Impact of anti-insulin antibodies on islet transplantation outcome: data from the GRAGIL Network.

Abstract

In patients with type 1 diabetes, insulin antibodies (IA), altering the pharmacokinetics of circulating insulin, might be associated with high glucose concentration, prolonged hypoglycemia, and higher insulin requirement. The impact of IA on islet transplantation has never been explored. Our aim was to evaluate islet transplantation results at 1 year according to the presence of IA. Our work is a retrospective, case-control study, comparing IA-negative and IA-positive patients among the cohort of patients with type 1 diabetes transplanted within the Swiss-French GRAGIL network between 2003 and 2010. Data about IA were available for 17 patients. Before islet transplantation, 10 patients (59%) were screened positive for IA. At 12 months after transplantation, IA-positive patients reached insulin independence less frequently than IA-negative patients (cumulative incidence of insulin independence, 22.2% vs. 71.4%; P=0.02); β score was ≥7 in 43% of IA-negative patients versus 0% in IA-positive patients (P=0.022). When comparing IA-positive patients with IA-negative patients, insulin dose was 0.15 U/kg (0.10-0.18 U/kg) versus 0.01 U/kg (0-0.09 U/kg) (P=0.2); HbA1c was 6.1% (5.8%-6.3%) versus 6.1% (5.9%-6.8%) (P=0.16); basal C-peptide level was 460 ρmol/L (350-510 ρmol/L) versus 265 ρmol/L (177-405 ρmol/L) (P=0.28); occurrence of hypoglycemia was 12.5% versus 16.5% (P=0.9); and homeostatic model assessment insulin resistance was 1.25 (1-2.4) versus 0.7 (0.52-0.92) (P=0.01). After islet transplantation, IA-positive patients achieved insulin independence less frequently, exhibiting lower β score and higher homeostatic model assessment insulin resistance compared with IA-negative patients. However, in both groups, islet transplantation restored good glycemic control and drastically reduced hypoglycemia and insulin requirements.