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

Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycaemia in non-diabetic cancer patients is unclear.

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.

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 < 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.

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.