Islet Transplantation in Type I Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol

Inclusion Criteria: * Eligible subjects must have Type 1 diabetes mellitus for more than 5 years, complicated by the following situations that persist despite intensive insulin management efforts: * At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person, and which was associated with either a blood glucose level \< 50 mg/dL (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration * Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at capillary glucose levels of \< 54 mg/dL (3 mmol/L) as reported by the subject Exclusion Criteria: * Diagnosis of co-existing cardiac disease characterized by any one of these conditions: * Recent myocardial infarction (within past six months), or * Angiographic evidence of non-correctable coronary artery disease, or * Evidence of ischemia on functional cardiac exam (with a stress echo test recommended * for subjects with a history of ischemic disease). * Heart failure \> New York Heart Assoication (NYHA) II * Active alcohol or substance abuse-includes cigarette smoking (must be abstinent for six months). Active alcohol abuse should be considered using the current National Institute on Alcohol Abuse and Alcoholism (NIAAA) definitions. * Psychiatric disorder making the subject not a suitable candidate for transplantation, e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication. (A psychological or psychiatric consultation is required only if considered necessary by some current indication or history.) * History of non-adherence to prescribed regimens * Active infection including hepatitis C, hepatitis B, HIV * TB (by history or currently infected as evidenced by a positive QuantiFERON® -TB Gold test or under treatment for suspected TB) * Any history of malignancies except squamous or basal skin cancer. Any subject found to have squamous or basal cancer is required to have it removed prior to transplant. * History of stroke within the past 6 months * Body Mass Index (BMI) \> 27 kg/m2. * C-peptide response to glucagon stimulation (1 mg i.v.) (any C-peptide ≥ 0.3 ng/mL) * Inability to provide informed consent * Age less than 18 or greater than 65 years * Creatinine clearance \< 80 mL/min/1.73 m2 by 24-hour urine collection. If corrected creatinine clearance is \< 80 and serum creatinine is \< 1.2 mg/dl, then a nuclear renal scan is required to determine gomerular filtration rate. * Serum creatinine consistently \> 1.5 mg/dL * Macroalbuminuria (urinary albumin excretion rate \> 300 mg/24h) * Baseline Hb \< 12 gm/dL in women or \< 13 gm/dL in men * Baseline liver function tests (LFT) outside of normal range (An initial LFT test panel with any values \> 1.5 times normal upper limits will exclude a subject without a re-test. A re-test for any values between normal and 1.5 times normal should be made, and if the values remain elevated above normal limits, the subject will be excluded.) * Untreated proliferative retinopathy * Positive pregnancy test, intent for future pregnancy, or male subjects' intent to procreate, unwilling to follow effective contraceptive measures, or presently breast-feeding * Insulin requirement \> 0.7 IU/kg/day * HbA1c \> 12% * Hyperlipidemia (fasting LDL cholesterol \> 130 mg/dL, treated or untreated; and/or fasting triglycerides \> 200 mg/dL) * Under treatment for a medical condition requiring chronic use of steroids other than a previous organ transplant * Use of coumadin or other antiplatelet or anticoagulant therapy, or subject with PT INR \> 1.5. Low dose aspirin is allowed after transplantation. * History of Factor V deficiency * Currently smoking tobacco * Addison's disease * Allergy to radiographic contrast material * Symptomatic cholecystolithiasis * Acute or chronic pancreatitis * Symptomatic peptic ulcer disease * Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications * Treatment with antidiabetic medication other than insulin within 4 weeks of enrollment * Use of any study medication within 4 weeks of enrollment * Received live attenuated vaccine(s) within 2 months of enrollment * Any medical condition that, in the opinion of the investigator, might interfere with safe participation