Urinary equol, but not daidzein and genistein, was inversely associated with the risk of type 2 diabetes in Chinese adults

  • Hong-Li Dong
  • Xin-Yi Tang
  • Yun-Yang Deng
  • Qing-Wei Zhong
  • Cheng Wang
  • Zhe-Qing ZhangEmail author
  • Yu-Ming ChenEmail author
Original Contribution



Many studies have examined the association of isoflavone intake with type 2 diabetes (T2D), and produced inconsistent results. Few studies, however, explored the association using objective biomarkers (particular for daidzein metabolite-equol) of isoflavones. We aimed to explore the association of urinary equol, daidzein and genistein concentrations with T2D and examine the mediating roles of high-sensitivity C-reactive protein (hsCRP) and retinol binding protein 4 (RBP4).


This prospective study included 2818 subjects. Urinary concentrations of equol, daidzein and genistein were measured by high-performance liquid chromatography-tandem mass spectrometry. The associations between urinary isoflavones and T2D incidence were evaluated by cox proportional hazards model.


After adjustment for covariates, urinary equol except daidzein and genistein was inversely associated with T2D incidence. In comparison with the first tertile, multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for T2D incidence in the second and third tertile of equol concentration were 0.52 (0.37, 0.73) and 0.72 (0.53, 0.97), respectively. In stratified analyses by sex, the HR (95% CI) of men in the second vs. first tertile of equol was 0.29 (0.14, 0.58). Equivalent estimation in women was 0.67 (0.45, 1.01). Neither women nor men in the third tertile showed significant difference of T2D incidence compared with the first tertile. In path analyses, there was no evidence of mediating effects of hsCRP and RBP4 on the “equol-T2D” relationship.


Urinary equol was favorably associated with a decreased T2D incidence in Chinese adults. The equol–T2D relationship might not be mediated by hsCRP and RBP4.

Trial registration

This study has been registered at as NCT03179657.


Daidzein Equol Genistein Type 2 diabetes 



Adjusted goodness of fit index


Confidence interval


Coefficient of variation


Estrogen receptors


Fasting blood glucose


Food-frequency questionnaire


The goodness of fit index


The Guangzhou Nutrition and Health Study


High-sensitivity C-reactive protein


Hazard ratio


Odd ratio


Retinol binding protein 4


Randomized controlled trial




Type 2 diabetes



We thank other participants and staff who contributed to the present study.

Author contributions

YMC designed the research. HLD, XYT, YYD, QWZ and CW conducted research. HLD analyzed the data. HLD wrote the paper. YMC and ZQZ critically revised the manuscript. YMC had primary responsibility for final content. All authors read and approved the final manuscript.


This study was jointly supported by the National Natural Science Foundation of China (Nos. 81472965 and 81502798), Natural Science Foundation of Guangdong Province, China (No. 2015A030310399), and the 5010 Program for Clinical Researches (No. 2007032) of the Sun Yat-sen University (Guangzhou, China).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public HealthSun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.The Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  3. 3.Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Nutrition and Food Hygiene, School of Public HealthSouthern Medical UniversityGuangzhouPeople’s Republic of China

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