Inclusion Criteria:
* Patients must have type I diabetes mellitus, documented by undetectable C-peptide. Patients must have been diabetic for at least five years, and be aged 18 - 58 years.
* Patients must be on an intensive regimen of glucose monitoring and exogenous insulin injection (defined as greater than or equal to three checks and injections per day). This regimen must be prescribed and supervised by the patient's diabetologist.
* Despite intensive therapy, patients must have at least one of the following:
* Brittle diabetes (metabolic instability), as defined by elevated mean amplitude of glycemic excursion;
* Hypoglycemic unawareness, with at least one episode in the past two years in which hypoglycemia required the assistance of another person (e.g., family member, emergency medical technician \[EMT\], etc.), and was associated with a fingerstick blood glucose (FSBG) of \< 50 mg/dl and prompt recovery after administration of oral glucose, intravenous glucose, or glucagon;
* Progressive complications of diabetes (nephropathy manifested by proteinuria, retinopathy documented by an ophthalmologist after dilated eye exam, or neuropathy as determined by a neurologist).
* Patients must be able to give informed consent.
Exclusion Criteria:
* Failure to meet inclusion criteria
* Panel of Reactive Antibody (PRA) \> 10%
* Creatinine clearance \< 80 mL/min
* Prior organ transplant
* Portal hypertension: this refers to portal hypertension diagnosed previously by any means, or, by the investigators' evaluation, symptoms and/or signs of liver dysfunction with or without portal hypertension including, but not limited to, jaundice, ascites, encephalopathy, spider angiomata, coagulopathy, or peri-umbilical venous engorgement. Elevated portal pressures, as measured during intended islet infusion, may also result in discontinuation of infusion.
* Abnormal liver function tests (\> 2 times the upper limit of normal as defined by the University of Chicago Clinical Laboratory)
* History of malignancy. Any history of malignancy in a patient who has had an "adequate" period of no evidence of neoplastic disease should not rule out individuals from enrolling in this study. Rather, pre-enrollment screening for malignancy will follow current established guidelines as for solid-organ transplant. These current guidelines appear in Kasiske, B.L., et al. "The Evaluation of Renal Transplant Candidates: Clinical Practice Guidelines," American Journal of Transplantation 1 (Supplement 2): 12-22, 2001.
* Active peptic ulcer disease
* Pregnancy, or inability to comply with contraceptive regimen
* Severe unremitting gastroparesis or diarrhea
* Active infection
* Serologic positivity for HIV and/or hepatitis
* Chest radiographic abnormality consistent with neoplastic or infectious disease
* Major ongoing psychiatric illness and/or substance abuse
* Noncompliance with current medical regimen
* Obesity (body mass index \[BMI\] \> 28)
* Any other medical condition precluding safe transplantation and immunosuppression
* Ejection fraction \< 30%
* Myocardial infarction (MI) within the past 6 months
* Known allergies or hypersensitivity to immunosuppressive agents used in this protocol
* Inability to provide written informed consent.
