Retrospective exploratory analyses on gender differences in determinants for incidence and progression of diabetic retinopathy in Japanese patients with type 2 diabetes mellitus

Nakayama, Yoshiro; Yamaguchi, Satoshi; Shinzato, Yukiko; Okamoto, Susumu; Millman, Jasmine F.; Yamashiro, Kiyoto; Takemoto, Nozomi; Uema, Tsugumi; Arakaki, Koichiro; Higa, Moritake; Koizumi, Hideki; Shimabukuro, Michio; Masuzaki, Hiroaki

doi:10.1507/endocrj.ej20-0630

Cited by 13 publications

(13 citation statements)

References 54 publications

(37 reference statements)

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“…This result was consistent with majority studies [9,11,28]. However, several articles showed opposite result that NPDR group had lower UA level in plasma compared with NDR group [13,37]. One reason may be the coverage error caused by the NPDR patients who lost follow-up due to slow DR progression and normal vision [13].…”

Section: Discussionsupporting

confidence: 88%

“…However, several articles showed opposite result that NPDR group had lower UA level in plasma compared with NDR group [13,37]. One reason may be the coverage error caused by the NPDR patients who lost follow-up due to slow DR progression and normal vision [13]. Another reason is the exclusion of NPDR patients with moderate or severe DME [37].…”

Section: Discussionmentioning

confidence: 99%

“…However, some studies drew opposite conclusions that the serum UA level had no signi cant difference between DR patients and no-DR patients in both T1DM [11] and T2DM [12]. Another study indicated that non-proliferative DR (NPDR) patients in Japan had an even lower serum UA level than that in patients without DR in T2DM [13]. To date, the relationship between UA and DR is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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The association between Uric Acid and Diabetic Retinopathy: Review and meta-analysis

Zhang

2022

Preprint

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Background Diabetic retinopathy (DR) is a serious neuro-microvascular complication of diabetes mellitus (DM), which is due to the disturbance of metabolism. Uric acid (UA) is one of the most important indicators of the occurrence and development of metabolism disorders. Many studies reported UA in DR patients was higher than that in non-DR patients. however, the results are controversial. The purpose of this meta-analysis study was to reveal the relationship between UA level and DR. Method We searched the online electronic database and retrieved all the relevant articles published before March 2022. Demographic data and UA biochemical parameters in different studies were collected. The pooled standard mean deviation (SMD) and its 95% confidence interval (CI) were calculated and meta-analysis was performed. Results A total of 32 articles including 20658 patients were involved in this meta-analysis. The UA levels in DR group was significantly higher than that in non-DM group and NDR group (P = 0.0001; P < 0.00001, respectively). Subgroup analysis showed that there were significant differences in UA level between NPDR and PDR groups (P < 0.00001), NPDR and NDR groups (P = 0.02). In addition, UA levels were significantly higher in DR group comparing NDR group in plasma (P < 0.0001), vitreous (P < 0.00001) and aqueous humor (P < 0.0001) samples. It was also showed UA level was significantly ascended in DR patients no matterT1DM(P < 0.00001) and T2DM (P < 0.00001). Conclusions The UA level is definitely associated with DR severity. Therefore, increased UA concentration maybe a potential biomarker that distinguishes DR from DM, and elevated UA level implied the gradual progress of DR.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The association between Uric Acid and Diabetic Retinopathy: Review and meta-analysis

Zhang

2022

Preprint

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“…Except for three studies ( 28 , 34 , 39 ) that measured UA concentrations using plasma, serum was utilized for the measurement of UA concentrations in other studies. Eleven studies ( 20 , 22 , 29 , 34 , 35 , 37 – 40 , 43 , 44 ) that scored 7 or higher were considered high quality, and others ( 23 , 28 , 30 – 33 , 36 , 41 , 42 , 45 ) scored from 4 to 6, indicating that the overall quality of the studies was acceptable. The participants' characteristics, including age, sex, and BMI, are summarized in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Uric Acid and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Guo

