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