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Cited by 64Pancreatic function and diabetesDiabetes and associated disordersDiabetes Management and Research

Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 patients from the Collaborative Islet Transplant Registry

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Chetboun, Mikaël, Drumez, Elodie, Ballou, Cassandra, Maanaoui, Mehdi, Payne, Elizabeth, Barton, Franca, Kerr-Conte, Julie, Vantyghem, Marie-Christine +72 more·2023·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(23)00082-7PMC PMC10388704
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Abstract

Background Allogeneic islet transplantation is a validated therapy in type 1 diabetes; however, there is decline of transplanted islet graft function over time and the mechanisms underlying this decline are unclear. We evaluated the distinct association between primary graft function (PGF) and 5-year islet transplantation outcomes. Methods In this retrospective, multicentre, observational cohort study, we enrolled all patients from the Collaborative Islet Transplant Registry who received islet transplantation alone (ITA recipients) or islet-after-kidney transplantation (IAK recipients) between Jan 19, 1999, and July 17, 2020, with a calculable PGF (exposure of interest), measured 28 days after last islet infusion with a validated composite index of islet graft function (BETA-2 score). The primary outcome was cumulative incidence of unsuccessful islet transplantation, defined as an HbA 1c of 7·0% (53 mmol/mol) or higher, or severe hypoglycaemia (ie, requiring third-party intervention to correct), or a fasting C-peptide concentration of less than 0·2 ng/mL. Secondary outcomes were graft exhaustion (fasting C-peptide <0·3 ng/mL); inadequate glucose control (HbA 1c ≥7·0% [53 mmol/mol] or severe hypoglycaemia); and requirement for exogenous insulin therapy (≥14 consecutive days). Associations between PGF and islet transplantation outcomes were explored with a competing risk analysis adjusted for all covariates suspected or known to affect outcomes. A predictive model based on PGF was built and internally validated by using bootstraps resampling method. Findings In 39 centres worldwide, we enrolled 1210 patients with a calculable PGF (of those without missing data, mean age 47 years [SD 10], 712 [59·5%] were female, and 865 (97·9%) were White), who received a median of 10·8 thousand islet-equivalents per kg of bodyweight (IQR 7·4-13·5). 986 (82·4%) were ITA recipients and 211 (17·6%) were IAK recipients. Of 1210 patients, 452 (37·4%) received a single islet infusion and 758 (62·6%) received multiple islet infusions. Mean PGF was 14·3 (SD 8·8). The 5-year cumulative incidence of unsuccessful islet transplantation was 70·7% (95% CI 67·2-73·9), and was inversely and linearly related to PGF, with an adjusted subhazard ratio (sHR) of 0·77 (95% CI 0·72-0·82) per 5-unit increase of BETA-2 score (p<0·0001). Secondary endpoints were similarly related to PGF. The model-adjusted median C-statistic values of PGF for predicting 5-year cumulative incidences of unsuccessful islet transplantation, graft exhaustion, inadequate glucose control, and exogenous insulin therapy were 0·70 (range 0·69-0·71), 0·76 (0·74-0·77), 0·65 (0·64-0·66), and 0·72 (0·71-0·73), respectively. Interpretation This global multicentre study reports a linear and independent association between PGF and 5-year clinical outcomes of islet transplantation. The main study limitations are its retrospective design and the absence of analysis of complications. Funding Public Health Service Research, National Institutes of Health, Juvenile Diabetes Research Foundation International, Agence National de la Recherche, Fondation de l'Avenir, and Fonds de Dotation Line Renaud-Loulou Gasté.

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  • Controlled trials and follow-up of recipients in major centres showed that high rates of insulin independence can be reached, and long duration of graft function is also seen.

    “Controlled trials 62,63 and followup of recipients 64,65 in major centres showed that high rates of insulin independence can be reached, and long duration of graft function is also seen; however,”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [64]

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  1. [19]Ryan EA, Paty BW, Senior PA, Lakey JRT, Bigam D, Shapiro AMJ. β-Score An assessment of β-cell function after islet transplantation. Diabetes Care 2005; 28: 343– 7. 15677790
  2. [29]Rubin DB. Multiple Imputation for Nonresponse in Surveys, Subsequent édition. Hoboken, N.J: Wiley-Interscience, 2004.

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Authors
Chetboun, M., Drumez, E., Ballou, C., Maanaoui, M., Payne, E., Barton, F., Kerr-Conte, J., Vantyghem, M.-C., Piemonti, L., Rickels, M. R., Labreuche, J., Pattou, F., Alejandro, R., Aull, M., Bellin, M., Berney, T., Borja-Cacho, D., Brayman, K., Cagliero, E., Caiazzo, R., Cattral, M., Coates, T., Danielson, K., Defrance, F., De Koning, E., Desai, C., Desai, N., Gaber, A. O., Gmyr, V, Gores, P., Goss, J. A., Gottllieb, P., Greenbaum, C., Hardy, M., Harlan, D., Hering, B., Kandeel, F., Kaufman, D., Kay, T., Keymeulen, B., Khan, K., Kudva, Y., Larsen, C., Le Mapihan, K., Levy, G., Levy, M., Loudovaris, T., Lundgren, T., Maffi, P., Markmann, J., Marks, W. H., Naji, A., O'Connell, P., Oberholzer, J., Odorico, J., Onaca, N., Pattou, F., Piemonti, L., Pipeleers, D., Posselt, A., Rajab, A., Raverdy, V, Rickels, M. R., Ricordi, C., Rossini, A. A., Saudek, F., Schrope, B., Secchi, A., Senior, P., Shapiro, A. M. J., Shaw, J., Stock, P., Thomas, D., Thompson, M. J., Vantyghem, M. C., Vargas, L., Wang, H., Wiseman, A., Witkowski, P., & Yoon, K.
Affiliations
  • Inserm (FR)
  • Emmes (United States) (US)
  • IRCCS Ospedale San Raffaele (IT)
  • Hospital of the University of Pennsylvania (US)
  • Centre Hospitalier Universitaire de Lille (FR)
Corresponding author
Pattou, François
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2023-06
Volume
11
Issue
6
Pages
391-401
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(23)00082-7
PMC
PMC10388704
OpenAlex
W4366817838
Cited by
64
References
30
Citations by year
2026: 13 · 2025: 24 · 2024: 19 · 2023: 8
FWCI
17.15
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Diabetes & Endocrinology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by-nc-nd)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
  • HAL (submittedVersion)
Funders
  • National Institutes of Health (UC4 DK114839, UCH DK098086)
  • Juvenile Diabetes Research Foundation International (R01 DK091331)
  • U.S. Public Health Service
  • Fondation de l'Avenir pour la Recherche Médicale Appliquée
  • Agence Nationale de la Recherche (ANR-10-LABX-46)
  • Institut National de la Santé et de la Recherche Médicale
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
primary graft function, type 1 diabetes, islet transplantation outcomes, hypoglycemia, HbA1c, C-peptide
MeSH terms
Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Insulin, Male, Middle Aged, Registries, Retrospective Studies, Transplantation, Homologous, Islets of Langerhans Transplantation, Treatment Outcome

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