This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The success of pancreatic islet cell transplantation in animal models has culminated in the experimental procedure being performed in human type I diabetic human recipients. The outcome of clinical islet transplant has been variable, but more recently the majority of recipients are free from insulin therapy one year after transplantation. The avoidance of surgical complications through the percutaneous infusion of isolated islet cells into the liver promises a safer mode of transplantation and less need for post surgical care and hospitalization. The recent success of the University of Alberta when using new combinations of immunosuppressive drugs has led to new enthusiasm amongst transplant groups. This procedure, known as the Edmonton Protocol, has demonstrated improved success with a number of patients successfully remaining off insulin for over 3 years. The islet transplant protocol at the University of Virginia will focus on 3 groups of recipients, all with hypoglycemic unawareness. Non-uremic patients islet transplant alone (ITA), islet transplant after renal transplantation while patients are already taking immunosuppressants (IAK) and a simultaneous islet-kidney transplant in uremic patients (SIK). For all three groups of recipients, we hypothesize the close monitoring of islet function using continuous glucose monitoring techniques will allow early detection of islet dysfunction and more formal investigation (OGTT, IVGTT), which, if determined to be abnormal, will allow further diagnostic evaluation of donor specific reactivity and possible intervention such as exogenous insulin administration or the addition of more immunosuppression.