The impact of glycemic control and duration of diabetes on clinical manifestation of ocular surface in middle-aged and elderly type 2 diabetic population

The impact of glycemic control and duration of diabetes on clinical manifestation of ocular surface in middle-aged and elderly type 2 diabetic population | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The impact of glycemic control and duration of diabetes on clinical manifestation of ocular surface in middle-aged and elderly type 2 diabetic population Anran Xuan, Zhongfang Zhang, Qi Li, Wanting Li, Emmanuel Pazo, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6259419/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To investigate the impact of glycemic control and duration of diabetes on clinical manifestation of dry eye in middle-aged and elderly type 2 diabetic population of Tianjin, Northern China. Methods Participants aged over 50 years with type 2 diabetes mellitus (T2DM) were enrolled from December 2019 to August 2022. Systemic and ophthalmic examinations were performed, and diabetic status was screened. Diabetic participants were grouped according to HbA1c levels (HbA1c < 7.8% and HbA1c ≥ 7.8%). In addition, participants were divided into 3 groups according to duration of diabetes (< 10 years, 10–19 years, ≥ 20 years). Regression analyses assessed the potential risk factors. Results 1743 participants were included with a mean age of 64.10 ± 6.70 years old. 433 (24.84%) was diagnosed with dry eye disease (DED) and 1059 (60.76%) had asymptomatic DED. Women were more likely to have DED than men (P < 0.05). LLT (P = 0.020) in two HbA1c groups had statistical difference. Among different durations of diabetes, CFS (P = 0.012), MES (P = 0.001) and MQS (P = 0.045) were significantly significant. There was a statistically significant association between the history of high blood pressure (HBP) and DED (P = 0.042). Meanwhile, people with moderate insomnia had a statistically significant difference in the occurrence of dry eye (P = 0.049). Mild (P = 0.003) and moderate (P = 0.014) anxious populations were more prone to DED. Conclusions In the T2DM population, women had a larger proportion of DED than men. The meibomian gland's morphology and function degraded over time in the diabetes. Diabetics with anxiety and sleep deprivation were more likely to have dry eyes. Health sciences/Health care/Public health/Epidemiology Health sciences/Diseases/Eye diseases/Eye abnormalities Dry eye Type 2 diabetes mellitus Glycemic control Prevalence Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. INTRODUCTION Type 2 diabetes mellitus (T2DM) is a major public health concern in many countries [1] . Over the past three decades, the prevalence of diabetes has more than doubled globally [2] . T2DM is a systemic condition that can lead to various ocular complications, including diabetic retinopathy, cataracts, glaucoma, keratopathy, and dry eye disease (DED) [3, 4] . The International Dry Eye WorkShop (DEWS) defines DED as an abnormality in tear quality, quantity, or dynamics due to any cause, leading to ocular discomfort, visual disturbances, reduced tear film stability, and potential ocular surface damage [5] . A statistically significant association was found between duration of diabetes mellitus (DM) and presence of DED [6] , and therefore it was an important issue that needs further investigations [7] . Prevalence of DED in type 2 diabetics was 43.81% in a tertiary eye care center of Western India [6] .Hospital-based studies in South African and Southern India found that the prevalence of DED was higher in the people with DM than normal people [8, 9] . A study conducted in Yangpu Hospital (Shanghai) revealed T2DM could alter the expression of meibum lipids, thereby aggravating both DED and MGD [10] . A Hong Kong hospital-based study had identified glycated hemoglobin as a significant independent predictor of NITBUT and OSDI in patients with T2DM [11] . In addition, a study in the Shanghai community found 17.5% of T2DM patients were diagnosed with DED [12] . However, epidemiological data on DED in T2DM from Northern China are scarce. Hence, this study aimed to investigate the prevalence and risk factors for dry eye of type 2 diabetic populations aged over 50 years with different duration and HbA1c controlling level, in Beichen District of Tianjin, Northern China. 2. MATERIALS AND METHODS 2.1 Beichen Eye Study (BES) and participants Beichen Eye Study (BES) was a community-based epidemiological survey of eye diseases conducted by the Tianjin Medical University Eye Hospital, which examined the dry eye and related parameters of 1743 T2DM participants with age over 50 years from December 2019 to August 2022. This study used a phased cluster random sampling method, where two streets and two towns were randomly selected in the first stage, and three neighborhood committees or villages were randomly selected from each first-level unit in the second stage. This study obtained the ethical approval from the Ethics Committee of the Tianjin Medical University Eye Hospital (Ethics approval number: 2019ky-22) and registered in Chinese Clinical Trial Registry (ChiCTR2200060578). All participants acknowledged and signed the consent form. Inclusion criteria were as follows: aged 50 or above, diagnosed with T2DM, willingness to comply with study protocol. According to the national diabetes association diabetes clinical standard, the diagnostic criteria for diabetes were revised as: Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L), 2-hour plasma glucose (PG) ≥ 200 mg/dL (11.1 mmol/L) during oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol), random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) or a documented history of T2DM. [13] . All subjects who meet any of the following criteria would be excluded: non- T2DM, had other eye diseases, malignant disease, connective tissue disease, infectious disease, a history of other medical illnesses known to be associated with neuropathy, including auto-immune diseases, treatment with cytotoxic agents and neuro-modulatory medication, neurotoxin exposure, deficiency of vitamin B12, on existing dry eye treatment or using lubricants, had seriously psychiatric disorders; had left the household registration home address; in the past 6 months, not living in the household registration; judging by doctors that the life expectancy was less than 3 months; cannot use the jaw bracket for eye examination, termination of participation or cannot understand the examination process. 