337.6: Beta-cell function and insulin sensitivity with islet transplant alone and islet-after-kidney transplantation for type 1 diabetes in the Clinical Islet Transplantation (CIT) Consortium
Bibliographic record
Abstract
Clinical Islet Transplantation Consortium. Phase 3 studies of islet transplant alone (ITA)1 and islet-after-kidney (IAK)2 transplantation in type 1 diabetes were completed by the CIT Consortium using the same procedures for islet manufacturing and induction immunosuppression but differing in maintenance immunosuppression. Both studies met their criteria for safety and efficacy over 2 and 3 year planned follow-up, respectively. The insulin sensitivity index, SI, was derived from an insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test using the minimal model approach before (repeated annually) and after islet transplantation, with post-transplant tests also used to assess β-cell function from the acute insulin response to glucose (AIRg) and the disposition index (DI = AIRg · SI). Seventy subjects (48 ITA & 22 IAK) completed 79 tests before and 203 tests between 75 days and 3 years after islet transplantation. Time dependent impact of each parameter on hazard of islet graft failure defined by mixed-meal tolerance test stimulated C-peptide < 0.3 ng/mL was assessed by joint analysis (mixed model longitudinal & time-to-event). SI increased post-transplant in both cohorts and displayed an apparent hyperbolic relationship with post-transplant AIRg. Post-transplant SI was greater in ITA vs IAK (P < 0.001). Log-transformed AIRg and SI indicate that SI is ~24% lower at any given AIRg for IAK than ITA. Neither AIRg nor DI was significantly different between ITA and IAK post-transplant. Log-transformed AIRg and DI demonstrate significant prediction of islet graft failure such that each log increase of AIRg and DI reduces the hazard of islet graft failure by 45% and 42%, respectively. These results indicate that while insulin sensitivity improved after islet transplantation, post-transplant measures of β-cell function may better predict islet graft survival. Whether the differences in renal function between the cohorts or in maintenance immunosuppression (low-dose tacrolimus and sirolimus, ITA; tacrolimus and mycophenolic acid, IAK) may explain the greater insulin sensitivity in ITA vs IAK requires further study. This analysis was supported by grant 1-SRA-2019-728-A-N (to MRR and LGH) from the Juvenile Diabetes Research Foundation. The Clinical Islet Transplantation Consortium was supported by grants to the University of Pennsylvania (U01DK070430), University of Iowa (U01DK070431), University of Miami (U01DK070460), and University of California San Francisco (U01DK085531) from the National Institute of Diabetes and Digestive and Kidney Diseases, to the University of Alberta (U01AI065191), Uppsala University (U01AI065192), University of Minnesota (U01AI065193), Northwestern University (U01AI089316), and Emory University (U01AI089317) from the National Institute of Allergy and Infectious Diseases. References: 1. Hering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, Chaloner K, Czarniecki CW, Goldstein JS, Hunsicker LG, Kaufman DB, Korsgren O, Larsen CP, Luo X, Markmann JF, Naji A, Oberholzer J, Posselt AM, Rickels MR, Ricordi C, Robien MA, Senior PA, Shapiro AMJ, Stock PG, Turgeon NA: Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 39(7): 1230-1240, July 2016. PMCID: PMC5317236 2. Markmann JF, Rickels MR, Eggerman TL, Bridges ND, Lafontant DE, Qidwai J, Foster E, Clarke WR, Kamoun M, Alejandro R, Bellin M, Chaloner K, Czarniecki CW, Goldstein JS, Hering BJ, Hunsicker LG, Kaufman DB, Korsgren O, Larsen CP, Luo X, Naji A, Oberholzer J, Posselt AM, Ricordi C, Senior PA, Shapiro AMJ, Stock PG, Turgeon NA; Clinical Islet Transplantation Consortium: Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. American Journal of Transplantation 21(4): 1477-1492, April 2021. PMCID: PMC9074710
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".