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

Abstract

Abstract 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 (HbA1c) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA1c or per 1-unit HbA1c 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 HbA1c ≥ 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 HbA1c (%) 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.