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Epidemiology

Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case–control study

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Abstract

Background

To evaluate the associations between pre-diagnostic levels of serum insulin, glucose and insulin resistance (HOMA-IR) and future risk of incident primary liver cancer (PLC) or chronic liver disease (CLD)-related mortality.

Methods

We used a nested case-control design to evaluate subjects over 22 years of follow-up. Glucose, insulin, and three markers of hepatitis B virus (HBV) and hepatitis C virus were measured in fasting baseline serum from 119 incident PLCs, 157 CLD-death cases and 512 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to estimate the associations between insulin, glucose, HOMA-IR and the risk of PLC or CLD death.

Results

Compared with the lowest quartile of insulin, multivariable adjusted models showed that subjects in the highest quartile had elevated odds of develo** PLC (ORQ4/Q1 = 2.42, 95% CI = 1.26–4.75, Ptrend = 0.007), particularly in HBV-positive subjects (Pinteraction = 0.040), and of CLD death (ORQ4/Q1 = 1.80, 95% CI = 1.02–3.21, Ptrend = 0.018). For glucose, in the HBV-positive group, subjects in the fourth quartile had an increased risk of PLC (ORQ4/Q1 = 2.18, 95% CI = 1.07–4.60, Ptrend = 0.009), and of CLD mortality (ORQ4/Q1 = 1.75, 95% CI = 0.95–3.28, Ptrend = 0.019). Subjects with the highest HOMA-IR values had a threefold risk of develo** PLC (ORQ4/Q1 = 2.94, 95% CI = 1.54–5.87, Ptrend = 0.001), and a twofold risk of CLD death (ORQ4/Q1 = 2.20, 95% CI = 1.25–3.94, Ptrend = 0.005).

Conclusions

We found that serum insulin and HOMA-IR could potentially be risk factors for PLC or CLD death.

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Data availability

The data generated in this study are available upon request from the corresponding author.

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Funding

This work was supported in part by National Cancer Institute contracts (N01-SC-91030, N01-RC-47701 and N02CP-2017-00047 to YL Qiao) to the National cancer center, Chinese Academy of Medical Sciences, and in part by the National Cancer Center, Chinese Academy of Medical Sciences.

Author information

Authors and Affiliations

  1. School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Bei**g, China

    Jian Yin, Jianfeng Cui & Youlin Qiao

  2. Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Bei**g, China

    Jian Yin, Yiwei Liu, Huan Yang, Bin Liu, **hu Fan, Wen Chen & Youlin Qiao

  3. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, 20850, USA

    Neal D. Freedman, Sanford M. Dawsey, Philip R. Taylor & Christian C. Abnet

  4. Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China

    Liangyu Yin

  5. Department of Clinical Nutrition, Da** Hospital, Third Military Medical University (Army Medical University), 400042, Chongqing, China

    Liangyu Yin

Authors
  1. Jian Yin
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  2. Neal D. Freedman
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  3. Yiwei Liu
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  4. Sanford M. Dawsey
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  5. Huan Yang
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  8. Bin Liu
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  9. Jianfeng Cui
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  11. Wen Chen
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Contributions

Study concepts and study design: JY, WC and Y-LQ; data acquisition: JY, L-YY, Y-WL, HY, J-HF, J-FC, BL, NDF and SMD; quality control data and algorithms: J-HF and WC; data analysis, interpretation and statistical analysis: JY; manuscript preparation: JY; manuscript editing: YJ and WC; manuscript review: WC, SMD, NDF, CCA, PRT and Y-LQ; all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wen Chen or Youlin Qiao.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The study was performed according to the guidelines of the Helsinki declaration. All consent procedures, including human specimen collection, were approved by the Institutional Review Boards of the U.S. National Institutes of Health and the Chinese Academy of Medical Sciences (Bei**g, China), and all participants provided written informed consent.

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Yin, J., Freedman, N.D., Liu, Y. et al. Associations between serum glucose, insulin, insulin resistance and the risk of incident primary liver cancer or chronic liver disease mortality: a nested case–control study. Br J Cancer 128, 275–284 (2023). https://doi.org/10.1038/s41416-022-02042-8

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