2.2 Data collection procedure We collected the following information from the participants: demographic characteristics (age and gender), history of hypertension, daily behaviors (alcohol consumption, tea drinking, smoking), and questionnaire data on insomnia, anxiety, depression, and the Ocular surface disease index (OSDI). Clinical examinations including: Body Mass Index (BMI), Systolic and Diastolic Blood Pressure (SBP and DBP), lipid layer thickness (LLT), partial blink ratio (PBR), meibomian gland loss (MGL), MG expression scores (MES), MG quantity scores (MQS), corneal fluorescein staining (CFS), fluorescein tear film break-up time (FBUT) and Schirmer's I test (SIT). The Meibomian Gland Evaluator (Tear Science Inc, Morrisville, NC) was used to access MES and MQS [14] . LLT and PBR were measured by LipiView® II Ocular Surface Interferometer (Tear Science Inc. Morrisville, NC, USA). MG photograph was captured by LipiView® II Ocular Surface Interferometer then graded by scales [15] . In addition, venous blood samples were collected to measure blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), and triglyceride (TG) levels. The diagnosis of DED was established according to the diagnostic criteria outlined in the Expert Consensus on Dry Eye in China: Examination and Diagnosis (2020): (1) OSDI ≥ 13; and FBUT ≤ 5s, or SIT ≤ 5mm/min (2) OSDI ≥ 13; and 5s < FBUT ≤ 10s, or 5mm/min 5.72 mmol/L and/or TG > 1.70 mmol/L. Hypertension was defined as without the use of antihypertensive medication, three separate measurements on different days are all ≥ 140/90 mmHg. Additionally, asymptomatic DED was defined as the presence of clinical signs meeting the Chinese DED criteria, despite an OSDI score of less than 13 [17, 18] . 2.3 Grouping According to duration of diabetes, subjects were divided into 2 groups: <10 years and ≥ 10 years. According to HbA1c levels, diabetic subjects were divided into two groups: HbA1c levels < 7.8% and HbA1c levels ≥ 7.8% (Fig. 1). 2.4 Statistics Data was analyzed using SPSS 25.0 (SPSS Inc., Chicago, IL, US). Age was expressed as the mean ± standard deviation (SD), and data not conforming to the normal distribution were presented as the median (interquartile range). Categorical variables were compared across groups using the Chi-square test. Age was analyzed using the independent samples t-test and the one-way analysis of variance (ANOVA) F-test. Continuous variables that were not normally distributed or exhibited irregular variance were assessed using the Wilcoxon (Mann-Whitney U) rank-sum test and Kruskal-Wallis H test. Risk factors associated with DED were identified using logistic regression with odds ratios (OR) and 95% confidence intervals (CI) reported. Statistical significance was set at a p -value of less than 0.05. 3. RESULTS 3.1 Prevalence of DED and Asymptomatic DED This study included 1743 subjects with T2DM. Of these, 724 (41.54%) were male and 1019 (58.46%) were female, with a mean age of 64.10 ± 6.70 years old. Among them, 433 (24.84%) was diagnosed with DED, with an average age of 65.04 ± 6.62 years old. Among the study participants, 158 males (21.82%) and 275 females (26.99%) were diagnosed with DED, corresponding to 724 male and 1019 female subjects, respectively. The prevalence of DED was significantly higher in females than in males (P < 0.05). Furthermore, 1059 participants (60.76%) were identified with asymptomatic DED, with a mean age of 63.78 ± 6.78 years. Within this group, asymptomatic DED was present in 458 males (63.26%) and 601 females (58.98%), representing the male and female subjects, respectively. Similar to the overall prevalence, the prevalence of asymptomatic DED was significantly higher in females than in males (P < 0.05) (Table 1 ). In addition, 251 participants did not report dry eye-related clinical symptoms or FBUT ≥ 10s or SIT ≥ 10s. Table 1 Demographic characteristics of the diabetes with DED and asymptomatic DED. Total subjects (n = 1743) DED (n = 433) Asymptomatic DED (n = 1059) Gender Male 724 158 (21.82%) † 458 (63.26%) † Female 1019 275 (26.99%) ‡* 601 (58.98%) ‡* Age (y) 64.10 ± 6.70 65.04 ± 6.62 63.78 ± 6.78 † the ratio of males to all males participants; ‡ the ratio of women to all female participants. *P < 0.05: DED was more common in females than males, and the difference was statistically significant. 3.2 Clinical evaluation in different HbA1c level of diabetes For further analysis the diabetics with different HbA1c levels, subjects were divided into two groups: HbA1c levels < 7.8% and HbA1c levels ≥ 7.8% (Table 2 ). There was no statistically significant difference in gender and age between groups. The LLT of HbA1c ≥ 7.8% group was worse than HbA1c < 7.8% group (P = 0.020). In addition, no statistically significant differences were observed between the two groups in other dry eye measurements: OSDI, PBR, CFS, FBUT, SIT, MGL, MES, MQS (Fig. 2). Table 2 Comparison of ocular surface clinical manifestation between diabetic subjects with different HbA1c levels. HbA1c < 7.8% (n = 1029) HbA1c ≥ 7.8% (n = 714) Statistic value P Gender (Male/Female) 454/575 302/412 0.375 0.540 Age (years) 63.98 ± 6.56 64.13 ± 6.81 -0.376 0.707 OSDI score 6.25 (2.08, 16.67) 6.25 (2.08, 15.00) -0.326 0.744 LLT (nm) 78.25 (63.38, 92.63) 74.00 (59.50, 90.75) -2.321 0.020 * PBR 0.76 (0.50, 1.00) 0.75 (0.50, 1.00) -0.732 0.464 CFS 0.50 (0, 1.00) 0.50 (0, 1.50) -1.663 0.096 FBUT (s) 3.33 (2.33, 5.17) 3.25 (2.33, 5.00) -1.546 0.122 SIT (mm) 8.00 (4.50, 13.00) 7.25 (4.00, 11.13) -1.398 0.162 MGL 3.50 (2.50, 4.00) 3.50 (3.00, 4.50) -0.174 0.862 MES 8.50 (6.00, 11.00) 8.00 (6.00, 11.00) -0.744 0.457 MQS 2.00 (0.50, 2.00) 2.00 (1.00, 2.50) -1.752 0.080 OSDI = Ocular surface disease index, LLT = lipid layer thickness, PBR = partial blink ratio, CFS = Corneal fluorescein staining Scores, FBUT = fluorescein tear film break-up time, SIT = Schirmer's I test, MGL = meibomian gland loss, MES = meibomian gland expression scores, MQS = meibomian gland quantity scores; *P < 0.05. The LLT of HbA1c ≥ 7.8% group was worse than HbA1c < 7.8% group. 3.3 Clinical evaluation in different duration of diabetes Among different durations of diabetes, CFS (P = 0.012), MES (P = 0.001) and MQS (P = 0.045) were significantly significant (Fig. 3). As the process of T2DM, the meibomian gland function and integrity of the corneal epithelium degraded. Data is showed in Table 3 . Table 3 Comparison of ocular surface clinical manifestation between diabetic subjects with different duration of diabetes. < 10 years (n = 854) 10-19years (n = 580) ≥ 20 years (n = 309) Statistic value P Gender (Male/Female) 364/490 266/314 147/162 1.185 0.553 Age (years) 64.27 ± 6.22 64.76 ± 6.50 68.55 ± 7.76 19.865 < 0.001 OSDI score 8.33 (4.17, 16.67) 7.00 (3.00, 12.75) 8.00 (3.25, 20.63) 6.000 0.050 LLT (nm) 76.50 (61.00, 94.00) 76.50 (57.50, 95.25) 78.50 (60.00, 92.50) 2.694 0.260 PBR 0.78 (0.50, 1.00) 0.70 (0.43, 1.00) 0.67 (0.33, 1.00) 2.341 0.310 CFS 0 (0, 1.00) 0.50 (0, 1.50) 0.50 (0, 2.00) 8.813 0.012 * FBUT (s) 4.00 (3.00, 5.67) 4.00 (3.00, 5.84) 4.00 (2.54, 6.00) 0.413 0.813 SIT (mm) 7.50 (4.50, 12.00) 8.00 (4.50, 12.5) 7.00 (4.63, 10.00) 1.206 0.547 MGL 3.00 (2.50, 4.00) 3.00 (2.00, 4.00) 3.00 (2.00, 4.00) 2.342 0.310 MES 7.00 (5.00, 10.00) 7.50 (6.00, 10.00) 8.00 (6.00, 10.50) 13.771 0.001 * MQS 1.00 (0, 2.00) 1.00 (0, 2.00) 1.00 (0, 2.00) 6.214 0.045 * OSDI = Ocular surface disease index, LLT = lipid layer thickness, PBR = partial blink ratio, CFS = Corneal fluorescein staining Scores, FBUT = fluorescein tear film break-up time, SIT = Schirmer's I test, MGL = meibomian gland loss, MES = meibomian gland expression scores, MQS = meibomian gland quantity scores; *P < 0.05. CFS, MES and MQS were significantly significant between three groups. As the process of T2DM, the meibomian gland function and integrity of the corneal epithelium degraded. 