Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

Inclusion Criteria: * Group 1: Diagnosis of Type-1 diabetes mellitus for more than 5 years with at least one of the following complications: * Metabolic lability/instability (two or more episodes of severe hypoglycemia) or two or more hospital visits for diabetic ketoacidosis during the previous year * Progression of secondary complications of diabetes as determined by The Nebraska Medical Center/University of Nebraska Medical Center staff endocrinologists * Group 2: Diagnosis of Type-1 diabetes with successful renal transplant on steroid-free, FK506/rapamycin-based immunosuppression Exclusion Criteria: * Severe co-existing cardiac disease * Active alcohol or substance abuse, including cigarette smoking * Psychiatric disorder making the subject not a suitable candidate for transplantation * History of medical non-compliance * Active infection, including hepatitis C and B, HIV, and tuberculosis (or suspected tuberculosis) * Any history of malignancy except squamous or basal cell skin cancer * BMI \>28 kg/meter-squared, or body weight \>80kg at screening visit, or \>85kg on the day of transplantation (due to the difficulty of obtaining a sufficiently large islet mass to adequately treat either large patients or those whose obesity elevates their insulin needs) * Positive C-peptide response to intravenous glucose tolerance test and Mixed Meal glucose tolerance test: any C-peptide \>0.3 ng/mL post infusion * Inability to provide informed consent * Age less than 19 or greater than 70 years * Creatinine clearance \<60 mL/min/1.73 meter-squared for Group 1 and creatinine clearance \<40 mL/min/1.73 meter-squared for Group 2 (those subjects currently on immunosuppression due to previous kidney transplant) * Macroalbuminuria (urinary albumin excretion rate \>300 mg/24h) for Group 1 and macroalbuminuria (urinary albumin excretion rate \>600mg/24h) for Group 2 * Baseline Hb \<10 gm/dL * Baseline liver function tests outside of normal range * Presence of gallstones or hemangioma in liver on baseline ultrasound exam * Positive pregnancy test, intention of future pregnancy, or presently breast-feeding * Evidence of sensitization on panel reactive antibodies (PRA) * Insulin requirement \>0.7 IU/kg/day or HbA1c \>15% * Hyperlipidemia * Under treatment for a medical condition requiring chronic use of steroids * Use of Coumadin or other anticoagulant therapy (except aspirin) or a prothrombin time/international normalized ratio (PT-INR) \>1.5 * Diagnosis of Addison's disease Additional Exclusion Criteria for Group 2 Subjects: * Any history of organ transplantation other than kidney or pancreas * Any previous graft lost to rejection * Any history of early, multiple, or vascular renal allograft rejection