Liu

2022

Front. Public Health

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BackgroundThe relationship between uric acid (UA) and diabetic retinopathy (DR) remains ambiguous, and the results of current studies on the UA levels in patients with DR are conflicting. A meta-analysis was performed to provide a better understanding of the relationship between UA levels and DR.MethodsPubMed, Web of Science, Embase, and the Cochrane Library databases were searched until December 11, 2021 to identify eligible studies, that compared the UA levels of the case group (patients with DR) and control group (controls with diabetes and healthy participants). The weighted mean difference (WMD) with a 95% confidence interval (CI) was used to evaluate the difference in UA levels between the case and control groups.ResultsTwenty-one studies involving 4,340 patients with DR and 8,595 controls (8,029 controls with diabetes and 566 healthy participants) were included in this meta-analysis. We found that patients with DR had significantly higher UA levels than those in the controls with diabetes (WMD = 36.28; 95% CI: 15.68, 56.89; P < 0.001) and healthy participants (WMD = 70.80; 95% CI: 19.85, 121.75; P = 0.006). There was an obvious heterogeneity among the 21 studies (I2 = 97%, P < 0.001). Subgroup analyses of different phases of DR showed that UA levels were significantly increased in participants with proliferative diabetic retinopathy (PDR) (WMD = 46.57; 95% CI: 28.51, 64.63; P < 0.001) than in controls with diabetes; however, the difference is not statistically significant when comparing UA levels in patients with non-proliferative diabetic retinopathy (NPDR) and controls with diabetes (WMD = 22.50; 95% CI: −6.07, 51.08; P = 0.120). In addition, UA levels were higher in participants with a body mass index (BMI) ≥25.0 kg/m2 and over 15 years of diabetes. Univariate meta-regression analysis revealed that BMI (P = 0.007, Adj R2 = 40.12%) and fasting blood glucose (FBG) (P = 0.040, Adj R2 = 29.72%) contributed to between-study heterogeneity.ConclusionsIn conclusion, our study provides evidence that UA levels are higher in patients with DR than those in the controls, but this difference is not statistically significant in the early phases. UA might be a potential biomarker for identifying disease severity in patients with DR, rather than predicting the onset of DR among patients with diabetes. However, more prospective and high-quality clinical evidence is required to confirm these present findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=297708.

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“…Prior research on sex-dependent associations of SUA with diabetes mellitus and its complications has been documented. 22 , 33 , 34 Although hyperuricemia poses an increased risk of developing diabetes mellitus in both sexes, females with hyperuricemia are more likely to develop diabetes than males with hyperuricemia. 35 A Japanese study showed that higher SUA levels are associated with an increased risk of new-onset diabetic retinopathy in male patients but not in female patients.…”

Section: Discussionmentioning

confidence: 99%

Retinal Microvasculature and Choriocapillaris Flow Deficit in Relation to Serum Uric Acid Using Swept-Source Optical Coherence Tomography Angiography

Yue

Chen

et al. 2022

Trans. Vis. Sci. Tech.

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Purpose To explore the relationship between serum uric acid (SUA) and retinochoroidal microcirculation in the Chinese population. Methods This prospective cross-sectional study was conducted among the residents of Guangzhou, southern China. A commercially available optical coherence tomography angiography (OCTA) device was used to obtain the superficial vessel density (SVD) and deep vessel density in the retina and the choriocapillaris flow deficit (CFD) in the macular region. Univariable and multivariable linear regression models were used to assess the association of hyperuricemia and SUA levels with OCTA parameters. Results A total of 638 participants with normal SUA and 296 participants with hyperuricemia were included in the study. Parafoveal SVD was significantly reduced among the participants with hyperuricemia compared to participants with normal SUA ( P < 0.001), while the parafoveal CFD was higher in hyperuricemic participants than those of normal SUA levels ( P = 0.007). After adjusting for potential confounders, greater SUA levels was associated with lower SVD (β = −0.078; P < 0.001) and greater CFD (β = 0.015; P = 0.011). Gender difference analysis indicated that a 10-µmol/L increase in SUA levels among the female participants led to a 0.144 decrease in SVD ( P < 0.001), but it was not statistically significant for the male participants ( P = 0.653). Conclusions An elevated uric acid level and its fluctuations were independently associated with impaired retinal and choroidal microcirculation using OCTA in the study population. Women appear to be more sensitive to high SUA levels than men. Translational Relevance Elevating uric acid concentration may play a role in the development and progression of cardiovascular diseases through microvascular alteration, as demonstrated by OCTA parameters.

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Retrospective exploratory analyses on gender differences in determinants for incidence and progression of diabetic retinopathy in Japanese patients with type 2 diabetes mellitus

Cited by 13 publications

References 54 publications

The association between Uric Acid and Diabetic Retinopathy: Review and meta-analysis

The association between Uric Acid and Diabetic Retinopathy: Review and meta-analysis

Uric Acid and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Retinal Microvasculature and Choriocapillaris Flow Deficit in Relation to Serum Uric Acid Using Swept-Source Optical Coherence Tomography Angiography

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