3.4 Risk factors for DED Logistic regression analysis was conducted to assess potential influencing factors of DED, with results presented in Fig. 4. A statistically significant association was identified between HBP and DED (P = 0.042). Compared to non- anxiety populations, mild (P = 0.003) and moderate (P = 0.014) anxious populations were more prone to DED. Meanwhile, compared with those who did not suffer from insomnia, individuals with moderate insomnia exhibited a statistically significant difference in the occurrence of dry eye (P = 0.049). 3.5 Comparison of ocular surface clinical manifestation between diabetic DED and diabetes population MGL, MES and MQS had statistical differences between diabetic DED and diabetes population (Fig. 5). Thus, the function of meibomian glands were more susceptible to damage in diabetic DED. 4. DISCUSSION This study was the community-based epidemiological survey of DED in Beichen District, Northern China. This study found the prevalence of DED in T2DM was 33.70%, coinciding to the previous prevalence of DED (17.5–70%) [12, 19–21] . In addition, studies had indicated that women were more prone to experiencing DED compared to men [22, 23] . Women also exhibited a higher prevalence of DED compared to males among individuals with T2DM in this survey. Moreover, the study identified 66.30% of the participants had asymptomatic DED, while the prevalence of asymptomatic DED in female was significantly difference compared to males among individuals with T2DM. T2DM patients were more likely to suffer asymptomatic DED. The decreased sensitivity of the cornea due to diabetes may related to this result [8, 12] . HbA1c was considered as the most important tool for the assessment of DM control and a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM [11, 24, 25] . Higher levels of glycosylated hemoglobin HbA1c was significantly associated with the presence of DED [12] . This survey found LLT had significant difference between two serum HbA1c level groups. No significant correlation between serum HbA1c level and other ocular surface parameters such as OSDI score, PBR, CFS, FBUT, SIT, MGL, MES and MQS. Therefore, good control of the HbA1c level was beneficial to the function of the meibomian glands. A Longer duration of diabetes was associated with major symptoms and pathological changes in the MGs, as well asymptomatic dry eye [20, 26] . Prolonged hyperglycemia resulted in notable structural alterations and progressive decline of MG epithelial cells, indicating that hyperglycemia was the underlying factor behind meibomian gland dysfunction (MGD) in individuals with diabetes [27] . Studies had revealed more significant morphological and cytological changes and dysfunction in MGs with compared with nondiabetic patients [28, 29] . The diabetic group presented significant changes in lid and tear function, which were associated with evaporative DED and strongly correlated with MG inflammation and obstruction. This study found that as the duration of diabetes increased, CFS, MES, MQS scores all got worse. Previous studies had shown that female, advanced age, poor diabetic control, excessive psychological stress and decreased corneal sensitivity were positively associated with the occurrence of DED in patients with DM [12, 30–32] . In addition, corneal sensitivity and depressive symptom were associated factors for the incidence of DED in DM [33] .This study found that HBP history in diabetic was positively correlated with the occurrence of DED. This may be related to the use of related antihypertensive medications or vascular lesions associated with hypertension. Meanwhile, abnormal lipid metabolism can cause abnormal lipid composition of meibomian glands, meibomian gland obstruction and other ocular surface abnormalities, resulting in a significant decrease in tear film stability and dry eye symptoms [34, 35] . Sleep disorders were viewed as a prevalent and serious comorbidity in DED and insomnia severity was positively associated with DE symptom severity [36–38] . In this study, compared with those who did not suffer from insomnia, people who had moderate insomnia had a statistically significant difference in the occurrence of dry eye Therefore, insomnia may be a contributing factor to the development of diabetic with dry eye. In addition, compared to non- anxiety populations, mild and moderate anxious populations were more prone to DED. It was important to note that this study had certain limitations. The cross-sectional survey constrained the capacity to establish causality between research variables. In addition, we could not determine the response rate of the study, which may lead to a non-response bias. Due to the extended duration of the study, we refrained from calculating the environmental temperature, humidity and air quality levels, as these factors had been reported to affect symptoms of DED [39, 40] . Consequently, the conclusions could not be overtly generalized. 5. CONCLUSION In this study, women exhibited a higher prevalence of DED and asymptomatic DED compared to males among individuals with T2DM. This study suggested MGD was the main manifestation in T2DM population. In addition, HBP history, anxiety and insomnia were related to the occurrence of DED. Thus, regular ophthalmological exams were recommended with an emphasis on meibomian gland health in diabetic patients. Declarations Declaration of competing interest All authors have no conflict of interest to declare. Funding This study was supported by Open Project of Tianjin Key Laboratory of Retinal Functions and Diseases (2023tjswmm002), Tianjin Science and Technology Bureau (21JCZDJC01010), and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A). Acknowledgements This study has not been presented previously. References Shih KC, Lam KS, Tong L. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutrition & diabetes 2017; 7(3):e251. 