders, or treatment with chronic anticoagulant therapy 13. Recent unresolved acute infection (except for mild skin infection or nail fungal infection), or chronic infection 14. Epstein-Barr Virus (EBV) IgG negative 15. Any history of malignancy, except for completely resected squamous or basal cell carcinoma of the skin or in situ cancer of the cervix 16. Recent history of non-adherence to medical treatment, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin therapy 17. Psychiatric illness that is untreated, or likely to interfere significantly with study compliance despite treatment 18. Previous organ/tissue transplant, except as noted above 19. Administration of live attenuated vaccines within 2 months of enrollment 20. Presence of a chronic disease that must be chronically treated with a contraindicated agent 21. Use of investigational agents within four weeks of enrollment 22. Active alcohol or substance abuse, including cigarette smoking 23. Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures prior to study entry and for as long as they are on immunosuppression medication, and women presently breast feeding are excluded 24. Individuals without health insurance 25. History of gastric bypass 26. Any medical condition that in the opinion of the investigator will interfere with safe participation in the trial