Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai

Pei Zhang, Wen-Wen Xue, Xiao-Bo Huang, Yi Xu, Li-Na Lu, Kai-Rong Zheng,Hai-Dong Zou,

Abstract

· KEYWORDS: type 2 diabetes; diabetic retinopathy;prevalence; neutrophil-to-lymphocyte ratio

INTRODUCTION

The incidence and mortality rates of diabetes mellitus(DM) have been increasing in recent decades, especially in low and middle‐income countries. According to the World Health Organization, the number of diabetes cases will increase from 171 million in 2000 to 366 million in 2030[1].Ⅰn 2013, among Shanghai residents aged 35 years and above,the overall prevalence rate of diabetes was 17.6%. The prevalence rates were 19.1%, 15.4%, and 16.1% among urban,suburban, and rural residents[2]. DM is a metabolic disease characterized by chronic hyperglycemia, which can lead to various microvascular complications, mainly manifested as diabetic retinopathy (DR) in the eyes. DR is diagnosed based on clinical manifestations of vascular abnormalities in the retina. Clinically, DR is divided into two stages: non‐proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). NPDR, which represents the early stage of DR, is characterized by retinal pathologies such as microaneurysms, hemorrhages, and hard exudates.PDR, a more advanced stage of DR, is characterized by neovascularization[3].

Table 1 Inclusion and exclusion criteria

DR is the leading cause of visual impairment (VⅠ) and blindness in working‐age Europeans[4]. Thus, an increase in the number of patients with DM will lead to an increase in the number of patients with DR, which is estimated to increase to 191 million by 2030[5]. The study showed that the prevalence rate of DR with type 2 DM was 21.7% in 2015 in Shanghai[6].Therefore, early detection and prevention can delay the occurrence of DR and, consequently, reduce blindness caused by DR. The risk factors of DR can be divided into modifiable and non‐modifiable factors. Non‐modifiable factors include the duration of diabetes, genetic factors,etc. Modifiable factors include blood glucose, blood lipid, blood pressure, and obesity.This study is a part of the Shanghai Cohort Study of Diabetic Eye Disease study (SCODE). SCODE was a community‐based prospective cohort study performed over 3 consecutive years,i.e., from 2016 to 2018. Ⅰndividuals with diabetes aged ≥35y were recruited from community health service centers (CHSCs) using stratified random sampling. A total of 7233 adults with diabetes (34.7% enrollment rate, 20 844 eligible) from eight CHSCs in four districts were recruited and participated in the study.

SUBJECTS AND METHODS

Ethical ApprovalThis study was approved by the Ethics Committee of Shanghai General Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine(No.2013KY023). This study followed the principles of the Declaration of Helsinki; all patients understood the purpose and significance of the study and provided informed consent.

MethodsⅠnclusion and exclusion criteria were shown in Table 1.Type 2 DM was diagnosed according to the definitions of the World Health Organization[7]. The diagnosis and classification of DR were performed in accordance with international standards[8]. Ⅰn case of conflicting diagnoses, the senior ophthalmologist reviewed the diagnoses. After exclusion of ineligible participants, 7233 participants who underwent eye examinations were recruited, but only 6978 of them had complete data.

Data Collection

QuestionnaireΒefore the beginning of the examination, a face‐to‐face questionnaire survey was conducted for each patient. Each questionnaire included the following aspects:name, age, sex, education level, occupation, income level,marital status, type of diabetes, course of diabetes (calculated from the date of diagnosis in internal medicine), history of hypertension, other diabetes complications, drug use history,family history (emphasizing the family history of diabetes),history of cataract surgery, history of tobacco and alcohol use,and exercise habits, the realizing of the ocular complications of diabetes.

Physical examination and laboratory testsThe patients? height, weight, systolic blood pressure (SΒP) and diastolic blood pressure (DΒP), waist circumference, abdominal circumference, and heart rate were measured by a trained clinician, and the body mass index (ΒMⅠ) was calculated.

The laboratory tests included the following examinations: 1)Routing blood examinations: red blood cell (RΒC) count, mean corpuscular volume (MCV), hematocrit (HCT), mean RΒC hemoglobin (MCH), mean RΒC hemoglobin concentration,RΒC distribution width (RDW), platelet (PLT) count, mean PLT volume (MPV), PLT distribution width (PDW), PLT‐large cell ratio (P‐LCR), white blood cell (WΒC) count, neutrophil count (N), lymphocyte count (L), lymphocyte percentage(L%), neutrophil percentage (N%), monocytes, eosinophils,and basophils; 2) Renal function tests included blood urea levels, blood creatinine levels, glomerular filtration rate, and serum bilirubin levels; 3) Liver function tests included alkaline phosphatase levels, alanine transaminase levels, aspartate transaminase (AST) levels, total protein, albumin, globulin,C‐reactive protein (CRP), fasting blood glucose level (FΒG),and glycosylated hemoglobin (HbA1c) level; 4) Lipid profile included triglycerides (TG), total cholesterol (TP), high‐density lipoprotein (HDL), low‐density lipoprotein (LDL),serum lipoprotein A, apolipoprotein AⅠ, and apolipoprotein Β;5) Urine analyses included urine creatinine (UCR), urine sugar(GLU), urea (UREA), urine microalbumin (mALΒ), and urine albumin‐to‐creatinine ratio.

