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Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes

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Abstract

Purpose

Compared with people without diabetes, people with type 2 diabetes (T2D) are at higher risk of both subnormal vitamin C status and increased oxidative stress. We aimed to investigate the associations of serum vitamin C concentrations with all-cause and cause-specific mortality among adults with and without T2D.

Methods

The current analysis included 20,045 adults (2691 people with T2D and 17,354 without T2D) from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2003–2006. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were used to examine the dose–response relationship.

Results

After a median follow-up of 17.3 years, 5211 deaths were documented. Individuals with T2D had a lower level of serum vitamin C concentrations compared with those without T2D (the median value: 40.1 vs. 44.9 μmol/L). Furthermore, the dose–response relationship between serum vitamin C and mortality showed different patterns between participants with and without T2D. In individuals without T2D, there was a nonlinear association of serum vitamin C concentrations with all-cause, cancer, and CVD mortality, with the lowest risk around a serum vitamin C concentration of 48.0 μmol/L (all Poverall < 0.05, Pnonlinearity < 0.05). In contrast, among those with T2D in the similar concentration range, higher serum vitamin C levels (ranged from 0.46 to 116.26 μmol/L) were linearly associated with lower all-cause and cancer mortality (both Poverall < 0.05, Pnonlinearity > 0.05). Significant additive interaction was observed between diabetes status and serum vitamin C levels with regard to all-cause and cancer mortality (P < 0.001). In addition, C-reactive protein, gamma-glutamyl transpeptidase, and HbA1c explained 14.08, 8.96, and 5.60% of the association between serum vitamin C and all-cause mortality among individuals with T2D, respectively.

Conclusions

Higher serum vitamin C concentrations were significantly associated with lower risk of mortality in participants with T2D in a linear dose–response manner, while a nonlinear association was observed in participants without T2D, with an apparent threshold around 48.0 μmol/L. These findings suggest that the optimal vitamin C requirement may differ in individuals with and without T2D.

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Data availability

Some or all data generated or analyzed during this study are included in this published article or in the data repositories listed in References.

Code availability

Data described in the manuscript, code book, and analytic code will be made available upon request pending application and approval from the corresponding author.

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Funding

Gang Liu was funded by Grants from National Nature Science Foundation of China (82073554 and 82273623), the Hubei Province Science Fund for Distinguished Young Scholars (2021CFA048), and the Fundamental Research Funds for the Central Universities (2021GCRC076). An Pan was supported by Grants from National Nature Science Foundation of China (81930124 and 82021005), and the Fundamental Research Funds for the Central Universities (2021GCRC075). The funders had no role in the study design, data acquisition, analysis, or interpretation of results.

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Author notes

  1. Yunjing Ou and Zixin Qiu: Co-first authors.

Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety (Huazhong University of Science and Technology), Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Yunjing Ou, Zixin Qiu, Tingting Geng, Qi Lu, Rui Li, Lin Li, Kai Zhu, Xue Chen, Xiaoyu Lin, Sen Liu & Gang Liu

  2. Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    An Pan

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Contributions

GL designed the study. ZQ performed statistical analysis. YO drafted the manuscript and checked the accuracy of statistical analysis. All of the authors participated in the interpretation of the results and critical revision of the manuscript.

Corresponding author

Correspondence to Gang Liu.

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Ou, Y., Qiu, Z., Geng, T. et al. Associations of serum vitamin C concentrations with risk of all-cause and cause-specific mortality among individuals with and without type 2 diabetes. Eur J Nutr 62, 2555–2565 (2023). https://doi.org/10.1007/s00394-023-03173-1

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