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Xuan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIie3PsUoDQRCA4VkO7pqDtHMIiY8wYSEqSJ5lh0Cq1JJCdI+DTSP6AIrPkMp6ZSHVktrOW32BlLHzEkh7d6Xg/sWyxXwMAxCL/cmEhhqAICvLWi1xOOhF1IHkzlHtL2Wh+yw6EpzPi2CWvO4ig2dX1mymkuyCkF9RrCEJXx8tBLdcEZvZhKwn4jdMLiCVctG2xguDbOw1vT+Qakh6pfP0rI2MvFjtj8TlZPkFm7eDULMFGjKhTcqaNWInGXtRodrOZOETB2qDVFQdtwx9Fna7m+n48TOsfva3d/dPWRW+W88/dW5Pv6TP+KGR7jsZi8Vi/65fRLlRSsFDbewAAAAASUVORK5CYII=","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":true,"prefix":"","firstName":"Anran","middleName":"","lastName":"Xuan","suffix":""},{"id":436901174,"identity":"ba663777-0777-4eaa-aa15-973d160f4de8","order_by":1,"name":"Zhongfang Zhang","email":"","orcid":"","institution":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Ey","correspondingAuthor":false,"prefix":"","firstName":"Zhongfang","middleName":"","lastName":"Zhang","suffix":""},{"id":436901175,"identity":"0c7db71f-af31-40cb-8989-cfe26b8b7bee","order_by":2,"name":"Qi Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Li","suffix":""},{"id":436901176,"identity":"eb5a582d-9179-455e-8c7e-837bef214a18","order_by":3,"name":"Wanting Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Wanting","middleName":"","lastName":"Li","suffix":""},{"id":436901177,"identity":"e2432d37-704c-480c-add9-80f2cfd09772","order_by":4,"name":"Emmanuel Pazo","email":"","orcid":"https://orcid.org/0000-0002-0848-827X","institution":"TIANJIN MEDICAL UNIVERSITY EYE HOSPITAL","correspondingAuthor":false,"prefix":"","firstName":"Emmanuel","middleName":"","lastName":"Pazo","suffix":""},{"id":436901178,"identity":"55e54a0c-0e04-4983-9f7a-2a14d9ba3b56","order_by":5,"name":"Fei Li","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Li","suffix":""},{"id":436901179,"identity":"e8e80bb9-8033-4303-8942-860e42b18fbe","order_by":6,"name":"Yue Huang","email":"","orcid":"","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Huang","suffix":""},{"id":436901180,"identity":"24994c69-33d2-4f27-a21b-82a5b47e3754","order_by":7,"name":"Ruibo Yang","email":"","orcid":"https://orcid.org/0000-0001-5085-6497","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ruibo","middleName":"","lastName":"Yang","suffix":""},{"id":436901181,"identity":"b01b67f3-ee7f-41b8-a3ad-f6f872b4f6ab","order_by":8,"name":"Hui Liu","email":"","orcid":"","institution":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Ey","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Liu","suffix":""},{"id":436901182,"identity":"6644fd2d-c778-4e72-ad3f-e0e6098b7994","order_by":9,"name":"Xiaorong Li","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Xiaorong","middleName":"","lastName":"Li","suffix":""},{"id":436901183,"identity":"094e986f-e6dd-4305-b36a-2ab1c024e2db","order_by":10,"name":"shaozhen Zhao","email":"","orcid":"https://orcid.org/0000-0001-7646-2699","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"shaozhen","middleName":"","lastName":"Zhao","suffix":""},{"id":436901184,"identity":"027147f3-b462-410a-acc6-4aa8eafba19e","order_by":11,"name":"Chen Zhang","email":"","orcid":"https://orcid.org/0000-0001-9078-8695","institution":"Tianjin Medical University Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chen","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-03-19 08:25:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6259419/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6259419/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81699914,"identity":"7c39d46a-d452-4b29-886d-554b95404763","added_by":"auto","created_at":"2025-04-30 13:04:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22508,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/d14785ae5ae04f25f71f24f8.png"},{"id":81699740,"identity":"3060df53-c57f-441b-8539-ccb5077b1fa0","added_by":"auto","created_at":"2025-04-30 13:03:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":520484,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/5f12e4dded6886d7b0fb3614.png"},{"id":81699887,"identity":"17911a87-407d-4009-9b87-b2a2776d8b64","added_by":"auto","created_at":"2025-04-30 13:04:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":577499,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/26c8c4682ffb3ed6024cae5d.png"},{"id":81699766,"identity":"bc0bccc1-4e16-482d-b675-c6de6f295b45","added_by":"auto","created_at":"2025-04-30 13:03:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":180016,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure47.png","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/80d1e8e52c85338b7385aff9.png"},{"id":81699998,"identity":"fc2cc0f0-1024-4413-80cd-caeed0c3e71d","added_by":"auto","created_at":"2025-04-30 13:04:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":36515,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/e38801ea695237614e93c6ae.png"},{"id":88523315,"identity":"38d9cdc4-fba4-4377-a43a-644818bf0eec","added_by":"auto","created_at":"2025-08-07 10:04:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1498062,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6259419/v1/33affd61-c0a5-404c-bf3a-c5131239dd8c.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"The impact of glycemic control and duration of diabetes on clinical manifestation of ocular surface in middle-aged and elderly type 2 diabetic population","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is a major public health concern in many countries \u003csup\u003e[1]\u003c/sup\u003e. Over the past three decades, the prevalence of diabetes has more than doubled globally \u003csup\u003e[2]\u003c/sup\u003e. T2DM is a systemic condition that can lead to various ocular complications, including diabetic retinopathy, cataracts, glaucoma, keratopathy, and dry eye disease (DED) \u003csup\u003e[3, 4]\u003c/sup\u003e. The International Dry Eye WorkShop (DEWS) defines DED as an abnormality in tear quality, quantity, or dynamics due to any cause, leading to ocular discomfort, visual disturbances, reduced tear film stability, and potential ocular surface damage \u003csup\u003e[5]\u003c/sup\u003e. A statistically significant association was found between duration of diabetes mellitus (DM) and presence of DED \u003csup\u003e[6]\u003c/sup\u003e, and therefore it was an important issue that needs further investigations \u003csup\u003e[7]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePrevalence of DED in type 2 diabetics was 43.81% in a tertiary eye care center of Western India \u003csup\u003e[6]\u003c/sup\u003e.Hospital-based studies in South African and Southern India found that the prevalence of DED was higher in the people with DM than normal people \u003csup\u003e[8, 9]\u003c/sup\u003e. A study conducted in Yangpu Hospital (Shanghai) revealed T2DM could alter the expression of meibum lipids, thereby aggravating both DED and MGD \u003csup\u003e[10]\u003c/sup\u003e. A Hong Kong hospital-based study had identified glycated hemoglobin as a significant independent predictor of NITBUT and OSDI in patients with T2DM \u003csup\u003e[11]\u003c/sup\u003e. In addition, a study in the Shanghai community found 17.5% of T2DM patients were diagnosed with DED \u003csup\u003e[12]\u003c/sup\u003e. However, epidemiological data on DED in T2DM from Northern China are scarce. Hence, this study aimed to investigate the prevalence and risk factors for dry eye of type 2 diabetic populations aged over 50 years with different duration and HbA1c controlling level, in Beichen District of Tianjin, Northern China.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Beichen Eye Study (BES) and participants\u003c/h2\u003e \u003cp\u003eBeichen Eye Study (BES) was a community-based epidemiological survey of eye diseases conducted by the Tianjin Medical University Eye Hospital, which examined the dry eye and related parameters of 1743 T2DM participants with age over 50 years from December 2019 to August 2022. This study used a phased cluster random sampling method, where two streets and two towns were randomly selected in the first stage, and three neighborhood committees or villages were randomly selected from each first-level unit in the second stage.