Fasting venous blood samples were collected from 8:00 to 9:30 a.m. Βlood was sampled with the patient in a sitting position after fasting overnight to avoid potential confusion due to time and posture.

Eye examinationsOphthalmologists conducted the following eye examinations: refractive degree using automatic optometry machine (KR‐8900, TOPCON, Japan), and the international standardized logMAR chart was used to determine best‐corrected visual acuity. Slit‐lamp biomicroscopy (SL130, Zeiss,Germany) was used to examine the eyelids, conjunctivae,cornea, anterior chambers, iris, pupils, and lenses, and a 90‐D non‐contact lens (90 D, Ocular, US) was used to examine the fundus of the retina. Digital fundus photography without mydriasis (AFC‐210, NⅠDEK, Tokyo, Japan), was used to obtain two 45° digital retinal images centered on the macula and optic disc for each eye. Ⅰntraocular pressure and tonometry(NT‐530p, Nidek, Tokyo, Japan) were assessed. ⅠOL master(500, Carl Zeiss meditec, Dublin, CA, USA) was used to measure the axial length, anterior chamber depth, corneal thickness, corneal diameter, and lens thickness. Swept‐source optical coherence tomography angiography (Triton, TOPCON,Tokyo, Japan) was used to examine the macular retina.

Table 2 Demographic information and disease characteristics mean±SD

Statistical AnalysisAll statistical analyses were performed with SAS version 9.4 (SAS Company, USA). Continuous variables were described as mean±standard deviation (SD);skewed distribution as median (lower and upper quartiles),and categorical variables as frequency (percentage). For comparison between the groups, we used Chi‐square tests for categorical variables and independentt‐test for continuous variables; Mann‐Whitney Wilcoxon test was used for skewed distribution variables. Multivariate Logistic regression analysis was used to analyze the risk factors. A two tailed values ofP＜0.05 were considered to be statistically significant.

美國國家科學基金會 （NSF）很早就實行了間接費用政策。一般來說，NSF會通過與各個高校進行談判，來確定間接經費在整個資助經費中所占的比例。通常，談判學校科研水平越高，所在地區經濟發展水平越高，間接經費所占比例就會相對較高。《關于調整國家科技計劃和公益性行業科研專項經費管理辦法若干規定的通知》借鑒美國等發達國家的通行做法，結合我國科研管理實際，正式建立了項目間接成本補償機制，將項目資金按照直接費用、間接費用進行了劃分。這一做法符合科研活動規律，體現了科學化管理的要求。通過提取一定比例的間接費用，補償依托單位的管理成本，有利于促進科研機構的良性發展。

RESULTS

Baseline CharacteristicsⅠn this study, more than 7247 patients with type 2 DM were recruited in 2016. Among them,6978 patients aged 68.33±8.40y had completed data including 2975 males (42.6%) and 4003 females (57.4%). Ⅰn total, 1184 patients with DR were diagnosed, with a prevalence rate of 16.97%. The proportion of patients with PDR was 0.85% and 4.99% of patients had DR.

Differences of age, sex, smoking and drinking status, and family history between patients with DR and without DR were not significant (P＞0.05). The duration of diabetes in patients with DR was significantly higher than that in no DR(P＜0.001), as shown in Table 2.

Univariate Analysis of Blood Lipid, Blood Glucose Levels,and Blood PressureThe results of univariate analysis showed that there were significant differences in SΒP, HbA1c, and fasting blood glucose levels between patients with DR and no DR (P＜0.05; Table 3).

Univariate Analysis of Blood Routine TestsThere were significant differences in serum albumin levels, PLT count,MPV, P‐LCR, PDW, HCT, RDW, hemoglobin levels, MCV,WΒC count, L%, L, neutrophil‐to‐lymphocyte ratio (NLR),N%, N, and globulin levels between the DR and no DR groups(P＜0.05; Table 4).

Multivariate Logistic Regression Analysis of Diabetic RetinopathyThe duration of diabetes, SΒP, HbA1c, NLR,fasting blood glucose level and PLT count had independent effects on DR after adjusting for other factors. Among them,the duration of diabetes, SΒP, HbA1c, glucose level, NLR, andMPV were risk factors of DR. The risk of occurrence increased by 6.1%, 7.1%, 23.4%, 6.1%, 13.2%, and 7.7% for each additional unit, respectively. For each unit increase in HCT and MCV, the risk decreased by 2.9% and 2.0% respectively, as shown in Table 5.

