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. 2025 May 26;17(1):172.
doi: 10.1186/s13098-025-01719-3.

The non-linear association between remnant cholesterol/high-density lipoprotein cholesterol ratio and diabetic retinopathy: a cross-sectional study in type 2 diabetic patients

Cuimei Wei #  1   2 , Yaohui Huang #  1   2 , Ping Xi  1   2 , Zhilan Shen  1   2 , Wenjing Liu  1   2 , Tong Li  3   4 , Gang Chen  5 , Xiaohua Xiao  6   7 , Haofei Hu  8   9
Affiliations

The non-linear association between remnant cholesterol/high-density lipoprotein cholesterol ratio and diabetic retinopathy: a cross-sectional study in type 2 diabetic patients

Cuimei Wei et al. Diabetol Metab Syndr. .

Abstract

Objective: The strong correlation between the ratio of residual cholesterol to high-density lipoprotein cholesterol (RC/HDL-c) and major cardiovascular events has been extensively studied. However, the role of this ratio in diabetic retinopathy (DR) has not been investigated. Hence, this present study aims to examine the association between the RC/HDL-c ratio and DR in patients diagnosed with type 2 diabetes mellitus (T2DM).

Methods: This study conducted a cross-sectional analysis involving a total of 1942 patients diagnosed with T2DM in two Taiwanese hospitals, spanning from April 2002 to November 2004. The primary objective was to explore the independent association between the RC/HDL-c ratio and the presence of DR, as well as proliferative diabetic retinopathy (PDR), using a binary logistic regression model. To accurately determine the shape of the association between these variables, we utilized a generalized additive model (GAM) and employed smooth curve fitting techniques. The data was downloaded from the website: https://journals.plos.org/plosone .

Results: Our study comprised participants with an average age of 64.06 ± 11.32 years, with males accounting for 43.05% of the total. Among the patients, 35.12% were found to have DR, while PDR was present in 18.23% of cases. The average RC/HDL-c ratio was calculated as 0.67 ± 0.39. Utilizing a fully adjusted logistic regression model, we investigated the potential association between the TC/HDL-c ratio and both DR and PDR. However, no statistically significant association was observed (DR: OR 1.060; 95% CI 0.707, 1.588; PDR: OR 1.258; 95% CI 0.773, 2.047). Interestingly, we did discover a non-linear association between the RC/HDL-c ratio and DR. Employing a two-piece logistic regression model and a recursive algorithm, we identified an inflection point at 0.460. When the RC/HDL-c ratio fell below 0.460, each 1-unit increase in the ratio was associated with an 11.8-fold increase in the adjusted odds of developing DR (OR = 12.824; 95% CI 3.583, 45.897). Moreover, a non-linear association between the RC/HDL-c ratio and PDR was observed, with an inflection point occurring at 0.90. When the RC/HDL-c ratio was below 0.90, a one-unit increase in the ratio was linked to a 1.46-fold increase in the adjusted odds of PDR (OR = 2.459; 95% CI: 1.245, 4.857).

Conclusion: This study contributes valuable insights into the intricate association between the RC/HDL-c ratio and both DR and PDR in individuals diagnosed with T2DM. By identifying a non-linear association, our findings enhance the existing knowledge surrounding the link between the RC/HDL-c ratio and the development of DR and PDR.

Keywords: Diabetic retinopathy; Generalized additive model; Non-linear; Proliferative diabetic retinopathy; Remnant cholesterol/high-density lipoprotein cholesterol ratio.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: In their previous publication, Chen et al. clearly stated that this study was conducted with the approval of the institutional review board at Kaohsiung Medical University Hospital (Approval No. KMUHIRB-E-20150029) and in accordance with the ethical principles outlined in the Declaration of Helsinki. Prior to participating, all patients willingly provided their informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of study participants
Fig. 2
Fig. 2
Prevalence of DR and PDR according to the quartiles of RC/HDL-c ratio. A With the increase of RC/HDL-c ratio, the trend of DR prevalence was not statistically significant (P = 0.074 for trend). B As the RC/HDL-c ratio level increased, the prevalence of PDR also showed a trend of increasing (P = 0.031 for trend)
Fig. 3
Fig. 3
DR and PDR prevalence rate of age stratification by 20 intervals. A Demonstrated that male respondents had a higher prevalence of DR than female subjects regardless of age group. The prevalence of DR rose with age in both male and female individuals (except for those beyond the age of 80). B Demonstrated that male subjects had a higher prevalence of PDR than female subjects, regardless of age group. PDR prevalence rose with age in both male (except for age < 40) and female (except for age > 80) subjects
Fig. 4
Fig. 4
The non-linear association between RC/HDL-c ratio and the risk of DR. In order to evaluate the association between the ratio of RC/HDL-c and the risk of DR, we utilized a generalized additive model and performed smooth curve fitting. The solid red line represents the smooth curve fit between variables. Blue bands represent the 95% of confidence interval from the fit. The results unveiled a nonlinear correlation between the RC/HDL-c ratio and DR
Fig. 5
Fig. 5
The non-linear association between RC/HDL-c ratio and the risk of PDR. To assess the link between the RC/HDL-c ratio and the risk of PDR, we employed a generalized additive model and smooth curve fitting. The solid red line represents the smooth curve fit between variables. Blue bands represent the 95% of confidence interval from the fit. The findings revealed a non-linear association between the RC/HDL-c ratio and PDR
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