Alemtuzumab Induction in Islet Transplantation

Inclusion Criteria: open to Canadians only participant must have had Type 1 diabetes mellitus for more than 5 years diabetes must be complicated by at least 1 of the following situations that persist despite intensive insulin management efforts: (1) Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 2 or more episodes of severe hypoglycemia requiring third party assistance within 12 months; or (2) Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 2 or more hospital visits for diabetic ketoacidosis over the last 12 months. Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent. Exclusion Criteria: Severe co-existing cardiac disease Active alcohol or substance abuse, to include cigarette smoking Psychiatric disorder making the subject not a suitable candidate for transplantation History of non-adherence to prescribed regimens Active infection including Hepatitis C, Hepatitis B, HIV, TB Any history of or current malignancies except squamous or basal skin cancer BMI > 28 kg/m2 at screening visit Creatinine clearance < 65 mL/min/1.73 m2 Blood creatinine > 150 µmol/L (1.7 mg/dL) Macroalbuminuria (urinary albumin excretion rate > 300 mg/24h) Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 130 g/L (<13 g/dL) in men Baseline screening liver function tests outside of normal range Untreated proliferative retinopathy Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding Previous transplant, or evidence of significant sensitization on PRA Insulin requirement >1.0 U/kg/day HbA1C >12% Uncontrolled hyperlipidemia Under treatment for a medical condition requiring chronic use of steroids Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5 Untreated Celiac disease Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy