Lablanche S, et al. - In this multicenter, open-label, randomized controlled trial, researchers evaluated the effectiveness and safety of islet transplantation vs insulin therapy in patients with type 1 diabetes with severe hypoglycemia or following kidney transplantation. They found that metabolic outcomes were effectively improved by islet transplantation. For patients with severe, unstable type 1 diabetes who were not responding to intensive medical treatments, islet transplantation appeared to be a solid alternative. Knowing that immunosuppression could affect kidney function, careful selection of patients is needed.

Methods

• For this investigation, the researchers randomly assigned (1:1) subjects with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation).
• Participants in the study were aged 18–65 years and had severe hypoglycemia or hypoglycemia unawareness, or kidney grafts with poor glycemic control.
• Computer-generated randomization was used, stratified by center and type of patient.
• Islet recipients were scheduled to receive 11,000 islet equivalents per kg bodyweight in one to three infusions.
• Proportion of patients with a modified β-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months following the first islet infusion in the immediate transplantation group or 6 months after randomization in the insulin group was the primary outcome.
• The primary analysis included all subjects who received the allocated intervention.
• Safety was assessed in all subjects who received islet infusions.

Results

• Between July 8, 2010 and July 29, 2013, 26 were randomly assigned to immediate islet transplantation and 24 to insulin treatment, of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention.
• In the immediate transplantation group, median follow-up was 184 days (IQR 181–186) and in the insulin therapy group, median follow-up was 185 days (172–201).
• It was noted that 16 (64% [95% CI 43–82]) of 25 subjects in the immediate islet transplantation group had a modified β-score of 6 or higher vs none (0% [0–15]) of the 22 patients in the insulin group (p < 0.0001) at 6 months.
• Findings revealed that bleeding complications had occurred in four (7% [2–18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90.5 mL/min (IQR 76.6–94.0) to 71.8 mL/min (59.0–89.0) was seen in islet recipients who had not previously received a kidney graft and from 63.0 mL/min (55.0–71.0) to 57.0 mL/min (45.5–65.1) in islet recipients who had previously received a kidney graft, at 12 months after first infusion.