Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes
Lucy Oldfield,
Anthony Evans,
Rohith Gopala Rao,
Claire Jenkinson,
Tejpal Purewal,
Eftychia E. Psarelli,
Usha Menon,
John F. Timms,
Stephen P. Pereira,
Paula Ghaneh,
William Greenhalf,
Christopher Halloran,
Eithne Costello
Affiliations
Lucy Oldfield
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Anthony Evans
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Rohith Gopala Rao
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Claire Jenkinson
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Tejpal Purewal
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, UK
Eftychia E. Psarelli
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Usha Menon
Institute of Clinical Trials and Methodology, University College London, UK
John F. Timms
Women's Cancer, Institute for Women's Health, University College London, UK
Stephen P. Pereira
Institute for Liver and Digestive Health, University College London, UK
Paula Ghaneh
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
William Greenhalf
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Christopher Halloran
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK
Eithne Costello
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, UK; Corresponding author at: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK.
Summary: 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.
