PMID- 37650380
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240418
IS  - 1399-0012 (Electronic)
IS  - 0902-0063 (Print)
IS  - 0902-0063 (Linking)
VI  - 37
IP  - 12
DP  - 2023 Dec
TI  - Islet graft function by mixed meal tolerance testing is sustained over 4 years in 
      young children undergoing total pancreatectomy with islet autotransplantation.
PG  - e15106
LID - 10.1111/ctr.15106 [doi]
AB  - Children with intractable chronic pancreatitis may require total pancreatectomy 
      with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the 
      severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance 
      tests (MMTT) in 134 children undergoing TPIAT to determine whether superior 
      survival of islet grafts explains higher rates of insulin independence previously 
      reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, 
      age 12-18 years). For MMTT, children consumed Boost HP and we sampled C-peptide 
      and glucose repeatedly over 2 h. The trajectory of outcomes before and after 
      TPIAT was compared between children and adolescents using data from pre-TPIAT and 
      3, 6 months, 1, 2, 3, and 4 years post-TPIAT and mixed linear models with a 
      random effect for child. Cox regression was used to analyze time outcomes (e.g., 
      time to first off insulin). Islet mass transplanted, measured as islet 
      equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in 
      young children (p < .001) because of their lower weight. AUC C-peptide in young 
      children increased somewhat over 4 years, but was stable in adolescents 
      (p = .0013). AUC glucose increased more in adolescents over time post-TPIAT 
      (p = .0024). Islet function by AUC C-peptide:AUC glucose ratio was better 
      preserved in young children (p < .001). Adolescents were less likely to wean off 
      insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of 
      young age in islet graft survival after TPIAT. The greater likelihood of insulin 
      independence in young children may be driven by better islet survival after 
      transplant.
CI  - (c) 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.
FAU - Gnikpingo, Taylor
AU  - Gnikpingo T
AD  - Departments of Pediatrics, Minneapolis, USA.
FAU - Benson, Sydney
AU  - Benson S
AD  - Department of Biostatistics, School of Public Health, University of Minnesota, 
      Minneapolis, USA.
FAU - Hodges, James S
AU  - Hodges JS
AUID- ORCID: 0000-0001-7467-6941
AD  - Department of Biostatistics, School of Public Health, University of Minnesota, 
      Minneapolis, USA.
FAU - Downs, Elissa
AU  - Downs E
AUID- ORCID: 0000-0001-5145-6903
AD  - Departments of Pediatrics, Minneapolis, USA.
FAU - Cook, Marie
AU  - Cook M
AD  - Departments of Pediatrics, Minneapolis, USA.
FAU - Schwarzenberg, Sarah J
AU  - Schwarzenberg SJ
AUID- ORCID: 0000-0001-5077-7625
AD  - Departments of Pediatrics, Minneapolis, USA.
FAU - Chinnakotla, Srinath
AU  - Chinnakotla S
AUID- ORCID: 0000-0002-5443-1258
AD  - Departments of Pediatrics, Minneapolis, USA.
AD  - Surgery, University of Minnesota Medical School and University of Minnesota 
      Masonic Children's Hospital, Minneapolis, USA.
FAU - Bellin, Melena D
AU  - Bellin MD
AUID- ORCID: 0000-0002-7324-4837
AD  - Departments of Pediatrics, Minneapolis, USA.
AD  - Surgery, University of Minnesota Medical School and University of Minnesota 
      Masonic Children's Hospital, Minneapolis, USA.
LA  - eng
GR  - UL1 TR002494/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230831
PL  - Denmark
TA  - Clin Transplant
JT  - Clinical transplantation
JID - 8710240
RN  - 0 (C-Peptide)
RN  - 0 (Insulin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Child
MH  - Adolescent
MH  - Humans
MH  - Child, Preschool
MH  - Transplantation, Autologous
MH  - *Islets of Langerhans Transplantation
MH  - Pancreatectomy
MH  - C-Peptide
MH  - Insulin
MH  - Glucose
MH  - Treatment Outcome
PMC - PMC10841198
MID - NIHMS1926130
OTO - NOTNLM
OT  - MMTT
OT  - TPIAT
OT  - autoislet
OT  - diabetes
OT  - pancreatectomy
OT  - pancreatitis
OT  - type 3c diabetes
COIS- Conflicts of Interest: MDB discloses advisory roles for Ariel Precision Medicine, 
      Insulet, Vertex, and research support from Dexcom and Viacyte.
EDAT- 2023/08/31 06:42
MHDA- 2023/12/17 09:43
PMCR- 2024/12/01
CRDT- 2023/08/31 05:53
PHST- 2023/07/31 00:00 [revised]
PHST- 2023/06/06 00:00 [received]
PHST- 2023/08/14 00:00 [accepted]
PHST- 2024/12/01 00:00 [pmc-release]
PHST- 2023/12/17 09:43 [medline]
PHST- 2023/08/31 06:42 [pubmed]
PHST- 2023/08/31 05:53 [entrez]
AID - 10.1111/ctr.15106 [doi]
PST - ppublish
SO  - Clin Transplant. 2023 Dec;37(12):e15106. doi: 10.1111/ctr.15106. Epub 2023 Aug 
      31.