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

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 (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.