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

Suping Ling; Michael Sweeting; Francesco Zaccardi; David Adlam; Umesh T Kadam

doi:10.1186/s12885-022-10144-y

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

BMC Cancer. 2022 Oct 6;22(1):1048. doi: 10.1186/s12885-022-10144-y.

Authors

Suping Ling^{1

2}, Michael Sweeting³, Francesco Zaccardi^{4

5}, David Adlam⁶, Umesh T Kadam^{3

5}

Affiliations

¹ Department of Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK. sl617@leicester.ac.uk.
² Present address: Department of Non-communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK. sl617@leicester.ac.uk.
³ Department of Health Sciences, University of Leicester, University Road, Leicester, LE1 7RH, UK.
⁴ Leicester Real World Evidence Unit, Leicester Diabetes Centre, University of Leicester, Leicester, UK.
⁵ Leicester Diabetes Centre, University of Leicester, Leicester, UK.
⁶ Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.

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.

Keywords: Diabetes; Dose-response meta-analysis; Glycaemic control; HbA1c; Mortality; Systematic review; cancer prognosis; cancer survival.

Publication types

Meta-Analysis

MeSH terms

Diabetes Mellitus, Type 1*
Diabetes Mellitus, Type 2* / complications
Glycated Hemoglobin
Humans
Neoplasms* / epidemiology
Prognosis

Substances

Glycated Hemoglobin A

Abstract

Publication types

MeSH terms

Substances

Grants and funding