Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes.
Adiponectin
Blood biomarkers
Early detection
IL-1Ra
Pancreatic cancer
Type 3c diabetes
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
17
09
2021
revised:
20
12
2021
accepted:
21
12
2021
pubmed:
7
1
2022
medline:
1
4
2022
entrez:
6
1
2022
Statut:
ppublish
Résumé
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. 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. 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. Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM. North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
Adiponectin and IL-1Ra warrant further consideration for use in screening for PDAC in individuals newly-diagnosed with T2DM.
FUNDING
BACKGROUND
North West Cancer Research, UK, Cancer Research UK, Pancreatic Cancer Action, UK.
Identifiants
pubmed: 34990893
pii: S2352-3964(21)00596-X
doi: 10.1016/j.ebiom.2021.103802
pmc: PMC8741427
pii:
doi:
Substances chimiques
Adiponectin
0
Biomarkers
0
Interleukin 1 Receptor Antagonist Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103802Subventions
Organisme : Medical Research Council
ID : G9901012
Pays : United Kingdom
Organisme : Pancreatic Cancer UK
ID : RG2014_01_PERERIA
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 11883
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00004/01
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 8968
Pays : United Kingdom
Informations de copyright
Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
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.