PMID- 34990893
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20240210
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 75
DP  - 2022 Jan
TI  - Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: 
      Implications for earlier pancreatic cancer detection in new-onset diabetes.
PG  - 103802
LID - S2352-3964(21)00596-X [pii]
LID - 10.1016/j.ebiom.2021.103802 [doi]
LID - 103802
AB  - BACKGROUND: Screening for pancreatic ductal adenocarcinoma (PDAC) in populations 
      at high risk is recommended. Individuals with new-onset type 2 diabetes mellitus 
      (NOD) are the largest high-risk group for PDAC. To facilitate screening, we 
      sought biomarkers capable of stratifying NOD subjects into those with type 2 
      diabetes mellitus (T2DM) and those with the less prevalent PDAC-related diabetes 
      (PDAC-DM), a form of type 3c DM commonly misdiagnosed as T2DM. METHODS: Using 
      mass spectrometry- and immunoassay-based methodologies in a multi-stage analysis 
      of independent sample sets (n=443 samples), blood levels of 264 proteins were 
      considered using Ingenuity Pathway Analysis, literature review and targeted 
      training and validation. FINDINGS: Of 30 candidate biomarkers evaluated in up to 
      four independent patient sets, 12 showed statistically significant differences in 
      levels between PDAC-DM and T2DM. The combination of adiponectin and interleukin-1 
      receptor antagonist (IL-1Ra) showed strong diagnostic potential, (AUC of 0.91; 
      95% CI: 0.84-0.99) for the distinction of T3cDM from T2DM. INTERPRETATION: 
      Adiponectin and IL-1Ra warrant further consideration for use in screening for 
      PDAC in individuals newly-diagnosed with T2DM. FUNDING: North West Cancer 
      Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.
CI  - Crown Copyright (c) 2021. Published by Elsevier B.V. All rights reserved.
FAU - Oldfield, Lucy
AU  - Oldfield L
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Evans, Anthony
AU  - Evans A
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Rao, Rohith Gopala
AU  - Rao RG
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Jenkinson, Claire
AU  - Jenkinson C
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Purewal, Tejpal
AU  - Purewal T
AD  - Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, 
      UK.
FAU - Psarelli, Eftychia E
AU  - Psarelli EE
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Menon, Usha
AU  - Menon U
AD  - Institute of Clinical Trials and Methodology, University College London, UK.
FAU - Timms, John F
AU  - Timms JF
AD  - Women's Cancer, Institute for Women's Health, University College London, UK.
FAU - Pereira, Stephen P
AU  - Pereira SP
AD  - Institute for Liver and Digestive Health, University College London, UK.
FAU - Ghaneh, Paula
AU  - Ghaneh P
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Greenhalf, William
AU  - Greenhalf W
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Halloran, Christopher
AU  - Halloran C
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK.
FAU - Costello, Eithne
AU  - Costello E
AD  - Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 
      UK. Electronic address: ecostell@liverpool.ac.uk.
LA  - eng
GR  - G9901012/MRC_/Medical Research Council/United Kingdom
GR  - 26881/CRUK_/Cancer Research UK/United Kingdom
GR  - RG2014_01_PERERIA/PANCREATICCANUK_/Pancreatic Cancer UK/United Kingdom
GR  - 11883/CRUK_/Cancer Research UK/United Kingdom
GR  - 16186/CRUK_/Cancer Research UK/United Kingdom
GR  - 16812/CRUK_/Cancer Research UK/United Kingdom
GR  - 17680/CRUK_/Cancer Research UK/United Kingdom
GR  - 15957/CRUK_/Cancer Research UK/United Kingdom
GR  - G0801228/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_00004/01/MRC_/Medical Research Council/United Kingdom
GR  - 8968/CRUK_/Cancer Research UK/United Kingdom
GR  - 16791/CRUK_/Cancer Research UK/United Kingdom
GR  - 28210/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
DEP - 20220103
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (Adiponectin)
RN  - 0 (Biomarkers)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
SB  - IM
MH  - Adiponectin/blood
MH  - Biomarkers
MH  - *Carcinoma, Pancreatic Ductal/diagnosis
MH  - *Diabetes Mellitus, Type 2/diagnosis
MH  - Humans
MH  - Interleukin 1 Receptor Antagonist Protein/blood
MH  - *Pancreatic Neoplasms/diagnosis
PMC - PMC8741427
OTO - NOTNLM
OT  - Adiponectin
OT  - Blood biomarkers
OT  - Early detection
OT  - IL-1Ra
OT  - Pancreatic cancer
OT  - Type 3c diabetes
COIS- Declaration of Competing Interest LO, EC, WG, CH and PG are named as inventors on 
      GB patent GB1806002.0; PCT/GB2019/050998, submitted by the University of 
      Liverpool, that covers the measurement of adiponectin and IL-1Ra as a biomarker 
      for early detection of pancreatic cancer. UM holds patent number EP EP10178345.4 
      for breast cancer diagnosis, and has stock ownership awarded by the University 
      College London (UCL) in Abcodia.
EDAT- 2022/01/07 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/01/03
CRDT- 2022/01/06 20:18
PHST- 2021/09/17 00:00 [received]
PHST- 2021/12/20 00:00 [revised]
PHST- 2021/12/21 00:00 [accepted]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2022/01/06 20:18 [entrez]
PHST- 2022/01/03 00:00 [pmc-release]
AID - S2352-3964(21)00596-X [pii]
AID - 103802 [pii]
AID - 10.1016/j.ebiom.2021.103802 [doi]
PST - ppublish
SO  - EBioMedicine. 2022 Jan;75:103802. doi: 10.1016/j.ebiom.2021.103802. Epub 2022 Jan 
      3.