Blood glucose concentration and risk of pancreatic cancer: systematic review and dose-response meta-analysis

Abstract

Objective: To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer.

Design: Systematic review and dose-response meta-analysis of prospective observational studies.

Data sources: Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction.

Eligibility criteria: Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality.

Data extraction and synthesis: Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations.

Results: Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer.

Conclusions: Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer.

Fig 1 Flow chart of literature search for studies investigating association between blood glucose concentration and risk of pancreatic cancer

Fig 2 Summary rate ratio of pancreatic cancer, highest v lowest blood glucose category. Weights from random effects analysis. *Estimated from reported post-load blood glucose or haemoglobin A_1c concentrations. †Pooled from rate ratios for men and women. ‡Pooling of rate ratios for men and women not feasible because categorisation of blood glucose differed between sexes

Fig 3 Summary linear trend of rate ratio per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose. Weights from random effects analysis

Fig 4 Dose-response relation between fasting blood glucose and rate ratio for pancreatic cancer, showing point estimates and 95% confidence interval for non-linear analysis and point estimates for linear analysis. Circles indicate adjusted rate ratios in individual studies; size of bubble is proportional to precision (inverse of variance) of rate ratio

Fig 5 Dose-response relation between fasting blood glucose and rate ratio for pancreatic cancer, excluding categories with assigned fasting blood glucose concentration >7.0 mmol/L. Graph shows point estimates and 95% confidence interval for non-linear analysis and point estimates for linear analysis. Circles indicate adjusted rate ratios in individual studies; size of bubble is proportional to precision (inverse of variance) of rate ratio