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

Abstract

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.

Fig 1. Study participants, a consort diagram illustrating the construction of the case-control dataset and plan of the analysis to fulfil the aims and objectives of this study.

Fig 2. Longitudinal plots, BMI and HbA1c over time from six years before pancreatic cancer diagnosis up to a year after diagnosis.

A) total sample, B) and C) subgroup analysis: B) by diabetes status and C) by gender. Raw monthly averages are presented with the grey continuous line. Smoothed trends over time are obtained by fitting changes in BMI and HbA1c as a function of time with linear regression and a three-knot cubic spline to allow non-linearity.

Fig 3. Adjusted odds ratios and 95% confidence intervals for the association of pancreatic cancer with a 1 kg/m2 decrease in body mass index (BMI) between cases and controls (blue circles) and a 1 mmol/mol increase in glycated haemoglobin (HbA1c) (green squares) from 5 years before pancreatic cancer diagnosis.

The top plot is for the total study sample. The two further plots show subgroup analysis by the diabetes status.