Blood levels of adiponectin and IL-1Ra distinguish type 3c from type 2 diabetes: Implications for earlier pancreatic cancer detection in new-onset diabetes.

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.
Competing Interests: 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.
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