Lung Cancer Risk Rises With A1c, Falls With Medication

Miriam E. Tucker, for Medscape

January 23, 2023

Researchers published the study covered in this summary on Preprints with The Lancet as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Results from a large database study has shown a positive association between prediabetes, diabetes, and incident lung cancer.

  • Treatment with glucose-lowering medications was significantly linked with a reduced rate of incident lung cancer.

  • The relationship between incident lung cancer and A1c was nonlinear with the strongest associations occurring at A1c levels of 32-42 mmol/mol (5.1%-6.0%), levels that fall short of the cutoff for a diagnosis of diabetes, and at the lower end, fall short of the definition of prediabetes.

  • The risk of lung cancer was also more pronounced among participants less than 60 years old, current smokers, and those with a high genetic risk for lung cancer.

Why This Matters

  • Lung cancer is the leading cause of cancer-related mortality worldwide.

  • Until this study, little has been known about the risk for incident lung cancer across the glycemic spectrum. Previous population-based studies investigating the link between diabetes and prediabetes and lung cancer have had mixed results.

  • The findings are new evidence that prediabetes and diabetes increase the risk of incident lung cancer and that use of antidiabetic medications may reduce the risk.

  • Future research into biologic mechanisms is needed to explain the association between blood glucose and lung cancer and to inform clinical practice and health policy.

Study Design

  • The study used data from a total of 283,257 cancer-free adults recruited between 2006 and 2010 in the UK Biobank.

  • Researchers subdivided the study cohort based on 2009 criteria for diabetes and prediabetes. They classified those with an A1c of less than 42 mmol/mol (less than 6.0%) as having normoglycemia; about 91% of the cohort. They classified those with an A1c of 42-47 mmol/mol (6.0%-6.4%) as having prediabetes; about 3% of the cohort. And they classified those with an A1c of at least 48 mmol/mol (at least 6.5%), or self-reported a diagnosis of diabetes, or were taking antidiabetic medications, as having diabetes; about 6% of the cohort.

Key Results

  • Among the 283,257 participants, 2355 (0.83%) developed lung cancer during a median follow-up of about 11 years.

  • Elevated A1c, prediabetes, and diabetes were each significantly associated with an increased incidence of lung cancer.

  • After adjustment for all potential confounders, each standard deviation (6.67 mmol/mol) increase in A1c was associated with a significant 3% increase in the risk of incident lung cancer.

  • Those with prediabetes had a significant 37% increased rate of lung cancer compared with people with normoglycemia after full adjustment, and people with diabetes had a significant 20% relative increase.

  • Participants with diabetes who were taking glucose-lowering medication did not have a significantly increased risk of incident lung cancer, but people with diabetes and not taking any medication had a significant 33% increased incidence of lung cancer.

  • In an analysis that considered A1c as a continuous variable, and after adjustment for all potential confounders, the incident lung cancer risk decreased with increasing levels of A1c until about 32 mmol/mol (5.1%), then increased sharply until around 42 mmol/mol (6.0%), and then increased at a more gradual rate as A1c levels further increased.

  • The dose–response association between A1c and incident lung cancer was stable when stratified by age, sex, ethnicity, smoking status, and genetic risk.


  • Only baseline data on glycemic status were used.

  • A large number of participants were excluded because of missing data.

  • The findings may have been affected by unknown confounders.

  • Generalizability of the findings is uncertain beyond the predominantly White study population.


  • The study received no commercial funding.

  • None of the authors had disclosures.

This is a summary of a preprint research study, "Associations of glycosylated hemoglobin, pre-diabetes, and diabetes with incident lung cancer: A large prospective cohort study," by researchers at several different centers in China and the United States on Preprints with The Lancet and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found here.


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