Pancreas
Gut. 2023;72(3):512–21
Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): A nested case-control study
Objective: Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk.
Design: The authors performed a population-based nested case-control study of 28,137 PDAC cases and 261,219 matched-controls in England. They described the associations of biomarkers with risk of PDAC using fractional polynomials and 5-year time trends using joinpoint regression. Associations with comorbidities and medication use were evaluated using conditional logistic regression.
Results: Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while following a U-shaped relationship for BMI and hemoglobin. Five-year trends showed biphasic BMI decrease and HbA1c increase prior to PDAC; early gradual changes 2–3 years prior, followed by late rapid changes 1–2 years prior. Liver markers and blood counts (white blood cell, platelets) showed monophasic rapid increase approximately 1 year prior. Recent diagnosis of pancreatic cyst, pancreatitis, type 2 diabetes and initiation of certain glucose-lowering and acid-regulating therapies were associated with highest risk of PDAC.
Conclusion: Risk of pancreatic ductal adenocarcinoma (PDAC) increased with raised HbA1c, liver markers, white blood cell and platelets, while followed a U-shaped relationship for body mass index (BMI) and hemoglobin. BMI and HbA1c derange biphasically approximately 3 years prior while liver markers and blood counts (white blood cell, platelets) derange monophasically approximately 1 year prior to PDAC. Profiling these in combination with their temporality could inform earlier PDAC diagnosis.