Why the study?
Patients with concurrent HF and T2DM have a markedly elevated cancer risk, yet the optimal glycemic control target and potential nonlinear relationships between HbA1c and cancer outcomes in this population were unclear.
Does baseline HbA1c level (<5.0%, 7.0–8.9%, or ≥9.0% vs 5.0–6.9%) alter incident all-cause cancer risk in patients with concurrent heart failure and type 2 diabetes mellitus?
Does baseline HbA1c level (<5.0%, 7.0–8.9%, or ≥9.0% vs 5.0–6.9%) alter incident all-cause cancer risk in patients with concurrent heart failure and type 2 diabetes mellitus?
In patients with concurrent heart failure and type 2 diabetes mellitus, both tightly controlled (<5.0%) and elevated (≥7.0%) baseline HbA1c levels are associated with increased incident cancer risk compared to a moderate HbA1c target of 5.0–6.9%.
Background Patients with concurrent heart failure (HF) and type 2 diabetes mellitus (T2DM) have a markedly elevated cancer risk, yet the optimal glycemic control target for reducing oncologic risk in this population is unclear. Nonlinear relationships between glycemic markers and cancer outcomes have been suggested, but this remains uncharacterized in HF-T2DM patients. Purpose This study aimed to investigate the association between baseline HbA1c levels and incident cancer in patients with coexisting HF and T2DM. Methods This population-based retrospective cohort study utilized data from the Clinical Data Analysis and Reporting System (CDARS). We included adults with newly diagnosed concurrent HF and T2DM (2004–2021) and no prior cancer diagnosis. Baseline HbA1c was categorized into 4 clinically relevant strata: <5.0%, 5.0–6.9% (reference), 7.0–8.9%, and ≥9.0%. The primary endpoint was incident all-cause cancer. Cox proportional hazards models with restricted cubic splines (RCS) were used to test for nonlinearity and quantify hazard ratios (HRs). Multivariable models were adjusted for age, sex, comorbidities, and medications. Results A total of 62,845 patients were included (mean age 68.2 years; 58.4% male). Over a median follow-up of 4.8 years, 4,217 incident cancer cases were documented (incidence rate: 10.2 per 1000 person-years). Restricted cubic spline analysis confirmed a significant U-shaped association between baseline HbA1c and cancer risk (P for nonlinearity <0.001). Compared with the reference group (HbA1c 5.0–6.9%, lowest cancer incidence), the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for incident cancer were 1.28 (1.15–1.43) for HbA1c <5.0%, 1.19 (1.08–1.31) for HbA1c 7.0–8.9%, and 1.37 (1.23–1.53) for HbA1c ≥9.0%, and this U-shaped pattern remained consistent across all prespecified subgroups of age, sex, and comorbidities (P for interaction >0.05 for all analyses). Conclusion In patients with coexisting HF and T2DM, baseline HbA1c levels exhibit a robust U-shaped association with incident cancer risk. Both excessively tight (HbA1c <5.0%) and poor glycemic control (HbA1c ≥7.0%) are associated with significantly higher cancer risk, whereas a moderate HbA1c range of 5.0–6.9% correlates with the lowest oncologic risk. These findings support a personalized, moderate glycemic control strategy for cancer prevention in this high-risk cardiometabolic population.Association of HbAle with Cancer Risk
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Qi et al. (2026) studied this question.
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