biostudies-literatureUnknownRickels MRNational Institute of Allergy and Infectious DiseasesNCATS NIH HHSNIDDK NIH HHSNCRR NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNIAID NIH HHSJuvenile Diabetes Research Foundation<h4>Objective</h4>To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia.<h4>Research design and methods</h4>This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin independence.<h4>Results</h4>Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c <7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation.<h4>Conclusions</h4>Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.Diabetes caredc212688https://www.ebi.ac.uk/biostudies/studies/S-EPMC9767903biostudies-literatureLong-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study.PMC9767903UL1 TR000150U01 DK085531U01DK085531UL1 TR0004541-SRA-2019-728-A-NU01DK070431U01DK070430U01 DK070460UL1 RR025741U01 AI089316U01 AI089317UL1 TR000460U01AI065193M01 RR000040U01AI065192U01AI065191UL1 TR000003U01 AI065193U01 AI065192UL1 TR000004U01 AI065191U01DK070460U01 DK070431M01 RR000400U01 DK070430U01AI089316UL1 TR000050U01AI089317Deng SStock PGMartellotto JHunsicker LGLuning-Prak EOnderka CYankey JZiaie ASWallia AToth LKorsgren ORobien MARyden MLundgren TMonson NDalton-Bakes CJasperson CDinyari PSchwieger TDillon JSBerne CWillits JOwen RMontelongo JAlvarez Gil AFoss APeterson KCagliero EMueller KIchii HAl-Saden PXu XAbdulla MHPriore ARickels MRRojas TShields BBrandenburg MMalcolm AGeorge LQi MLei JKaufman LFDBLarsen CPChaloner KFroud TInverardi LHutchinson JPosselt AMSarman DKissler HKandaswamy RNaji ASchneider EMcElroy JSears MHecyk ASzot GSchroeder AFeddersen DSzust JWilhelm JJImes SPawlick RCrisalli KCurry Corrales AAnsite JToth VSchneider KDiltz CEggerman TLGreen NMolitch MRamos MFu HMoreno JGranderson TBalamurugan ANTufveson GHering BJJenssen TDoelle GCLoganathan GPalanjian MOdorico JMin ZTurgeon NABrandhorst DWang LLafontant DEShapiro AMJNeill-Hudson TQidwai JHolbrook EBridges NDWang SKearns JO'Gorman DClarke WRRicordi CBegley BKamoun MChen XWang XWang YOberholzer JDanobeitia JSCzarniecki CWEcklund DJorns CShlansky-Goldberg RAlejandro RNathan DFoster ERyan EAPapas KKWebster DSenior PAvon Zur-MΕhlen BLi YFriiberg AStuart EKin TMarkmann EZitur LGilmore TBayman LClinical Islet Transplantation ConsortiumArreaza GMorrison YCarpentier SJohnson KRosichuk SLinetsky EFaradji RKenyon NKneteman NMBellin MDNilsson BQidwai JCErnst HKoh ABattle JBarbaro BWitson JZhai WFeurer IAvila JMcElvany KBigam DLPedersen JVivek KAlvarez ACampbell PKhan AKaufman DBRicher BHerrada ENollen DGoldstein JSPeixoto ECano JZhang XPutz GMarkmann JFLuo YLuo XLyon JLiu CChebleck PHarmon JVfalseLong-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study.<h4>Objective</h4>To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia.<h4>Research design and methods</h4>This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin independence.<h4>Results</h4>Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c <7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation.<h4>Conclusions</h4>Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.2022-01-01T00:00:00Z2022 Oct2025-04-04T09:50:16.933Z2025-02-19T01:17:40.731ZS-EPMC97679033625090510.2337/dc21-2688