\u003c/p\u003e \u003cp\u003e This study obtained the ethical approval from the Ethics Committee of the Tianjin Medical University Eye Hospital (Ethics approval number: 2019ky-22) and registered in Chinese Clinical Trial Registry (ChiCTR2200060578). All participants acknowledged and signed the consent form.\u003c/p\u003e \u003cp\u003eInclusion criteria were as follows: aged 50 or above, diagnosed with T2DM, willingness to comply with study protocol. According to the national diabetes association diabetes clinical standard, the diagnostic criteria for diabetes were revised as: Fasting plasma glucose (FPG)\u0026thinsp;\u0026ge;\u0026thinsp;126 mg/dL (7.0 mmol/L), 2-hour plasma glucose (PG)\u0026thinsp;\u0026ge;\u0026thinsp;200 mg/dL (11.1 mmol/L) during oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c)\u0026thinsp;\u0026ge;\u0026thinsp;6.5% (48 mmol/mol), random plasma glucose\u0026thinsp;\u0026ge;\u0026thinsp;200 mg/dL (11.1 mmol/L) or a documented history of T2DM. \u003csup\u003e[13]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAll subjects who meet any of the following criteria would be excluded: non- T2DM, had other eye diseases, malignant disease, connective tissue disease, infectious disease, a history of other medical illnesses known to be associated with neuropathy, including auto-immune diseases, treatment with cytotoxic agents and neuro-modulatory medication, neurotoxin exposure, deficiency of vitamin B12, on existing dry eye treatment or using lubricants, had seriously psychiatric disorders; had left the household registration home address; in the past 6 months, not living in the household registration; judging by doctors that the life expectancy was less than 3 months; cannot use the jaw bracket for eye examination, termination of participation or cannot understand the examination process.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data collection procedure\u003c/h2\u003e \u003cp\u003eWe collected the following information from the participants: demographic characteristics (age and gender), history of hypertension, daily behaviors (alcohol consumption, tea drinking, smoking), and questionnaire data on insomnia, anxiety, depression, and the Ocular surface disease index (OSDI). Clinical examinations including: Body Mass Index (BMI), Systolic and Diastolic Blood Pressure (SBP and DBP), lipid layer thickness (LLT), partial blink ratio (PBR), meibomian gland loss (MGL), MG expression scores (MES), MG quantity scores (MQS), corneal fluorescein staining (CFS), fluorescein tear film break-up time (FBUT) and Schirmer's I test (SIT). The Meibomian Gland Evaluator (Tear Science Inc, Morrisville, NC) was used to access MES and MQS \u003csup\u003e[14]\u003c/sup\u003e. LLT and PBR were measured by LipiView\u0026reg; II Ocular Surface Interferometer (Tear Science Inc. Morrisville, NC, USA). MG photograph was captured by LipiView\u0026reg; II Ocular Surface Interferometer then graded by scales \u003csup\u003e[15]\u003c/sup\u003e. In addition,\u003c/p\u003e \u003cp\u003evenous blood samples were collected to measure blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), and triglyceride (TG) levels.\u003c/p\u003e \u003cp\u003eThe diagnosis of DED was established according to the diagnostic criteria outlined in the Expert Consensus on Dry Eye in China: Examination and Diagnosis (2020): (1) OSDI\u0026thinsp;\u0026ge;\u0026thinsp;13; and FBUT\u0026thinsp;\u0026le;\u0026thinsp;5s, or SIT\u0026thinsp;\u0026le;\u0026thinsp;5mm/min (2) OSDI\u0026thinsp;\u0026ge;\u0026thinsp;13; and 5s\u0026thinsp;\u0026lt;\u0026thinsp;FBUT\u0026thinsp;\u0026le;\u0026thinsp;10s, or 5mm/min\u0026thinsp;\u0026lt;\u0026thinsp;SIT\u0026thinsp;\u0026le;\u0026thinsp;10mm/min; and corneal staining\u0026thinsp;\u0026ge;\u0026thinsp;5 dots \u003csup\u003e[16]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHyperlipidemia was defined as TC\u0026thinsp;\u0026gt;\u0026thinsp;5.72 mmol/L and/or TG\u0026thinsp;\u0026gt;\u0026thinsp;1.70 mmol/L. Hypertension was defined as without the use of antihypertensive medication, three separate measurements on different days are all \u0026ge;\u0026thinsp;140/90 mmHg.\u003c/p\u003e \u003cp\u003eAdditionally, asymptomatic DED was defined as the presence of clinical signs meeting the Chinese DED criteria, despite an OSDI score of less than 13 \u003csup\u003e[17, 18]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Grouping\u003c/h2\u003e \u003cp\u003eAccording to duration of diabetes, subjects were divided into 2 groups: \u0026lt;10 years and \u0026ge;\u0026thinsp;10 years. According to HbA1c levels, diabetic subjects were divided into two groups: HbA1c levels\u0026thinsp;\u0026lt;\u0026thinsp;7.8% and HbA1c levels\u0026thinsp;\u0026ge;\u0026thinsp;7.8% (Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistics\u003c/h2\u003e \u003cp\u003eData was analyzed using SPSS 25.0 (SPSS Inc., Chicago, IL, US). Age was expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), and data not conforming to the normal distribution were presented as the median (interquartile range). Categorical variables were compared across groups using the Chi-square test. Age was analyzed using the independent samples t-test and the one-way analysis of variance (ANOVA) F-test. Continuous variables that were not normally distributed or exhibited irregular variance were assessed using the Wilcoxon (Mann-Whitney U) rank-sum test and Kruskal-Wallis H test.\u003c/p\u003e \u003cp\u003eRisk factors associated with DED were identified using logistic regression with odds ratios (OR) and 95% confidence intervals (CI) reported. Statistical significance was set at a \u003cem\u003ep\u003c/em\u003e-value of less than 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Prevalence of DED and Asymptomatic DED\u003c/h2\u003e \u003cp\u003eThis study included 1743 subjects with T2DM. Of these, 724 (41.54%) were male and 1019 (58.46%) were female, with a mean age of 64.10\u0026thinsp;\u0026plusmn;\u0026thinsp;6.70 years old. Among them, 433 (24.84%) was diagnosed with DED, with an average age of 65.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62 years old. Among the study participants, 158 males (21.82%) and 275 females (26.99%) were diagnosed with DED, corresponding to 724 male and 1019 female subjects, respectively. The prevalence of DED was significantly higher in females than in males (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eFurthermore, 1059 participants (60.76%) were identified with asymptomatic DED, with a mean age of 63.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.78 years. Within this group, asymptomatic DED was present in 458 males (63.26%) and 601 females (58.98%), representing the male and female subjects, respectively. Similar to the overall prevalence, the prevalence of asymptomatic DED was significantly higher in females than in males (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition, 251 participants did not report dry eye-related clinical symptoms or FBUT\u0026thinsp;\u0026ge;\u0026thinsp;10s or SIT\u0026thinsp;\u0026ge;\u0026thinsp;10s.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of the diabetes with DED and asymptomatic DED.