Modifiable lifestyle, mental health status and diabetic retinopathy in U.S. adults aged 18-64 years with diabetes: a population-based cross-sectional study from NHANES 1999-2018.

BACKGROUND: The relationship between integrated lifestyles, mental status and their impact on overall well-being has attracted considerable attention. This study aimed to evaluate the association between lifestyle factors, depression and diabetic retinopathy (DR) in adults aged 18-64 years. METHODS: A cohort of 3482 participants diagnosed with diabetes was drawn from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999-2018. DR was defined based on self-reported diabetic retinopathy diagnoses by professional physicians, relying on Diabetes Interview Questionnaires. Subgroup analysis was employed to assess lifestyle and psychological factors between participants with DR and those without, both overall and stratified by diabetic duration. Continuous variables were analyzed using the student's t test, while weighted Rao-Scott χ2 test were employed for categorical variables to compare characteristics among the groups. RESULTS: Of the 3482 participants, 767 were diagnosed with diabetic retinopathy, yielding a weighted DR prevalence of 20.8%. Patients with DR exhibited a higher prevalence of heavy drinking, depression, sleep deprivation, and insufficient physical activity compared to those without DR. Furthermore, multivariable logistic regression analysis revealed that sleeping less than 5 h (OR = 3.18, 95%CI: 2.04-4.95, p < 0.001) and depression (OR = 1.35, 95%CI:1.06-1.64, p = 0.025) were associated with a higher risk of DR, while moderate drinking (OR = 0.49, 95%CI: 0.32-0.75, p = 0.001) and greater physical activity (OR = 0.64, 95%CI: 0.35-0.92, p = 0.044) were identified as protective factors. CONCLUSIONS: Adults aged 18-64 years with DR exhibited a higher prevalence of lifestyle-related risk factors and poorer mental health. These findings underscore the need for concerted efforts to promote healthy lifestyles and positive emotional well-being in this population.

Associations of heavy metal exposure with diabetic retinopathy in the U.S. diabetic population: a cross-sectional study.

Background: Mounting evidence suggests a correlation between heavy metals exposure and diabetes. Diabetic retinopathy (DR) is a prevalent and irreversible complication of diabetes that can result in blindness. However, studies focusing on the effects of exposure to heavy metals on DR remain scarce. Thus, this study aimed to investigate the potential correlation between heavy metals exposure and DR. Methods: A total of 1,146 diabetics from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were included in this study. Heavy metal levels were measured via urine testing. Weighted logistic regression, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) were utilized to investigate the potential relationships between exposure to 10 heavy metals and DR. Finally, subgroup analysis was conducted based on the glycemic control status. Results: Among the 1,146 participants, 239 (20.86%) were diagnosed with DR. Those with DR had worse glycemic control and a higher prevalence of chronic kidney disease compared to those without DR. Moreover, both the WQS regression and BKMR models demonstrated a positive relationship between exposure to mixed heavy metals and the risk of DR. The results of weighted logistic regression revealed a positive correlation between cobalt (Co) and antimony (Sb) exposure and the risk of DR (OR = 1.489, 95%CI: 1.064-2.082, p = 0.021; OR = 1.475, 95% CI: 1.084-2.008, p = 0.014), while mercury (Hg) exposure was found to promote DR exclusively in the group with good glycemic control (OR = 1.509, 95% CI: 1.157-1.967, p = 0.003). These findings were corroborated by the results of the RCS analysis. Conclusion: Heavy metal exposure is associated with an increased risk of DR, especially Sb, Co, and Hg exposure. Nevertheless, well-designed prospective studies are warranted to validate these findings.

hsa_circ_0087100/hsa-miR-6743-5p affects Th1 cell differentiation by regulating STAT1 in diabetic retinopathy.

Objective: To elucidate the role of the competitive endogenous RNA (ceRNA) network in immune infiltration of diabetic retinopathy (DR). Methods: We obtained differentially expressed (DE) circRNAs, miRNAs and mRNAs from the Gene Expression Omnibus database. Then, we identified immune infiltration by CIBERSORT and single-sample gene set enrichment analysis and discovered co-expression genes by weighted gene co-expression network analysis. Furthermore, STAT1-mediated Th1 differentiation was determined in DR cell models, DR patients and DR mouse models. Results: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 was involved in immune infiltration of Th1 cells. Aberrant expression of the ceRNA network and STAT1-mediated Th1 differentiation was thus verified in vitro and in vivo. Conclusion: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 may affect Th1 cell differentiation in DR.

TET2-mediated ECM1 hypomethylation promotes the neovascularization in active proliferative diabetic retinopathy.

BACKGROUND: Studies have shown that tet methylcytosine dioxygenase 2 (TET2) is highly expressed in diabetic retinopathy (DR), which reduces the DNA methylation of downstream gene promoters and activates the transcription. Abnormally expressed TET2 and downstream genes in a high-glucose environment are associated with retinal capillary leakage and neovascularization. Here, we investigated the downstream genes of TET2 and its potential association with neovascularization in proliferative diabetic retinopathy (PDR). METHODS: GSE60436, GSE57362, and GSE158333 datasets were analyzed to identify TET2-related hypomethylated and upregulated genes in PDR. Gene expression and promoter methylation of these genes under high glucose treatment were verified. Moreover, TET2 knockdown was used to assess its impact on tube formation and migration in human retinal microvascular endothelial cells (HRMECs), as well as its influence on downstream genes. RESULTS: Our analysis identified three key genes (PARVB, PTPRE, ECM1) that were closely associated with TET2 regulation. High glucose-treated HRMECs exhibited increased expression of TET2 and ECM1 while decreasing the promoter methylation level of ECM1. Subsequently, TET2 knockdown led to decreased migration ability and tube formation function of HRMECs. We further found a decreased expression of PARVB, PTPRE, and ECM1, accompanied by an increase in the promoter methylation of ECM1. CONCLUSIONS: Our findings indicate the involvement of dysregulated TET2 expression in neovascularization by regulating the promoter methylation and transcription of downstream genes (notably ECM1), eventually leading to PDR. The TET2-induced hypomethylation of downstream gene promoters represents a potential therapeutic target and offers a novel perspective on the mechanism underlying neovascularization in PDR.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

Imaging-based body fat distribution and diabetic retinopathy in general US population with diabetes: an NHANES analysis (2003-2006 and 2011-2018).

BACKGROUND: Limited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes. METHODS: The study used a population-based, cross-sectional approach based on the 2003-2006 and 2011-2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR. RESULTS: The prevalence of DR was 22.2, 21.2, and 17.6% among participants with A/G ratios <1.0, 1.0-1.2, and ≥1.2, respectively. After adjusting sex, age, ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level, a higher A/G ratio (≥1.2) was independently associated with decreased odds of DR (odds ratio [OR], 0.565; 95% CI: 0.372-0.858) compared with the A/G ratio of 1.0-1.2. Associations between a higher A/G ratio and DR remained statistically significant after adjusting for BMI (OR, 0.567; 95% CI: 0.373-0.861) and WHtR (OR, 0.586; 95% CI: 0.379-0.907). Moreover, these associations remained statistically significant in analyses using the ethnic-specific tertiles for the A/G ratio. In sex-stratified models, these correlations remained in males. There was a significant inverse association between the A/G ratio and diabetes duration in males, which persisted after multivariable adjustments (p < 0.05). CONCLUSIONS: A novel finding indicates that a higher A/G ratio is associated with a reduced likelihood of DR in males with diabetes. The results from NHANES underscore the importance of considering imaging-based fat distribution as a critical indicator in clinical practice.

Influence of high altitude on choroid thickness, retinal thickness, and myopia: A cross-sectional study comparing adolescents in Shanghai and Tibet.

PURPOSE: This study aimed to explore the influence of high altitude on myopia, macular choroidal thickness (mCT), and macular retinal thickness (mRT) in adolescents. METHODS: Two schools, one in Shanghai (at sea level) and one in Shigatse, Tibet (more than 4000 m above sea level), were selected. Refractive error was measured by an autorefractor instrument and subjective refraction, and mCT and mRT were measured at three concentric circles by optical coherence tomography. Student's t -test, Chi-square test, and multiple linear regression analyses were used to analyze the data. RESULTS: A total of 1114 participants (657 and 457 in Shanghai and Tibet, respectively) were enrolled in this cross-sectional study. The average age of the participants was 18.81 ± 1.10 years, and 44.34% were males. The spherical equivalent (SE) of adolescents in Shanghai was significantly lower than that of adolescents in Tibet (-4.14 ± 2.37 D and -2.12 ± 1.87 D, P < 0.01). The prevalence of myopia and high myopia among adolescents in Shanghai (94.52%, 19.48%) was significantly higher than those among adolescents in Tibet (44.74%, 2.41%) ( P < 0.01). The mCT of Tibetan adolescents was significantly thicker than that of Shanghai adolescents (295.80 ± 62.46 µm and 218.71 ± 61.42 µm, P < 0.01), especially the central mCT. The mRT of Tibetan adolescents was also thicker than that of Shanghai adolescents (301.42 ± 23.26 µm and 281.04 ± 12.24 µm, P < 0.01). CONCLUSIONS: Compared with Shanghai adolescents, the choroid of Tibet adolescents is thicker, and the myopia prevalence is lower. It is speculated that increased altitude is associated with the thickening of mCT and a low myopia prevalence.

