Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus

Inclusion Criteria: Patients between 18 and 65 years of age Patients with type 1 diabetes mellitus for more than 5 years duration One or more of the following: Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy Progressive complications of type 1 diabetes mellitus Body Mass Index (BMI) ≤26 Exclusion Criteria: Untreated proliferative diabetic retinopathy; HbA1C > 12%; Insulin requirement > 1.0u/kg/d Stimulated or basal C-peptide > 0.3 ng/ml Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl; Macroalbuminuria > 300mg albumin in 24 hours Presence of panel reactive antibodies > 20%; Previous/concurrent organ transplantation (except failed islet cell transplantation); Any medical condition requiring chronic use of steroids; Malignancy or previous malignancy (except non-melanomatous skin cancer); X-ray evidence of pulmonary infection; Active infections; Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided) Active peptic ulcer disease, Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound; Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence of vaccination), HTLV-1 or HCV; Negative serology for Epstein Barr virus (EBV) or evidence of acute infection (IgM>IgG); Abnormal liver function test; Anemia (hemoglobin <12.0 g/dl); Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides >200mg/dl and/or fasting LDL cholesterol>140mg/dl); Body Mass Index above 26 and/or weight >80kg; Prostate specific antigen (PSA) > 4 ng/ml; Unstable cardiovascular status (including positive stress echocardiography if >age 35); Active alcohol or substance abuse; Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable); Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate. Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant. History of previous transplant or previous bone marrow infusion. Persistent leucopenia (white blood cell count <3,000/mm3