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTotal subjects\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1743)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eDED\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;433)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAsymptomatic DED\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1059)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e724\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e158 (21.82%) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e458 (63.26%) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e1019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e275 (26.99%) \u003csup\u003e\u0026Dagger;*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e601 (58.98%) \u003csup\u003e\u0026Dagger;*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e64.10\u0026thinsp;\u0026plusmn;\u0026thinsp;6.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.04\u0026thinsp;\u0026plusmn;\u0026thinsp;6.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e\u0026dagger;\u003c/sup\u003ethe ratio of males to all males participants; \u003csup\u003e\u0026Dagger;\u003c/sup\u003e the ratio of women to all female participants. *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05: DED was more common in females than males, and the difference was statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Clinical evaluation in different HbA1c level of diabetes\u003c/h2\u003e \u003cp\u003eFor further analysis the diabetics with different HbA1c levels, subjects were divided into two groups: HbA1c levels\u0026thinsp;\u0026lt;\u0026thinsp;7.8% and HbA1c levels\u0026thinsp;\u0026ge;\u0026thinsp;7.8% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There was no statistically significant difference in gender and age between groups. The LLT of HbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7.8% group was worse than HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7.8% group (P\u0026thinsp;=\u0026thinsp;0.020). In addition, no statistically significant differences were observed between the two groups in other dry eye measurements: OSDI, PBR, CFS, FBUT, SIT, MGL, MES, MQS (Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of ocular surface clinical manifestation between diabetic subjects with different HbA1c levels.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7.8%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1029)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7.8%\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;714)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStatistic value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (Male/Female)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e454/575\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e302/412\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.540\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63.98\u0026thinsp;\u0026plusmn;\u0026thinsp;6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.13\u0026thinsp;\u0026plusmn;\u0026thinsp;6.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOSDI score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.25 (2.08, 16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.25 (2.08, 15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.326\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.744\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLLT (nm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.25 (63.38, 92.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.00 (59.50, 90.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePBR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.76 (0.50, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75 (0.50, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCFS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.50 (0, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50 (0, 1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFBUT (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.33 (2.33, 5.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.25 (2.33, 5.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSIT (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.00 (4.50, 13.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.25 (4.00, 11.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.398\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMGL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.50 (2.50, 4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.50 (3.00, 4.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMES\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.50 (6.00, 11.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00 (6.00, 11.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.744\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMQS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.00 (0.50, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00 (1.00, 2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOSDI\u0026thinsp;=\u0026thinsp;Ocular surface disease index, LLT\u0026thinsp;=\u0026thinsp;lipid layer thickness, PBR\u0026thinsp;=\u0026thinsp;partial blink ratio, CFS\u0026thinsp;=\u0026thinsp;Corneal fluorescein staining Scores, FBUT\u0026thinsp;=\u0026thinsp;fluorescein tear film break-up time, SIT\u0026thinsp;=\u0026thinsp;Schirmer's I test, MGL\u0026thinsp;=\u0026thinsp;meibomian gland loss, MES\u0026thinsp;=\u0026thinsp;meibomian gland expression scores, MQS\u0026thinsp;=\u0026thinsp;meibomian gland quantity scores; *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eThe LLT of HbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7.8% group was worse than HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7.8% group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Clinical evaluation in different duration of diabetes\u003c/h2\u003e \u003cp\u003eAmong different durations of diabetes, CFS (P\u0026thinsp;=\u0026thinsp;0.012), MES (P\u0026thinsp;=\u0026thinsp;0.001) and MQS (P\u0026thinsp;=\u0026thinsp;0.045) were significantly significant (Fig.\u0026nbsp;3). As the process of T2DM, the meibomian gland function and integrity of the corneal epithelium degraded. Data is showed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of ocular surface clinical manifestation between diabetic subjects with different duration of diabetes.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10 years\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;854)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10-19years\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;580)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;20 years\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;309)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStatistic value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (Male/Female)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e364/490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e266/314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147/162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.553\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.27\u0026thinsp;\u0026plusmn;\u0026thinsp;6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.76\u0026thinsp;\u0026plusmn;\u0026thinsp;6.