• Level of stimulated c-peptide at 90-minute derived from the mixed-meal tolerance test (MMTT) [ Time Frame: At 70 to 80 days after first islet transfusion ] [ Designated as safety issue: No ]
  

• Number of participants who achieve and maintain a 7.0% HbA1c level [ Time Frame: Throughout Study ] [ Designated as safety issue: No ]
  
• Number of severe hypoglycemic events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Percent reduction in insulin requirements, HbA1c level, mean amplitude of glycemic excursions, glycemic lability index, Clarke hypoglycemia awareness score, HYPO score, basal glucose and c-peptide, 90-minute glucose derived from MMTT, beta-score [ Time Frame: At 70 to 80 days after first islet transfusion ] [ Designated as safety issue: No ]
  
• C-peptide to glucose creatinine ratio, acute insulin response to glucose, insulin sensitivity, and FSIGT test, glucose variability and hypoglycemic duration derived from CGMS, proportion of participants with full islet graft function [ Time Frame: At 70 to 80 days after first islet transfusion ] [ Designated as safety issue: No ]
  
• Proportion of participants with full graft function, proportion of participants with an HbA1c < 7.0% and free of hypoglycemic events from day 28 through 365, percent reduction in insulin requirements [ Time Frame: At 350 to 379 days after the first and last islet transfusion ] [ Designated as safety issue: No ]
  
• HbA1c level, mean amplitude of glycemic excursions (MAGE), glycemic lability index (LI), Clarke hypoglycemia awareness score, HYPO score, basal glucose and c-peptide and 90-minute glucose derived from MMTT, beta-score [ Time Frame: At 350 to 379 days after the first and last islet transfusion ] [ Designated as safety issue: No ]
  
• C-peptide to glucose creatinine ratio, acute insulin response to glucose, insulin sensitivity, and FSIGT test, glucose variability and hypoglycemic duration derived from CGMS [ Time Frame: At 350 to 379 days after the first and last islet transfusion ] [ Designated as safety issue: No ]
  
• Proportion of participants receiving a second islet infusion, proportion of participants receiving a third islet transfusion [ Time Frame: At 350 to 379 days after the first and last islet transfusion ] [ Designated as safety issue: No ]
  
• Incidence and severity of adverse events related to islet infusion procedure, immunosuppression, immune sensitization, number of immunosuppression drug regimen changes [ Time Frame: At 70 to 80 days and 350 to 379 days after the first islet transfusion ] [ Designated as safety issue: Yes ]
  
• Incidence of worsening retinopathy [ Time Frame: At 350 to 379 days after the first islet transfusion ] [ Designated as safety issue: No ]
  

Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure and thus kidney transplant. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Rejection of these islets by the recipient's immune system, however, can make the treatment ineffective. An immune response known as instant blood-mediated inflammatory reaction (IBMIR) results in the disruption of islet integrity and islet loss within an hour of transfusion.

LMW-SD inhibits IBMIR by preventing the cascade that triggers it, when combined with pancreatic islets. The purpose of this study is to determine the safety and efficacy of LMW-SD given with islet transfusion and post-transfusion, along with immunosuppressive therapy, in people who have received kidney transplants.

This study will last for 1 year. Participants eligible for this study will have clinic visits every 3 months.

Once a preparation of islets becomes available, participants will be will be randomly assigned to Arm 1 or Arm 2.

Participants in Arm 1 will receive LMW-SD during and for 5 hours after transfusion. Participants in Arm 2 will heparin at the time of transfusion. All participants will also receive the oral medications, mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive intravenous daclizumab at time of transfusion and at Week 2, 4, 6, and 8 or intravenous basiliximab at the time of transplant and on Day 4. Transfusions will occur at the hospital and will be given intravenously. All participants will be eligible to receive second and third islet transfusions if previous transfusions fail. After each transfusion, study visits will occur on Days 1, 3, 7, 14, 21, 28, 75, and Months 6 and 12. At these visits, physical exams and blood collection will occur. At some visits urine collection will also occur.