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Development of malignancies and changes in time-dependent hemoglobin A1c among a nondiabetic population: longitudinal analysis

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A Letter to the Editor to this article was published on 31 October 2019

Abstract

Background

The fluctuation of hemoglobin A1c (HbA1c) and changes in health habits over time was not considered in previous studies. The aim of this study was to evaluate the time-sequenced association between malignancy incidence and HbA1c with a longitudinal study design using repeated measurements of HbA1c.

Methods

A retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. All participants who underwent voluntary health check-ups at the hospital were included. Our outcomes were the development of malignancy. We compared these outcomes using HbA1c categories. Longitudinal analyses were conducted with a mixed effects model in which time-dependent HbA1c measurements were applied to consider fluctuations in HbA1c levels, adjusted for covariates.

Results

A total of 77,385 nondiabetic participants were included in the study; the mean age was 44.7 and 49.4% of participants were male. During a median follow-up of 1588 (interquartile range 730–2946) days, 4506 (5.8%) participants developed malignancies. The relationship between future malignancies and HbA1c was U-shaped; both the lower HbA1c groups (OR 1.31, 95% CI 1.17–1.46 for < 5.0%) and the higher HbA1c group (OR 1.87, 95% CI 1.03–3.39 for ≥ 7.5%) had significantly higher odds ratios compared to the 5.5–5.9%. The lowest HbA1c was associated with higher odds of breast cancer (OR 1.5, 95% CI 1.21–1.86) and female genital cancer (OR 1.57, 95% CI 1.04–2.37).

Conclusions

Our study found a U-shaped association between HbA1c and future malignancies among nondiabetic people but did not find additional risk at the prediabetic level. Low HbA1c may be associated with the incidence of breast cancer and female genital cancer.

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Funding

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Authors and Affiliations

  1. Division of General Internal Medicine, Department of Medicine, St. Luke’s International Hospital, Tokyo, Japan

    Daiki Kobayashi & Osamu Takahashi

  2. Department of Epidemiology, St. Luke’s International University Graduate School of Public Health, Tokyo, Japan

    Daiki Kobayashi & Osamu Takahashi

  3. Fujita Health University, Toyoake, Japan

    Daiki Kobayashi

  4. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Nagato Kuriyama

  5. Department of Endocrinology, St. Luke’s International Hospital, Tokyo, Japan

    Hiroshi Noto & Azusa Aida

  6. Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Azusa Aida

  7. Ohta Nishinouchi Hospital, Koriyama, Japan

    Takuro Shimbo

Authors
  1. Daiki Kobayashi
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  2. Nagato Kuriyama
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  3. Hiroshi Noto
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  4. Azusa Aida
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  5. Osamu Takahashi
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  6. Takuro Shimbo
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Corresponding author

Correspondence to Daiki Kobayashi.

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Conflicts of interest

All authors had no conflict of interest.

Ethical approval

The St Luke’s International Hospital Ethics Committee Institutional Review Board approved this study (17-R022: comprehensive approval for studies which focusing on HbA1c, including this study).

Informed consent

Obtaining informed consent was waived by the ethics committee, because this study was a retrospective study. However, participants were noticed this study by viewing this study information on the website of the hospital. Those who declared not to participate in this study were excluded.

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Kobayashi, D., Kuriyama, N., Noto, H. et al. Development of malignancies and changes in time-dependent hemoglobin A1c among a nondiabetic population: longitudinal analysis. Acta Diabetol 57, 189–196 (2020). https://doi.org/10.1007/s00592-019-01396-5

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  • DOI: https://doi.org/10.1007/s00592-019-01396-5

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