Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

Inclusion Criteria:

• Type 1 diabetes > 5 years complicated by at least one of the following situations despite intensive insulin management:

  • Reduced awareness of hypoglycemia at plasma glucose levels < 54 mg/dL
  • Metabolic lability/instability characterized by two or more episodes of severe hypoglycemia or hospital visits for diabetic ketoacidosis over the last year

  • Progressive secondary complications of diabetes:

    • Retinopathy—three step progression using the ETDRS grading system or equivalent progression;
    • Nephropathy— microalbuminuria rise of 50 µg/min (72 mg/24h) over three months within the past two years despite using an ACE inhibitor;
    • Neuropathy—persistent gastroparesis, postural hypotension, neuropathic bowel or bladder, or severe peripheral neuropathy unresponsive to management

Exclusion Criteria:

• Co-existing cardiac disease:

  • Myocardial infarction within past six months
  • Angiographic evidence of non-correctable coronary artery disease
  • Ischemia on functional cardiac exam d. Heart failure > NYHA II
• Active alcohol or substance abuse or cigarette smoking
• Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
• Non-adherence to prescribed regimens
• Active infection including hepatitis C, hepatitis B, HIV
• TB by history, current infection, or under treatment for suspected TB
• History of malignancies except squamous or basal skin cancer
• Stroke within the past 6 months
• BMI > 26 kg/m2 or body weight > 70 kg at screening visit
• C-peptide response to glucagon stimulation, any C-peptide ≥ 0.3 ng/mL
• Inability to provide informed consent
• Age less than 18 or greater than 65 years
• Creatinine clearance < 85 mL/min/1.73 m2 by 24-hour urine collection
• Serum creatinine > 1.5 mg/dL
• Macroalbuminuria > 300 mg/24h
• Baseline Hb < 12 gm/dL in women, < 13 gm/dL in men
• Baseline liver function tests outside normal range
• Untreated proliferative retinopathy
• Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast-feeding
• Previous transplant or PRA reactivity > 20%)
• Insulin requirement > 0.7 IU/kg/day
• HbA1C > 12%
• Hyperlipidemia
• Chronic use of steroids
• Use of coumadin or other anticoagulant (except aspirin) or PT INR > 1.5
• Addison's disease
• Allergy to radiographic contrast material