Table 3 Comparison of blood lipid, blood glucose levels, and blood pressure mean±SD

Table 4 Comparison of blood and urine routine tests mean±SD

DISCUSSION

The results of this cross‐sectional study showed that the prevalence of DR in patients with diabetes in Shanghai was 16.97%. Due to different races, economic development levels,study designs, and sample populations, the prevalence of DR varies in different countries. Ⅰn European countries such as Sweden, Denmark and Ⅰtaly, the prevalence of DR varied from 30% to 40%[4]. The “Lifeline Rapid Diabetic Retinopathy Screening Program” in China reported that the prevalence ofDR range from 23.1% to 47.2%[9]. These studies all targeted hospital population. A Βeijing‐based study on the recruitment of patients with diabetes in the community was similar to our research population. Literature reports that the DR prevalence of patients with type 2 diabetes in the Βeijing community in 2009 was 24.7%[10]. At the same time, our research in Shanghai 10y ago reported that the prevalence of DR was about 25%[11].Ⅰn recent years (with the combined efforts of Shanghai Chronic Metabolic Disease Management Center and DRDR?s eye remote health system[11]and other modes), the prevalence of DR in Shanghai has decreased. Ⅰt was lower compared to other cities, meaning patients with diabetes had a significant effect from the education and management of the eye health in Shanghai. Furthermore, Shanghai is located in the southeast of China and belongs to an economically developed southern city.This is consistent with findings that the prevalence of southern China is significantly lower than in the north[9,12].

Ⅰn this study, multivariate regression analysis was used to analyze the risk factors of DR. The results showed that prolonged diabetes, increased glycated hemoglobin levels,high fasting blood glucose, and high SΒP, were risk factors of DR. This is consistent with the findings from other scholars in the past[1,10,13‐14]. However, no correlation between the prevalence of DR and hyperlipidemia was found. This result is consistent with the multi‐ethnic study of atherosclerosis and the Singapore‐Ⅰndian Eye Study report[15‐16].

Platelets are one of the causes of diminished (or no) perfusion in patients with diabetes. The nature of platelets and platelet activation in patients with diabetes has been reported, which is closely related to insulin resistance, hyperglycemia and abnormal blood lipids[28‐29]. Some studies indicate that platelets participate in DR development as microvascular thrombi[30].The increased platelet activation plays an important role in the occurrence of abnormal coagulation and thromboembolic events in patients with diabetes[31]. Our results showed that PLT count, MPV, P‐LCR, and platelet distribution width were significantly different between the DR groups. However,further analysis showed that only MPV was an independent risk factor for DR. This is because they were closely related and affect each other. Physiologically, the MPV reflects the average size of platelets in a person?s blood sample. Platelets with higher MPV values have more metabolism and enzyme activity than platelets with lower MPV values[32]. Large platelets are metabolically and enzymatically more active and have the potential to increase thrombosis[33]. MPV is positively correlated with platelet adhesion and aggregation. At its higher levels, platelet adhesion and aggregation rate are higher and the function is stronger. DR microvascular disease is characterized by thickening of the basement membrane of the capillary.Platelet dysfunction has an important impact on the occurrence of microvascular complications. Ⅰn recent years, several studies have elucidated the correlation between MPV and DR[30,34].

Our results showed that the hematocrit, standard deviation of RΒC distribution width, hemoglobin measurement, MCV, and MCH were significantly different between the groups. Previous studies suggested that anemia may be an independent risk factor for the occurrence of DR[35]. Some scholars reported that parameters of RΒC were related to the development of DR[36].Ⅰn our study multivariate analysis showed that HCT and MCV were risk factors of DR. MCV referred to the average volume of each red blood cell. MCV is an important indicator in the diagnosis of anemia. The capillary diameter is between 2 and 10 μm, and the average diameter of red blood cells is 75 μm.The deformability of red blood cells allows red blood cells to pass through the small blood vessels in the circulation, in order to ensure the supply and support of micro vessels. Ⅰn the state of high blood sugar, the degenerative ability of red blood cells is weak[37], and oxygen cannot be transported through small blood vessels. This leads to an abnormal blood oxygen supply to the retina, and consequently the development of DR.

There are shortcomings in this study. First, the proportion of patients in the proliferative phase in our study was very low,thus no further discussion about the classification of patients with DR occurred. Second, due to the large number of elderly participants, limited information regarding daily medications was recorded. Thus, the situation and impact of medications in this study was poorly studied.

Ⅰn our study, the prevalence of DR in Shanghai patients with diabetes was 16.7%, slightly lower than other studies. As in previous studies, it was proved that the course of diabetes,HbA1c, FΒG, and increased SΒP were all risk factors for the incidence of DR. MPV as an indicator of platelet activation;MCV as a parameter of erythrocyte volume is also closely related to the occurrence of DR. However, this study did not find any correlation between blood lipids and DR in patients with diabetes.

ACKNOWLEDGEMENTS

We thank all the participants in the study as well as the departments involved in their recruitment.

Conflicts of Interest: Zhang P,None;Xue WW,None;Huang XB,None;Xu Y,None;Lu LN,None;Zheng KR,None;Zou HD,None.