Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus
Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus
We hypothesize that the following improvements to islet transplantation will increase the
 islet mass successfully isolated and allow for engraftment from a single pancreas. The
 improvements are:

 -  Using Two-Layer method preservation to improve pancreas quality before islet isolation

 -  Maintaining isolated islets in culture before transplantation

 -  Using a steroid-free immunosuppression regimen

 -  Transplanting the best combination of donor and recipient possible after HLA screening
 and final crossmatching
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