Elevated Glycated Haemoglobin (HbA1c) Is Associated with an Increased Risk of Pancreatic Ductal Adenocarcinoma: A UK Biobank Cohort Study

SIMPLE SUMMARY: Pancreatic cancer is associated with a poor prognosis. This is often because it is diagnosed when it is too late for potentially curative treatment. There is an established link between raised blood sugars and pancreatic cancer. HbA1c is a blood test which provides clinicians with an average measurement of blood sugar over the past month. It is unclear what is the strength of the association between elevated HbA1c using the same parameters to diagnose prediabetes and diabetes, and if this association changes with length of follow up time. This study demonstrates that a HbA1c value consistent with a new diagnosis of diabetes (≥48 mmol/mol) is associated with a greater than eight fold risk of being diagnosed with pancreatic cancer in the next 12 months compared to a HbA1c in the normal range (<42 mmol/mol). ABSTRACT: Background: The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. Methods: A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42–47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. Results: PDAC occurred in 1157 participants during 11.6 (10.9–12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42–47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31–3.37, p = 0.002); and was 8.55 (4.58–15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. Conclusions: Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing.