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High levels of serum uric acid are associated with microvascular complications in patients with long-term diabetes

Diabetology & Metabolic Syndrome volume 17, Article number: 106 (2025) Cite this article

Abstract

Aims

To assess the association between serum uric acid (SUA) level and the prevalence of diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with long-term diabetes.

Methods

A cross-sectional analysis was conducted involving diabetic patients from Shanghai General hospital during October 2018 and October 2021. Participants underwent measurements of SUA, renal function test and DR assessments via fundus photography. Multivariable ordinal logistic regression models assessed odd ratios (ORs) and 95% confidence intervals (95% CIs) for the progression of DR and CKD. Receiver operating characteristics (ROC) curves identified SUA thresholds, categorizing participants into low and high SUA groups.

Results

Among the 1015 patients with diabetes, SUA levels were higher in individuals with advanced CKD stages (p < 0.001, compared with stage 1 CKD) and vision-threatening diabetic retinopathy (VTDR) (p = 0.019, compared with no diabetic retinopathy (NDR)). In multivariable models adjusted for potential confounders, higher SUA levels were associated with an increased risk of DR (OR: 1.002, 95% CI: 1.001–1.004) and CKD (OR: 1.008, 95% CI: 1.006–1.011). Notably, SUA levels exceeding 354.0 µmol/L (95% CI: 318.9–393.2) and 361.0 µmol/L (339.2–386.3) were associated with 1.571-fold (95% CI: 1.139–2.099, P = 0.006 for DR) and 1.395-fold (95% CI: 1.033–1.885, P = 0.030 for CKD) increased risks, respectively. Gender-specific analyses also demonstrated a positive correlation between higher SUA levels and the incidence of DR and CKD in both males and females.

Conclusions

Elevated SUA levels are independently coincided with increased risks of DR and CKD, suggesting that SUA may serve as a potential risk marker for diabetic complications.

Introduction

Diabetes mellitus (DM), a chronic metabolic disorder characterized by elevated blood glucose levels, has seen a notable increase in prevalence, making it a considerable public health concern. Recent data from the World Health Organization (WHO) suggest that an estimated 462 million individuals globally are living with type 2 diabetes [1]. Both type 1 and type 2 diabetes are associated with cardiovascular, renal, ocular and neurological complications [2].

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are common complications in patients with diabetes and the most frequent causes of blindness and death [3]. Both of them are microvascular injuries caused by hyperglycemia, thus share some common metabolic alterations that contribute to the pathogenesis of diabetic complications. Several research suggested the development and progression of DN and retinopathy are influenced not just by hyperglycemia but also by factors including age, smoking, obesity, hypertension, dyslipidemia, and inflammation [4]. Therefore, identifying additional contributors to the pathophysiological mechanisms underlying diabetic complications is crucial.

Uric acid (UA) is the degradation product of purines, and hyperuricemia is highly prevalent in patients with diabetes [5], due to impaired renal function resulting in decreased renal excretion of UA [6]. Serum uric acid (SUA) has been recently recognized as a risk factor for both macrovascular and microvascular diseases. On the one hand, previous studies [7, 8] have suggested a potential link between elevated UA levels and the development and progression of diabetes. On the other hand, high levels of UA can also contribute to inflammation, oxidative stress, and apoptosis [9], potentially playing a significant role in the development of diabetic complications. Several clinical studies have shown an association between elevated UA levels and DN [10, 11]. However, clinical trials have yielded inconsistent findings regarding the link between UA and diabetic retinopathy (DR) [12,13,14]. Our previous clinical study [15], a metabolomics-based investigation, showed a significant increase of uric acid levels in vitreous samples from patients with proliferative diabetic retinopathy (PDR) compared to non-diabetic controls (UA intensity, 694.2 vs. 475.8, p < 0.01). This result suggests a potential involvement of UA in the development of DR. The elevated levels of UA in the vitreous may be due to both local metabolic changes within the retina and a potential increase in systemic UA levels. Although alterations in vitreous uric acid levels exhibit more relevant to disease mechanisms, the assessment of SUA remains more suitable for disease prevention and management.

Therefore, we conducted a cross-sectional study in patients with diabetes for at least 5 years to better understand the relationship between SUA and the occurrence of diabetic microvascular complications.

Method

Patients

The cross-sectional study recruited patients with diabetes (including both Type 1 and Type 2 diabetes mellitus), who were from the Department of Endocrinology at Shanghai General Hospital, China between October 2018 and October 2021. Diabetes was determined through the assessment of plasma glucose levels, specifically with criteria such as fasting blood glucose (FBG) ≥ 7.0 mmol/L or 2-hour plasma glucose (2 h PG) exceeding 11.1 mmol/L during a 75 g oral glucose tolerance test [16]. Patients were included if diagnosed with diabetes for > 5 years, with available SUA data and fundus photography. We excluded patients with gestational diabetes or diabetes induced by medication use or other endocrine diseases. Finally, a total of 1015 subjects were included in this study. This study was approved by the Institutional Review Board of Shanghai General Hospital (IRB No.2017KY209-5C24-1) and strictly adhered to the ethical principles of medical research involving human subjects established by the Declaration of Helsinki (1964) and its subsequent amendments. Written informed consent was obtained from each participant before the study began. All participants were fully informed of the objectives of the research and consented to the use of their data for academic purposes, including publication.

Diagnose of diabetic retinopathy (DR)

For each eye of each subject, one standard color fundus image was obtained with 45° field of view, non-stereoscopic and macula-centered. A modified grading scale reported previously was used for the classification of DR and diabetic macular edema (DME) [17]. Patients are grouped according to the degree of the eye with the worse grade when the grades of both eyes were inconsistent. Then the patients were grouped into non-DR (NDR), non-vision threatened diabetic retinopathy (non-VTDR) which including mild and moderate non proliferative diabetic retinopathy (NPDR), and VTDR which including severe NPDR, PDR and DME. All fundus images were assessed by the Ophthalmology Center of the Shanghai General Hospital (National Clinical Research Center for Eye Diseases).

Demographic data and laboratory measurements

In the survey, patients were subjected to a standard inquiry regarding their medical history, physical examination, and laboratory tests. Various demographic information including age, sex, height, weight, blood pressure, smoking or alcohol consumption habits were recorded. Additionally, their medical history encompassing both microvascular and macrovascular complications along with treatment approaches including medications for hypertension and diabetes were documented.

In this study, blood samples were obtained from the patients’ antecubital vein at overnight fasting for biochemical measurement using a conventional fully automated biochemical analyzer, including lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)), blood urea nitrogen (BUN), serum creatinine, SUA, fasting blood glucose and postprandial blood glucose. SUA values are reported in µmol/L (1 mg/dL = 59.48 µmol/L). Urine samples were collected to test the levels of urinary albumin–creatinine ratio (UACR). The estimated glomerular filtration rate (eGFR) is used to estimate kidney function and determine chronic kidney disease (CKD) staging, using the following formula: eGFR [mL/ (min × 1.73 m2)] = 194 × Cr− 1.094 × age− 0.287 (×0.739 for female patients) [18].

Statistical analysis

Multiple imputation was conducted in this study to impute missing values using the MI procedure in SPSS software (version 26.0.0.2; SPSS, Chicago, IL, USA) under the assumption of missing at random. Five imputed datasets were generated, and pooled results were reported. The proportion of missing values for all imputed variables was less than 10%. SUA levels were measured once at baseline, with values ≥ 420 µmol/L in men and ≥ 360 µmol/L in women classified as high SUA levels. All continuous variables were non-normally distributed and expressed as median plus interquartile range (IQR). Differences between groups were evaluated using nonparametric tests. Categorical variables were presented as numbers (proportions) and comparisons between groups were made using the chi-square test. Correlations between SUA levels and other measures were evaluated by Pearson’s correlation analysis and linear regression analysis. To identify independent risk factors associated with the prevalence of DR and CKD, orderly logistic regression analyses were performed. Variables known or thought to be associated with DR or CKD were selected as covariates in statistical models. Results were presented as odds ratios (ORs) and 95% confidence intervals (95% CIs), considering P values less than 0.05 as statistically significant. Receiver operating characteristics (ROC) curves and SUA cutoff points were derived to obtain SUA groupings (low SUA group and high SUA group). Statistical analyses were performed using SPSS software and GraphPad Prism (version 9.5.0; GraphPad Software Inc., San Diego, CA, USA). The 95% CIs of SUA cutoff points were computed in Python (version 3.12).

Results

Baseline characteristics

Baseline characteristics of the study participants are depicted in Table 1. A total of 1015 participants were included, comprising 721 patients with NDR (71.03%), 241 with non-VTDR (23.7%), and 53 diagnosed with VTDR (5.2%). The mean baseline SUA was 315.1, 322.5 and 356.0 µmol/L, respectively. Comparing individuals without DR, those with VTDR exhibited higher baseline SUA levels (315.1 µmol/L vs. 356.0 µmol/L; P = 0.019) (Fig. 1). Observations also indicate an increased high uric acid exposure among individuals at DR (14% vs. 19%, P < 0.05). The duration of diabetes (P = 0.002), sex distribution (P = 0.049) and the level of HbA1c (P < 0.001) differ between the groups. The indicators that also present inter-group differences include glycated albumin, BUN, HDL- C and ALB. There was no statistically significant difference in BMI between the two groups (P = 0.306).

Table 1 Characteristics of the population grouped by diabetic retinopathy
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Fig. 1
figure 1

Serum concentrations of uric acid in groups with different stage of DR (A) and CKD (B). The average serum uric acid (SUA) level increased as the severity of DR and CKD increased. DR: Diabetic Retinopathy; NDR: Non-Diabetic Retinopathy; VTDR: Vision-Threatening Diabetic Retinopathy; CKD: Chronic Kidney Disease; CKD1: Stage 1 CKD; CKD2: Stage 2 CKD; CKD3: Stage 3 CKD; ns: Non-Significant; *: p < 0.05; ***p < 0.001; ****:P < 0.0001

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Subsequently, we categorized all patients into three groups based on CKD staging (Table S1). Compared to the CKD 1 group, patients with CKD 2&3 exhibited significantly higher SUA levels (314.2 ± 134.3 µmol/L vs. 362.9 ± 144.5 µmol/L, p < 0.001; 314.2 ± 134.3µmol/L vs. 359.1 ± 173.2 µmol/L, p < 0.001, respectively). An analysis of high SUA level exposure within each group revealed a higher proportion among individuals in advanced CKD stages (12.6% vs. 30.0% vs. 30.3%, p < 0.001). Several parameters exhibit significant differences between patients at different stages of CKD, including age, the duration of diabetes, DBP, ALB, BUN, Scr, eGFR, 0 h-PG and the prevalence of hypertension.

SUA levels are independent risk factors for both DR and CKD

Upon examination of SUA as a continuous variable, an orderly logistic regression analysis revealed that SUA was an independent risk factor for the progression of both DR and CKD (Fig. 2). After adjusting for sex, age, diabetic duration, smoking history, HDL-C, ALB, and HbA1c, the risk factors for DR progression were high SUA (OR: 1.002, 95% CI: 1.001–1.004, p = 0.017), longer duration of DM (OR, 1.005; 95% CI = 1.125–1.310; p < 0.001), young age (OR, 0.959; 95% CI = 0.945–0.972; p < 0.001), low ALB (OR, 0.951; 95% CI = 0.921–0.981; p = 0.02), and high HbA1c (OR, 1.214; 95% CI = 1.125–1.310; p < 0.001). The study found that independent risk factors for CKD, after multivariate adjustments, included high SUA levels (OR: 1.008, 95% CI: 1.006–1.011), low Hb (OR, 0.977; 95% CI = 0.965–0.989; p < 0.001), and older age (OR, 1.155; 95% CI = 1.121–1.188; p < 0.001).

Fig. 2
figure 2

Forest plot demonstrating odds ratios and 95% CIs for associations between SUA and DR prevalence (A) and prevalence of CKD (B) SUA: Serum Uric Acid; BMI: Body Mass Index; HDL-C: High-Density Lipoprotein Cholesterol; ALB: Albumin; HbA1c: Hemoglobin A1c; Hb: Hemoglobin, DR: Diabetic Retinopathy; CKD: Chronic Kidney Disease

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ROC curves and ideal SUA cutoff for prediction of DR and CKD

In order to determine clinically meaningful SUA thresholds for predicting the occurrence of DR and CKD, we utilized ROC curves to obtain cutoffs to optimize both sensitivity and specificity (Table 2). To discriminate DR or CKD from patients with diabetes, the average cutoff values for SUA in general population were 354.0 µmol/L (95% CI: 318.9-393.2) and 361.0 µmol/L (95% CI: 339.2-386.3), respectively.

Table 2 Results of receiver operating characteristic curve identifying the threshold of serum uric acid for DR and CKD
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In the analysis of DR, 650 patients exhibited SUA levels below 354.0 µmol/L (low SUA group), while 365 had a SUA level equal to or above 354.1 µmol/L (high SUA group). Table 3 summarizes the clinical characteristics of these two groups. The average age of the high SUA group was lower compared to that of the low SUA group (p = 0.002). Patients in the high SUA group displayed higher systolic blood pressure (SBP), diastolic blood pressure (DBP), and a greater percentage in the history of hypertension, smoking and alcohol consumption compared to those in the low SUA group. There were no significant differences between the two groups regarding diabetes duration and percentages of patients with NDR, non-VTDR, CKD1, and CKD3. In terms of laboratory parameters, BUN, Scr, TG levels were elevated in the high SUA group compared to the low SUA group (p < = 0.001 for all three parameters). However, there were no significant differences observed in TC and LDL-c levels between the two groups.

Table 3 Characteristics of the entire population grouped according to the identified thresholds for a risk of DR
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Considering the sex of the patients, the clinical characteristics of individuals with high and low SUA levels were analyzed based on sex-specific cutoffs. The results are presented in table S2 for males and table S3 for females. The thresholds for SUA for DR worsening were 355.1 µmol/L in men and 352.1 µmol/L in women. The thresholds for SUA for CKD worsening were 361.0 µmol/L in men and 353.6 µmol/L in women. Table 2 provides a summary of the sex-specific ideal cutoffs for DR and CKD as well as the ranges of sensitivity and specificity.

High SUA are independent risk factors for the progression of DR and CKD

In the analysis of univariate orderly logistic regression, there was a correlation between elevated SUA levels and an increased risk of DR progression in the overall population (OR, 1.512; 95% CI = 1.148–1.991; p < 0.003). However, this association was not observed in either male (OR, 1.354; 95% CI = 0.960–1.910; p = 0.084) or female (OR, 1.607; 95% CI = 0.980–2.635; p = 0.060) subpopulations according to the crude model results (Table 4). After adjusting for multiple variables, high SUA levels remained a significant risk factor for DR progression. In male patients, we noted a significant association between elevated SUA levels and an increased likelihood of developing DR in two different models. The ORs for the development of DR in individuals with high SUA levels compared to those with low SUA levels were 1.317 (95% CI, 0.932–1.862; P = 0.119) after adjusting for age, 1.523 (95% CI, 1.058–2.191; P = 0.024) in multivariable-adjusted model 3, and 1.498 (95% CI, 1.017–2.206; P = 0 0.041) after adjusting for age, diabetes duration, HbA1c, ALB, BUN, Cr, smoking status and eGFR. In female patients, the association between elevated SUA levels and DR was found to be significant only when adjusting for age, diabetes duration, HbA1c, and glycated albumin. The results regarding ORs for developing CKD remained consistent across male and female groups. High SUA levels were identified as an independent risk factor in all four models analyzed (Table 5).

Table 4 Orderly logistic regression analyses of the association between different levels of SUA and the prevalence of DR progression
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Table 5 Orderly logistic regression analyses of the association between different levels of SUA and the prevalence of CKD progression
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Discussion

In this cross-sectional study, we observed a positive correlation between SUA levels and the severity of DR and CKD. Elevated SUA levels were found to be linked with a higher prevalence of both DR and CKD in diabetic patient independently of other well-known and potential risk factors. SUA levels exhibited a dose-dependent relationship with DR risk. While each 1 µmol/L increase in SUA corresponded to a minimal incremental risk (OR = 1.002), exceeding the threshold of 354.0 µmol/L was associated with a 1.571-fold higher DR risk (95% CI: 1.139–2.099, p = 0.006). Similar threshold-driven effects were observed for CKD.

In the present study, the prevalence of DR among patients with diabetes for at least 5 years was 29.0%, and the prevalence of CKD was 33.1%. It is higher than the reported prevalence in Eastern China [12, 19, 20], which is most likely due to the relatively long duration of diabetes history of the patients included in this study. Additionally, the currently acknowledged risk factors associated with DR or DN [21], including the duration of diabetes, the younger age of onset of diabetes, and higher HbA1c levels were also reported in this study. In our study, 2.2% of participants were prescribed thiazides, which are known to elevate SUA levels. However, their small number limited statistical impact, and no significant differences in SUA levels were observed between users and non-users (median: 355.2 µmol/L vs. 317.0 µmol/L, P = 0.184). Thiazide use was also not associated with DR severity (P = 0.796) or CKD stage (P = 0.705), and adjusting for thiazide use in the regression model did not alter the statistical outcomes. Thus, thiazide use was unlikely to have influenced our findings.