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.55\u0026thinsp;\u0026plusmn;\u0026thinsp;7.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.865\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOSDI score\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.33 (4.17, 16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.00 (3.00, 12.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.00 (3.25, 20.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLLT (nm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76.50 (61.00, 94.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.50 (57.50, 95.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.50 (60.00, 92.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePBR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.78 (0.50, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.70 (0.43, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67 (0.33, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.310\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCFS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50 (0, 1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.50 (0, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.813\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFBUT (s)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.00 (3.00, 5.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.00 (3.00, 5.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.00 (2.54, 6.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSIT (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.50 (4.50, 12.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.00 (4.50, 12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.00 (4.63, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMGL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.00 (2.50, 4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.00 (2.00, 4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.00 (2.00, 4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.342\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.310\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMES\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.00 (5.00, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.50 (6.00, 10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.00 (6.00, 10.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.771\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMQS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 (0, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (0, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00 (0, 2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.045\u003c/b\u003e*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOSDI\u0026thinsp;=\u0026thinsp;Ocular surface disease index, LLT\u0026thinsp;=\u0026thinsp;lipid layer thickness, PBR\u0026thinsp;=\u0026thinsp;partial blink ratio, CFS\u0026thinsp;=\u0026thinsp;Corneal fluorescein staining Scores, FBUT\u0026thinsp;=\u0026thinsp;fluorescein tear film break-up time, SIT\u0026thinsp;=\u0026thinsp;Schirmer's I test, MGL\u0026thinsp;=\u0026thinsp;meibomian gland loss, MES\u0026thinsp;=\u0026thinsp;meibomian gland expression scores, MQS\u0026thinsp;=\u0026thinsp;meibomian gland quantity scores; *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eCFS, MES and MQS were significantly significant between three groups. As the process of T2DM, the meibomian gland function and integrity of the corneal epithelium degraded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Risk factors for DED\u003c/h2\u003e \u003cp\u003eLogistic regression analysis was conducted to assess potential influencing factors of DED, with results presented in Fig.\u0026nbsp;4. A statistically significant association was identified between HBP and DED (P\u0026thinsp;=\u0026thinsp;0.042). Compared to non- anxiety populations, mild (P\u0026thinsp;=\u0026thinsp;0.003) and moderate (P\u0026thinsp;=\u0026thinsp;0.014) anxious populations were more prone to DED. Meanwhile, compared with those who did not suffer from insomnia, individuals with moderate insomnia exhibited a statistically significant difference in the occurrence of dry eye (P\u0026thinsp;=\u0026thinsp;0.049).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Comparison of ocular surface clinical manifestation between diabetic DED and diabetes population\u003c/h2\u003e \u003cp\u003eMGL, MES and MQS had statistical differences between diabetic DED and diabetes population (Fig.\u0026nbsp;5). Thus, the function of meibomian glands were more susceptible to damage in diabetic DED.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThis study was the community-based epidemiological survey of DED in Beichen District, Northern China. This study found the prevalence of DED in T2DM was 33.70%, coinciding to the previous prevalence of DED (17.5–70%) \u003csup\u003e[12, 19–21]\u003c/sup\u003e. In addition, studies had indicated that women were more prone to experiencing DED compared to men \u003csup\u003e[22, 23]\u003c/sup\u003e. Women also exhibited a higher prevalence of DED compared to males among individuals with T2DM in this survey. Moreover, the study identified 66.30% of the participants had asymptomatic DED, while the prevalence of asymptomatic DED in female was significantly difference compared to males among individuals with T2DM. T2DM patients were more likely to suffer asymptomatic DED. The decreased sensitivity of the cornea due to diabetes may related to this result \u003csup\u003e[8, 12]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHbA1c was considered as the most important tool for the assessment of DM control and a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM \u003csup\u003e[11, 24, 25]\u003c/sup\u003e. Higher levels of glycosylated hemoglobin HbA1c was significantly associated with the presence of DED \u003csup\u003e[12]\u003c/sup\u003e. This survey found LLT had significant difference between two serum HbA1c level groups. No significant correlation between serum HbA1c level and other ocular surface parameters such as OSDI score, PBR, CFS, FBUT, SIT, MGL, MES and MQS. Therefore, good control of the HbA1c level was beneficial to the function of the meibomian glands.\u003c/p\u003e \u003cp\u003eA Longer duration of diabetes was associated with major symptoms and pathological changes in the MGs, as well asymptomatic dry eye \u003csup\u003e[20, 26]\u003c/sup\u003e. Prolonged hyperglycemia resulted in notable structural alterations and progressive decline of MG epithelial cells, indicating that hyperglycemia was the underlying factor behind meibomian gland dysfunction (MGD) in individuals with diabetes \u003csup\u003e[27]\u003c/sup\u003e. Studies had revealed more significant morphological and cytological changes and dysfunction in MGs with compared with nondiabetic patients \u003csup\u003e[28, 29]\u003c/sup\u003e. The diabetic group presented significant changes in lid and tear function, which were associated with evaporative DED and strongly correlated with MG inflammation and obstruction. This study found that as the duration of diabetes increased, CFS, MES, MQS scores all got worse.