Inclusion Criteria:  Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third-party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI >400/>300. Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and/or 1 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:  Significant skin conditions involving the area(s) targeted for implantation. Examples include but are not limited to recurrent boils/furuncles, extensive surgery or scarring, or lipodystrophy. History of enrollment in any other islet transplant trials and islet transplant under standard of care (at the discretion of the investigator). Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction <30%; or (c) evidence of ischemia on functional cardiac exam. Active alcohol or substance abuse, including cigarette smoking (must be abstinent for 6 months prior to listing for transplant). 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). History of non-adherence to prescribed regimens. Active infection including Hepatitis C, Hepatitis B, HIV, or TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis). Any history of, or current malignancies except squamous or basal skin cancer. BMI > 35 kg/m2 at screening visit. Age less than 18 or greater than 68 years. Measured glomerular filtration rate (GFR) <60 mL/min/1.73 m2. Presence or history of macroalbuminuria (>300 mg/g creatinine). Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months). Baseline Hb < 105 g/L (<10.5 g/dL) in women, or < 120 g/L (<12 g/dL) in men. Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values >1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded. 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. Evidence of significant sensitization on PRA (at the discretion of the investigator). Insulin requirement >1.0 U/kg/day HbA1C >12%.