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 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 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