\u003c/p\u003e \u003cp\u003ePrevious studies had shown that female, advanced age, poor diabetic control, excessive psychological stress and decreased corneal sensitivity were positively associated with the occurrence of DED in patients with DM \u003csup\u003e[12, 30–32]\u003c/sup\u003e. In addition, corneal sensitivity and depressive symptom were associated factors for the incidence of DED in DM \u003csup\u003e[33]\u003c/sup\u003e.This study found that HBP history in diabetic was positively correlated with the occurrence of DED. This may be related to the use of related antihypertensive medications or vascular lesions associated with hypertension. Meanwhile, abnormal lipid metabolism can cause abnormal lipid composition of meibomian glands, meibomian gland obstruction and other ocular surface abnormalities, resulting in a significant decrease in tear film stability and dry eye symptoms \u003csup\u003e[34, 35]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSleep disorders were viewed as a prevalent and serious comorbidity in DED and insomnia severity was positively associated with DE symptom severity \u003csup\u003e[36–38]\u003c/sup\u003e. In this study, compared with those who did not suffer from insomnia, people who had moderate insomnia had a statistically significant difference in the occurrence of dry eye Therefore, insomnia may be a contributing factor to the development of diabetic with dry eye. In addition, compared to non- anxiety populations, mild and moderate anxious populations were more prone to DED.\u003c/p\u003e \u003cp\u003eIt was important to note that this study had certain limitations. The cross-sectional survey constrained the capacity to establish causality between research variables. In addition, we could not determine the response rate of the study, which may lead to a non-response bias. Due to the extended duration of the study, we refrained from calculating the environmental temperature, humidity and air quality levels, as these factors had been reported to affect symptoms of DED \u003csup\u003e[39, 40]\u003c/sup\u003e. Consequently, the conclusions could not be overtly generalized.\u003c/p\u003e "},{"header":"5. CONCLUSION","content":"\u003cp\u003eIn this study, women exhibited a higher prevalence of DED and asymptomatic DED compared to males among individuals with T2DM. This study suggested MGD was the main manifestation in T2DM population. In addition, HBP history, anxiety and insomnia were related to the occurrence of DED. Thus, regular ophthalmological exams were recommended with an emphasis on meibomian gland health in diabetic patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclaration of competing interest\u003c/h2\u003e \u003cp\u003eAll authors have no conflict of interest to declare.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by Open Project of Tianjin Key Laboratory of Retinal Functions and Diseases (2023tjswmm002), Tianjin Science and Technology Bureau (21JCZDJC01010), and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-037A).\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThis study has not been presented previously.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShih KC, Lam KS, Tong L. 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Contact lens \u0026amp; anterior eye : the journal of the British Contact Lens Association 2023; 46(4):101865.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dry eye, Type 2 diabetes mellitus, Glycemic control, Prevalence","lastPublishedDoi":"10.21203/rs.3.rs-6259419/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6259419/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo investigate the impact of glycemic control and duration of diabetes on clinical manifestation of dry eye in middle-aged and elderly type 2 diabetic population of Tianjin, Northern China.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eParticipants aged over 50 years with type 2 diabetes mellitus (T2DM) were enrolled from December 2019 to August 2022. Systemic and ophthalmic examinations were performed, and diabetic status was screened. Diabetic participants were grouped according to HbA1c levels (HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7.8% and HbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7.8%). In addition, participants were divided into 3 groups according to duration of diabetes (\u0026lt;\u0026thinsp;10 years, 10\u0026ndash;19 years, \u0026ge;\u0026thinsp;20 years). Regression analyses assessed the potential risk factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e1743 participants were included with a mean age of 64.10\u0026thinsp;\u0026plusmn;\u0026thinsp;6.70 years old. 433 (24.84%) was diagnosed with dry eye disease (DED) and 1059 (60.76%) had asymptomatic DED. Women were more likely to have DED than men (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). LLT (P\u0026thinsp;=\u0026thinsp;0.020) in two HbA1c groups had statistical difference. Among different durations of diabetes, CFS (P\u0026thinsp;=\u0026thinsp;0.012), MES (P\u0026thinsp;=\u0026thinsp;0.001) and MQS (P\u0026thinsp;=\u0026thinsp;0.045) were significantly significant. There was a statistically significant association between the history of high blood pressure (HBP) and DED (P\u0026thinsp;=\u0026thinsp;0.042). Meanwhile, people with moderate insomnia had a statistically significant difference in the occurrence of dry eye (P\u0026thinsp;=\u0026thinsp;0.049). Mild (P\u0026thinsp;=\u0026thinsp;0.003) and moderate (P\u0026thinsp;=\u0026thinsp;0.014) anxious populations were more prone to DED.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn the T2DM population, women had a larger proportion of DED than men. The meibomian gland's morphology and function degraded over time in the diabetes. Diabetics with anxiety and sleep deprivation were more likely to have dry eyes.\u003c/p\u003e","manuscriptTitle":"The impact of glycemic control and duration of diabetes on clinical manifestation of ocular surface in middle-aged and elderly type 2 diabetic population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-30 12:13:14","doi":"10.21203/rs.3.rs-6259419/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"663565e8-ef9d-4c75-a330-6f2d2fbc53d9","owner":[],"postedDate":"April 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46521504,"name":"Health sciences/Health care/Public health/Epidemiology"},{"id":46521505,"name":"Health sciences/Diseases/Eye diseases/Eye abnormalities"}],"tags":[],"updatedAt":"2025-08-07T09:56:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-30 12:13:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6259419","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6259419","identity":"rs-6259419","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}