It has been found that SUA levels in patients with T2DM increase with the severity of DR and the decline of renal function [22,23,24,25]. In our study, we also observed a higher level of SUA in patients with more severe DR and relatively high levels of CKD. Of note, there was no significant difference in SUA levels between the CKD2 and CKD3 groups, possibly due to the small sample size of the CKD3 group. Several other studies published have also suggested that SUA may be an independent risk factor for DR [24]. Two large cross-sectional studies reported that SUA is associated with an increased risk of DR or more severe DR [14, 26]. In addition, higher quartiles of SUA were associated with an increased incidence of new-onset DR and progression to NPDR in two prospective cohort studies [22, 27]. Our analyses indicated that higher levels of SUA were identified as independent risk factors for both DR and CKD, consistent with previous research findings. However, there are some studies that presented contrasting results regarding the association between SUA and DR. For example, a large-scale cross-sectional study involving 2961 patients with T2DM demonstrated an association between SUA levels and a higher prevalence of DN instead of DR [12]. Similarly, another cross-sectional study including 2809 patients reported that elevated concentrations of SUA independently increased the risk of DN but not DR [13]. Overall, despite evidence that SUA is associated with the development of DR and CKD, whether elevated SUA is a cause or a consequence of microangiopathy is still controversial. The SUA-CKD association may reflect a vicious cycle where SUA exacerbates renal injury, while declining kidney function further elevates SUA levels. A large number of prospective studies are needed to elucidate the causality.

To investigate the potential impact of SUA on disease mechanisms, various experimental and clinical studies have identified several possible connections between UA and diabetic microangiopathy. Elevated levels of SUA may contribute to the development of diabetic complications by disturbing insulin pathway, triggering inflammation, oxidative stress, and impairing endothelial function [28]. Cassano et al. demonstrated that uric acid exacerbates vascular damage through insulin resistance pathways. This mechanism may partly explain SUA’s association with microvascular complications in diabetes, even after adjusting for traditional risk factors [29]. A cross-sectional study conducted on a large population discovered a correlation between SUA levels and proinflammatory cytokines, including IL-6, TNF-alpha, and CRP, which play a pivotal role in the pathophysiology of diabetic complications [30]. Zhu et al. found that UA increased apoptosis and inflammatory chemokine productions in human retinal endothelial cells exposed to high concentrations of UA. A Similar alteration was observed in animal experiments that rats with hyperuricemia exhibited elevated levels of inflammatory cytokines [31].

Of note, there is sex difference in UA metabolism that males have higher circulating SUA levels than females, as observed in our study. An increase in the risk of cardiovascular death (CVD) and SUA levels was associated with significant intergender differences [32]. However, the occurrence of diabetic complications in men does not always indicate a sex-specific susceptibility to SUA. SUA was reported to affect insulin function in both male and female populations. A recent study has revealed that there is an independent impact of SUA on insulin secretion among female patients, and in male patients, SUA was positively correlated with insulin secretion and insulin resistance index [33]. Clinical studies on DR showed that the sex-specific effect of SUA on microangiopathy is unclear. A cross-sectional study in Japan reported that higher SUA levels were associated with a high risk of developing DR in only males [27]. While another study showed that higher SUA levels are risk factor of VTDR in both sexes, it appears that females exhibited greater susceptibility to high SUA compared to males [14]. Therefore, we conducted a sex‐stratified analysis in this study. The present study indicated a significant positive correlation between SUA levels and DR progression in both males and females after adjustment for potential risk factors, and females seemed to be more susceptible to increasement in SUA levels. At present, the existence of sex differences in SUA for diabetic microangiopathy still needs more researches to be verified. There are arguments regarding the association between SUA and diabetes as well as its complications in females, which may be influenced by their menopausal status. Understanding sex differences at the mechanistic level remains challenging. Sex differences in vascular endothelial cell function and oxidant/antioxidant responses have been shown at the cellular level [34, 35].

