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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
1 Department of Endocrinology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, Grenoble, France. 2 Centre Hospitalier Universitaire Jean Minjoz, Service d'Endocrinologie-Métabolisme et Diabétologie-Nutrition, Besançon, France. 3 Hospices Civils de Lyon, Service de Néphrologie Médecine de la Transplantation et Immunologie clinique, Lyon, France. 4 Department of Nephrology, Pôle DigiDune, Grenoble University Hospital, Joseph Fourier University, Grenoble, France. 5 Hospices Civils de Lyon, Service d'Urologie et de Chirurgie de la Transplantation, Pôle Chirurgie, Lyon, France. 6 Hospices Civils de Lyon, Service d'Endocrinologie Diabète Nutrition, Lyon, France. 7 Centre Hospitalier de Montpellier, Pôle Rein Hypertension Métabolisme, Service d'Endocrinologie, Montpellier, France. 8 Centre Hospitalier Universitaire de Nancy, Service de Néphrologie, Nancy, France. 9 Hôpitaux Universitaires de Strasbourg, Service d'Endocrinologie Diabète et Maladies Métaboliques, Pôle NUDE, Strasbourg, France. 10 Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France. 11 Lyon University, EA Santé-Individu-Société, Lyon, France. 12 Address correspondence to: Sandrine Lablanche, Department of Endocrinology, CHU de Grenoble, BP217X, 38043 Grenoble, France.
Sandrine
S
Lablanche
Sophie
S
Borot
Olivier
O
Thaunat
Francois
F
Bayle
Lionel
L
Badet
Emmanuel
E
Morelon
Charles
C
Thivolet
Anne
A
Wojtusciszyn
Luc
L
Frimat
Laurence
L
Kessler
Alfred
A
Penfornis
Coralie
C
Brault
Cyrille
C
Colin
Domenico
D
Bosco
Thierry
T
Berney
Pierre Y
PY
Benhamou
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007330:Insulin Antibodies / Q000032:analysis / Q000502:physiology*; D007333:Insulin Resistance; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D001786:Blood Glucose; D007330:Insulin Antibodies