4.7 Article

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

Journal

EBIOMEDICINE
Volume 75, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ebiom.2021.103802

Keywords

Pancreatic cancer; Early detection; Type 3c diabetes; Blood biomarkers; Adiponectin; IL-1Ra

Funding

  1. North West Cancer Research, UK [CR1142]
  2. Cancer Research UK [C7690/A26881, C18616/A25153]
  3. Pancreatic Cancer Action, UK

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This study aimed to find a blood biomarker that can differentiate newly diagnosed type 2 diabetes mellitus (T2DM) patients into T2DM and PDAC-related diabetes. Through analysis of multiple sample sets, the researchers found that the combination of adiponectin and interleukin-1 receptor antagonist showed strong diagnostic potential for distinguishing T3cDM from T2DM.
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.

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