Islet Transplantation for Type 1 Diabetes Mellitus

Inclusion Criteria:

• Duration of diabetes: 5 years or more
• Type 1 diabetes with C-peptide < 200 pmol/L and a simultaneous plasma glucose between 60 and 250 mg/dl
• Complex insulin program supervised by an endocrinologist for at least 6 months
• Hypoglycemic unawareness diagnosed using Clarke Awareness Questionnaire
• Body weight < 70 kg
• Body Mass Index < 30 kg/m^2
• Insulin requirement < 40 units/day by multiple daily injections or < 30 units /day by external insulin pump or < 0.6 unit/kg/day with a HbA1c < 7.0 % ( Normal < 6 %)
• No overt cardiovascular disease
• No laser treatment for retinopathy
• Retinopathy diagnosed by ophthalmologist to be stable and requiring no further evaluation for at least one year
• Women of child bearing age will have a negative pregnancy test at screening and time of trial initiation
• Women enrolled in the trial should be willing to practice birth control while on immunosuppression
• No psychologic issues that would interfere with adherence to safe clinical practice
• Blood type (ABO) compatibility
• No evidence of chronic liver disease (aspartate aminotransferase (AST) < 2.5 times normal, alanine aminotransferase (ALT) < 2.5 times normal, international normalized ratio (INR) < 1.4, No evidence of fatty liver on abdominal ultrasound.

Exclusion Criteria:

• Ongoing infection
• Ongoing alcohol or drug abuse
• Clinical portal hypertension
• Gall stones
• Liver hemangioma on ultrasound interfering with islet infusion
• Lack of updated immunization

• Unstable cardiovascular status as defined by:

  1. Myocardial infarction/acute coronary syndrome in last year
  2. Significant coronary atherosclerosis on angiography
  3. Active ischemia at evaluation
• Pre-trial low-density lipoprotein (LDL) cholesterol > 100 and triglycerides > 200 mg/dl with or without lipid lowering therapy
• Active peptic ulcer disease
• Previous organ transplantation except islet transplantation
• Negative serology for Epstein-Barr Virus (EBV) or ongoing acute EBV infection

• Previous malignancy unless

  1. 5 years ago
  2. basal cell cancer
  3. squamous cell cancer
• Requiring steroid therapy for any reason
• Positive Purified Protein Derivative (PPD - Tuberculosis Skin Test)
• Serological evidence of HIV, Hepatitis C or Hepatitis B
• Chronic anemia
• Single Antigen B (SAB) normalized value >1500

• Renal disease

  1. Iothalamate clearance < 70 cc/min
  2. 24 hour urine protein > 500 mg/24 hours