The differences of metabolic profiles, socioeconomic status and diabetic retinopathy in U.S. working-age and elderly adults with diabetes: results from NHANES 1999-2018.

AIMS: Controlled metabolic factors and socioeconomic status (SES) was crucial for prevention of diabetic retinopathy (DR). The study aims to assess the metabolic factors control and SES among working-age adults (18-64 years) with diabetes compared to older adults (65 years and older). METHODS: Totals of 6738 participants with self-reported diagnosed diabetes from National Health and Nutrition Examination Survey were included, of whom 3482 were working-age and 3256 were elderly. The prevalence of DR, metabolic factors control, and the impact of SES and diabetic duration on DR was estimated. Subgroup analysis among working-age adults was employed across different diabetic duration and SES level. RESULTS: The prevalence of DR was 20.8% among working-age adults and 20.6% in elderly adults. Further, working-age adults possessed suboptimal control on glycemia (median HbA1c: 7.0% vs. 6.8%, p < 0.001) and lipids (Low-density lipoprotein < 100 mg/dL: 46.4% vs. 63.5%, p < 0.001), but better blood pressure control (< 130/80 mmHg: 53.5% vs. 37.5%, p < 0.001) compared to the elderly, judging based on age-specific control targets. Prolonged diabetic duration didn't improve glycemic and composite factors control. SES like education and income impacted metabolic factors control and adults with higher SES were more likely to control well. Diabetic duration was a significant risk factor (OR = 4.006, 95%CI= (2.752,5.832), p < 0.001) while higher income (OR = 0.590, 95%CI= (0.421,0.826), p = 0.002) and educational level (OR = 0.637, 95%CI= (0.457,0.889), p = 0.008) were protective against DR. CONCLUSIONS: Working-age adults with diabetes demonstrate suboptimal metabolic profile control, especially glycemia and lipids. Additional efforts are needed to improve metabolic factor control and reduce DR risk, particularly for those with longer diabetes duration, less education, and lower incomes.

Prevalence and predictors of developing vision-threatening diabetic retinopathy within the first three years of type 2 diabetes.

Purpose: To investigate the prevalence of diabetic retinopathy (DR) and vision-threatening DR (VTDR) in patients with type 2 diabetes mellitus (T2DM) stratified by the duration of diabetes and to identify the clinical variations and risk factors for VTDR occurring at different stages of T2DM. Methods: This was a retrospective comparative study. Patients were divided into short- (≤3 years), intermediate- (3-7 years), and long-duration (>7 years) groups. All patients were followed-up for DR and VTDR development. Risk factors were explored using logistic regression analysis. Results: A total of,2961 patients were included; among them, 1,036 (35.0%) patients developed DR, and 293 (9.9%) had VTDR. The frequency of VTDR in patients who developed DR in the short-duration group was significantly higher than that in the intermediate-duration group (25.7% vs. 15.0%; p = 0.019), but comparable with that of the long-duration group (25.7% vs. 31.8%; p = 0.138). Patients who developed VTDR within the first 3 years of T2DM were more likely to have a family history of diabetes (p = 0.024), had higher glycated hemoglobin (p = 0.025), were males (p = 0.042), and were notably older at the onset of diabetes (p <0.001) but younger when diagnosed with DR (p <0.001). Moreover, higher glycated hemoglobin (OR = 1.14; 95% CI: 1.00-1.29; p = 0.043) and diabetic nephropathy (DN) (OR = 2.31; 95% CI: 1.08-4.91; p = 0.030) were independent risk factors for developing VTDR during the first 3 years of T2DM. Conclusion: The risk of DR is not high in persons with ≤3 years' duration of T2DM, however, if afflicted, the risk of VTDR should never be neglected. More frequent retinal screening is warranted in patients with newly diagnosed T2DM.