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Circulating level of homocysteine contributes to diabetic retinopathy associated with dysregulated lipid profile and impaired kidney function in patients with type 2 diabetes mellitus

Abstract

Background

To test the hypothesis that elevated plasma levels of homocysteine (Hcy) and lipoprotein (a) (LPA) contribute to diabetic retinopathy (DR) associated with dysregulated lipid profile, dyslipidaemia, and kidney function.

Methods

A total of 83 patients with type 2 diabetes mellitus (T2DM) were enrolled in this prospective case-control study. Patients were categorized into those with no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR). Age and sex-matched individuals with no diabetes were included in the control group. Biochemical tests, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Hcy, LPA, lipid profile, and urine microalbumin (UMA), were evaluated.

Results

Hcy was negatively correlated with high-density lipoprotein-cholesterol (HDL-C) (p < 0.05), but positively correlated with [total cholesterol (TC)-HDL-C)/HDL-C] (p < 0.05), low-density lipoprotein cholesterol (LDL-C)/HDL-C (p < 0.05), and UMA (p < 0.05). Traditional risk factors, Hcy, arteriosclerosis-associated plasma indices, and UMA, resulted as the independent risk factors for the occurrence of DM and DR. After controlling for age, sex, duration of DM, and FBG, a multiple ordinal logistic regression model showed that LPA [OR = 2.90, 95% confidence interval (95% CI) 1.16–7.23, p = 0.023)], LDL-C (OR = 4.28, 95% CI 1.24–14.79, p = 0.021), and (TC-HDL-C)/HDL-C (OR = 1.92, 95% CI 1.05–3.53, p = 0.035) were risk factors for DM and DR.

Conclusions

Hcy and LPA contributed to DM and DR. Hcy was positively correlated with kidney dysfunction and the ratios of lipid profiles, and negatively with HDL-C, LPA, LDL-C, and (TC-HDL-C)/HDL-C resulted as predictors of the occurrence of DM and severity of DR.

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Fig. 1: Correlations of Hcy and LPA with lipid profiles and UMA in Control, DM, NPDR, and PDR groups.
Fig. 2: The multivariable ordinal logistic regression model showed LPA and LDL-C were strong risk factors for the occurrence of DM and DR.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Funding

This work was supported by the National Natural Science Foundation of China [Grant 81570850 and 82070988] and the Ministry of Science and Technology Foundation of China [Grant 2016YFC1305604].

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Authors

Contributions

XZ contributed to conception and design of the study, drafted and revised the manuscript and perform statistical analysis. XC and YN organized the database, performed the experiments and statistical analysis and drafted the manuscript. ZG, AF and XC performed the statistical analysis. QW, BQ, RX and YW helped to enroll patients. All authors contributed to manuscript revision, read, and approved the submitted version.

Corresponding author

Correspondence to Xinyuan Zhang.

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The authors declare no competing interests.

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Chen, X., Zhang, X., Nie, Y. et al. Circulating level of homocysteine contributes to diabetic retinopathy associated with dysregulated lipid profile and impaired kidney function in patients with type 2 diabetes mellitus. Eye 37, 1383–1389 (2023). https://doi.org/10.1038/s41433-022-02144-w

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