Determining the feasibility of calculating pancreatic cancer risk scores for people with new-onset diabetes in primary care (DEFEND PRIME): study protocol.

INTRODUCTION: Worldwide, pancreatic cancer has a poor prognosis. Early diagnosis may improve survival by enabling curative treatment. Statistical and machine learning diagnostic prediction models using risk factors such as patient demographics and blood tests are being developed for clinical use to improve early diagnosis. One example is the Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) model, which employs patients' age, blood glucose and weight changes to provide pancreatic cancer risk scores. These values are routinely collected in primary care in the UK. Primary care's central role in cancer diagnosis makes it an ideal setting to implement ENDPAC but it has yet to be used in clinical settings. This study aims to determine the feasibility of applying ENDPAC to data held by UK primary care practices. METHODS AND ANALYSIS: This will be a multicentre observational study with a cohort design, determining the feasibility of applying ENDPAC in UK primary care. We will develop software to search, extract and process anonymised data from 20 primary care providers' electronic patient record management systems on participants aged 50+ years, with a glycated haemoglobin (HbA1c) test result of ≥48 mmol/mol (6.5%) and no previous abnormal HbA1c results. Software to calculate ENDPAC scores will be developed, and descriptive statistics used to summarise the cohort's demographics and assess data quality. Findings will inform the development of a future UK clinical trial to test ENDPAC's effectiveness for the early detection of pancreatic cancer. ETHICS AND DISSEMINATION: This project has been reviewed by the University of Surrey University Ethics Committee and received a favourable ethical opinion (FHMS 22-23151 EGA). Study findings will be presented at scientific meetings and published in international peer-reviewed journals. Participating primary care practices, clinical leads and policy makers will be provided with summaries of the findings.

BMI and HbA1c are metabolic markers for pancreatic cancer: Matched case-control study using a UK primary care database.

BACKGROUND: Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and their association with pancreatic cancer from five years before diagnosis. METHODS: A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status. RESULTS: Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04). CONCLUSIONS: The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.