Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis

Aims: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycaemia in non-diabetic cancer patients is unclear. Materials and methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycaemia on overall survival, disease-free survival (DFS) or progression-free survival (PFS). Data from studies reporting a hazard ratio and 95% confidence interval and/or a P-value were pooled in a meta-analysis using generic inverse-variance and random effects modelling. Subgroup analyses were conducted based on method of hyperglycaemia measurement (HbA1c, other) and stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the hazard ratio for overall survival. Results: Twelve studies comprising a total of 9872 patients were included. All studies reported hazard ratios for overall survival. Three studies reported DFS; two reported PFS outcomes. Definitions of hyperglycaemia and cut-offs varied between studies. Hyperglycaemia was associated with worse overall survival (hazard ratio 2.05, 95% confidence interval 1.67–2.51; P \textless 0.001) and DFS (hazard ratio 1.98, 95% confidence interval 1.20–3.27; P = 0.007), but did not affect PFS (hazard ratio 1.08, 95% confidence interval 0.72–1.62; P = 0.71). The association with worse overall survival was maintained in subgroups based on method of hyperglycaemia measurement (subgroup difference P = 0.46) and stage (P = 0.14). Meta-regression showed a significantly greater magnitude of association between hyperglycaemia and decreased overall survival in studies with higher proportions of women and diabetic patients. Conclusions: Hyperglycaemia is associated with adverse overall survival and DFS in patients with cancer. The therapeutic role of glycaemic control in cancer patients warrants further investigation.