Improvement in outcomes of clinical islet transplantation: 1999-2010

Abstract

Objective: To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010.

Research design and methods: A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999-2002), mid (2003-2006), or recent (2007-2010) transplant era based on annual follow-up to 5 years.

Results: Insulin independence at 3 years after transplant improved from 27% in the early era (1999-2002, n = 214) to 37% in the mid (2003-2006, n = 255) and to 44% in the most recent era (2007-2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA(1c) and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007-2010 vs. 60-65% in 1999-2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001).

Conclusions: The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007-2010 compared with those in 1999-2006, with fewer islet infusions and adverse events per recipient.

Figure 1

Islet allograft recipients (N = 677) registered in CITR according to type of transplant (n per year; top), induction immunosuppression at first infusion (% by year; center), and maintenance immunosuppression at first infusion (% by year; bottom). ITA, islet transplant alone.

Figure 2

A: Rates of insulin independence after allogeneic islet infusion (islet transplant alone and IAK), annually after last infusion. Left: By era (P = 0.02). Right: By induction immunosuppression category (P < 0.01). B: Durability of graft function (basal C-peptide ≥0.3 ng/mL) after the last infusion, by era (P < 0.001; left). The immediate drop at time 0 is occurrences of primary nonfunction (i.e., C-peptide never ≥0.3 ng/mL). In the most recent era, 95% of those who ever achieved insulin independence (II) retained graft function through 3 years after last infusion compared with 70% for those who never achieved II (P < 0.001; right). C: Percentage of patients with HbA_1c <6.5% or drop by two percentage points (P = 0.03; left); and absence of severe hypoglycemic events regardless of complete graft failure (P = NS by era; there were insufficient data from 2007–2010; right). D: The percentage with HbA_1c <6.5% or drop by 2% increases with increasing C-peptide level (P < 0.001; left), as does absence of severe hypoglycemic events (P < 0.001; right), annually after the last infusion. (A high-quality color representation of this figure is available in the online issue.)

Figure 3

A: Mortality by era (P = 0.49). B: Life-threatening events by era (P = 0.01). C: Incidence of any adverse event (AE) in year 1 of first infusion (P = 0.02 by era). D: CKD-EPI calculated glomerular filtration rate, by era.