Glycosylated haemoglobin and prognosis in 10,536 people with cancer and pre-existing diabetes: a meta-analysis with dose-response analysis

Aims To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. Methods In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA(1c)) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA(1c) or per 1-unit HbA(1c) increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. Results Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA(1c) >= 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03-1.27]; p-value: 0.012), cancer-specific mortality (5; 1.68 [1.13-2.49]; p-value: 0.011) and cancer recurrence (8; 1.68 [1.18-2.38; p-value: 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA(1c) (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01-1.08]; p-value: 0.016) and cancer-specific mortality (4; 1.11 [1.04-1.20]; p-value: 0.003). All RRs were attenuated in trim-and-fill analyses. Conclusions Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control.

Automated summary

This study assessed the association between glycemic control and prognosis in cancer patients with pre-existing diabetes. Fifteen eligible observational studies involving 10,536 patients reported that poor glycemic control was associated with increased risks of all-cause mortality, cancer-specific mortality, and cancer recurrence. Dose-response analyses also showed that each 1-unit increase in HbA(1c) was associated with increased risks of mortality. These findings highlight the importance of maintaining optimal glycemic control in cancer patients with diabetes.