PMID- 36201044
OWN - NLM
STAT- MEDLINE
DCOM- 20221215
LR  - 20230721
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 66
IP  - 1
DP  - 2023 Jan
TI  - Factors associated with favourable 5 year outcomes in islet transplant alone 
      recipients with type 1 diabetes complicated by severe hypoglycaemia in the 
      Collaborative Islet Transplant Registry.
PG  - 163-173
LID - 10.1007/s00125-022-05804-4 [doi]
AB  - AIMS/HYPOTHESIS: Islet transplantation has been studied in small cohorts of 
      recipients with type 1 diabetes complicated by severe hypoglycaemic events 
      (SHEs). We determined factors associated with favourable outcomes in a large 
      cohort of recipients reported to the Collaborative Islet Transplant Registry 
      (CITR). METHODS: In 398 non-uraemic islet transplant alone (ITA) recipients with 
      type 1 diabetes and SHEs, transplanted between 1999 and 2015 and with at least 1 
      year follow-up, we analysed specified favourable outcomes against each of all 
      available characteristics of pancreas donors, islet grafts, recipients and 
      immunosuppressive regimens, as well as immunosuppression and procedure-related 
      serious adverse events (SAEs). RESULTS: Four factors were associated with the 
      highest rates of favourable outcomes: recipient age >/=35 years; total infused 
      islets >/=325,000 islet equivalents; induction immunosuppression with T cell 
      depletion and/or TNF-alpha inhibition; and maintenance with both mechanistic target 
      of rapamycin (mTOR) and calcineurin inhibitors. At 5 years after the last islet 
      infusion, of the recipients meeting these four common favourable factors (4CFF; 
      N=126), 95% were free of SHEs, 76% had HbA(1c) <53 mmol/mol (7.0%), 73% had 
      HbA(1c) <53 mmol/mol (7.0%) and absence of SHEs, and 53% were insulin 
      independent, significantly higher rates than in the remaining recipients (<4CFF; 
      N=272). The incidence of procedural and immunosuppression-related SAEs per 
      recipient that resulted in sequelae, disability or death was low in both the 4CFF 
      (0.056 per person) and <4CFF (0.074 per person) groups. 
      CONCLUSIONS/INTERPRETATION: In recipients with type 1 diabetes complicated by 
      SHEs, islet transplantation meeting 4CFF protected 95% from SHEs at 5 years after 
      the last islet infusion and exerted a large and significant benefit on glycaemic 
      control, with an acceptable safety profile for this subgroup of type 1 diabetes.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Hering, Bernhard J
AU  - Hering BJ
AUID- ORCID: 0000-0002-5962-7284
AD  - Schulze Diabetes Institute and Department of Surgery, University of Minnesota, 
      Minneapolis, MN, USA. bhering@umn.edu.
FAU - Ballou, Cassandra M
AU  - Ballou CM
AUID- ORCID: 0000-0003-0097-5599
AD  - The EMMES Company, LLC, Rockville, MD, USA. cballou@emmes.com.
FAU - Bellin, Melena D
AU  - Bellin MD
AUID- ORCID: 0000-0002-7324-4837
AD  - Schulze Diabetes Institute and Department of Pediatrics, University of Minnesota, 
      Minneapolis, MN, USA.
FAU - Payne, Elizabeth H
AU  - Payne EH
AUID- ORCID: 0000-0003-0905-7647
AD  - The EMMES Company, LLC, Rockville, MD, USA.
FAU - Kandeel, Fouad
AU  - Kandeel F
AUID- ORCID: 0000-0003-3746-5015
AD  - Department of Clinical Diabetes, Endocrinology & Metabolism, City of Hope, 
      Duarte, CA, USA.
FAU - Witkowski, Piotr
AU  - Witkowski P
AUID- ORCID: 0000-0002-4459-6673
AD  - Pancreatic and Islet Transplant Program, Transplantation Institute, University of 
      Chicago, Chicago, IL, USA.
FAU - Alejandro, Rodolfo
AU  - Alejandro R
AUID- ORCID: 0000-0003-4387-5360
AD  - Diabetes Research Institute and Department of Medicine, University of Miami, 
      Miami, FL, USA.
FAU - Rickels, Michael R
AU  - Rickels MR
AUID- ORCID: 0000-0002-9253-838X
AD  - Institute for Diabetes, Obesity & Metabolism and Department of Medicine, 
      University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
FAU - Barton, Franca B
AU  - Barton FB
AUID- ORCID: 0000-0002-6628-5745
AD  - The EMMES Company, LLC, Rockville, MD, USA.
LA  - eng
GR  - U01 DK133709/DK/NIDDK NIH HHS/United States
GR  - UC4 DK114839/DK/NIDDK NIH HHS/United States
GR  - UC4 DK098086/DK/NIDDK NIH HHS/United States
GR  - R01 DK091331/DK/NIDDK NIH HHS/United States
GR  - P30 DK020595/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20221006
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
SB  - IM
MH  - Humans
MH  - Adult
MH  - *Diabetes Mellitus, Type 1
MH  - *Islets of Langerhans Transplantation/adverse effects
PMC - PMC10355148
MID - NIHMS1913167
OTO - NOTNLM
OT  - Clinical islet transplantation
OT  - Favourable factors
OT  - Severe hypoglycaemia
OT  - Type 1 diabetes
EDAT- 2022/10/07 06:00
MHDA- 2022/12/15 06:00
PMCR- 2023/07/19
CRDT- 2022/10/06 11:14
PHST- 2022/03/21 00:00 [received]
PHST- 2022/07/27 00:00 [accepted]
PHST- 2022/10/07 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/10/06 11:14 [entrez]
PHST- 2023/07/19 00:00 [pmc-release]
AID - 10.1007/s00125-022-05804-4 [pii]
AID - 10.1007/s00125-022-05804-4 [doi]
PST - ppublish
SO  - Diabetologia. 2023 Jan;66(1):163-173. doi: 10.1007/s00125-022-05804-4. Epub 2022 
      Oct 6.