Investigating the impact of interventions targeting SUA levels on the progression of DR and nephropathy is another promising avenue. However, there is no consensus on the optimal target for SUA levels in patients with diabetes. UA exhibits physiological solubility up to approximately 380.7 µmol/L (6.4 mg/dL). UA-binding proteins contribute to enhancing solubility to around 416.4µmol/L (7.0 mg/dL) before reaching supersaturation. Beyond this point, crystallization of SUA may occur, leading to the development of hyperuricemia [36]. Typically, hyperuricemia is defined as having SUA levels exceeding 420 µmol/L for males and 360 µmol/L for females. Multiple studies have demonstrated that even when within a normal range, an elevated SUA level is linked to a higher prevalence of diabetic complications after adjusting for confounding factors [27, 37,38,39]. Our results showed that in general population the threshold SUA levels were 354.0 umol/L and 361.0 umol/L for DR and CKD occurrence, respectively. When considering the sex of the patients, it is interesting to note that the identified cutoff values for SUA associated with the worsening of DR were similar, and the SUA thresholds associated with CKD were only slightly higher in men than in women. The previous studies have not provided explicit data regarding the level of SUA that contribute to the development of DR. However, there are researches indicating the threshold values for SUA in CVD and CKD. Virdis et al. identified critical threshold levels for SUA associated with adverse outcomes that 279.6 µmol/L (4.7 mg/dL) for all-cause mortality and 333.1 µmol/L (5.6 mg/dL) for cardiovascular mortality [40]. Another cohort study revealed that in patients with T2DM, SUA levels exceeding 374.85 µmol/L (6.3 mg/dL) independently increased the risk of CKD progression [41]. Although there is no recommendation to initiate SUA-lowering therapy in patients with asymptomatic hyperuricemia [42], it is important to establish an optimal target range of SUA levels in patients with diabetes. On the one hand it helps to reduce the risk of developing diabetic complications, on the other hand, it is beneficial to avoid hypouricemia which has been observed to be associated with decreased renal function and increased mortality [43, 44].

Our study has several limitations. Firstly, due to the cross-sectional design, we cannot determine whether SUA elevation precedes progression of diseases or is a consequence of metabolic dysfunction. Secondly, a history of renin-angiotensin-aldosterone system indicators is absent in this study, which may be one of the important confounding factors that influence estimating the impact of high SUA level. Thirdly, the sample size in this study is not large enough, resulting in a small number of subjects with severer level of DR and CKD. Additionally, the assessment of DME with fundus pictures may be less reliable than the OCT imaging, leading to error of grouping. Lastly, in this study we utilized ROC curve analysis to determine the optimal SUA cut-off values for identifying patients at higher risk of DR and CKD. However, the observed AUC values demonstrated modest predictive accuracy, indicating that SUA alone possesses limited discriminative capacity for these microvascular complications. Additionally, the sensitivity and specificity associated with the identified thresholds were suboptimal, further limiting their clinical applicability. Despite these limitations, our findings suggest that SUA levels may still serve as a potential risk indicator for DR and CKD. Further prospective studies are also warranted to establish whether SUA plays a causal role in the progression of diabetic complications or primarily reflects underlying metabolic and renal dysfunction.

Conclusion

In summary, our study revealed a positive correlation between elevated SUA levels and the progression of both DR and CKD in Chinese individuals with at least a 5-year duration of diabetes, after adjustment for potential confounding factors. The increased risk of DR and worsening was found among subjects with a SUA level higher than 354.0 umol/L and 361.0 umol/L in total population, respectively, with no significant sex-differences. This finding provides evidence and possibilities for future studies to refine SUA risk stratification and treatment interventions in patients with long-term diabetes.

Data availability

No datasets were generated or analysed during the current study.

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Funding

This study was supported by National Natural Science Foundation of China (82171071), Program of Shanghai Academic/Technology Research Leader (21XD1402700).

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Author notes

  1. Hanying Wang, Liping Gu, and Yuhang Ma contributed equally to this study and are considered to be co-first authors.

Authors and Affiliations

  1. Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Jiao Tong University, National Clinical Research Center for Eye Diseases, No. 100 Haining Road, Shanghai, 20080, P. R. China

    Hanying Wang, Xindan Xing, Yuan Qu, Xin Shi, Xinyi Liu, Hancong Wan, Qian Zhu, Yingchen Shen, Chong Chen, Li Su & Kun Liu

  2. Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China

    Liping Gu, Yuhang Ma & Yufan Wang

Authors
  1. Hanying Wang
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Contributions

HW performed the statistical analysis, and was a major contributor in writing the manuscript. LG and YM collected original data and pictures, and LG organized all data. XX, YQ, XS, XL, HW, QZ, YS, CC and LS read the fundus pictures. YW and KL conceived, organized and conducted this clinical study, and KL. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yufan Wang or Kun Liu.

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Wang, H., Gu, L., Ma, Y. et al. High levels of serum uric acid are associated with microvascular complications in patients with long-term diabetes. Diabetol Metab Syndr 17, 106 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13098-025-01656-1

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13098-025-01656-1

Keywords

Diabetology & Metabolic Syndrome

ISSN: 1758-5996

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