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3Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital ... Methods: The Handan Eye Study is a population-based cross-sectional study surveyed ...... Chew EY, Klein ML, Ferris FL III, Remaley.
Acta Ophthalmologica 2011

Risk factors for diabetic retinopathy in a rural Chinese population with type 2 diabetes: the Handan Eye Study Feng Hua Wang,1 Yuan Bo Liang,1,2 Xiao Yan Peng,1 Jie Jin Wang,3,4 Feng Zhang,1 Wen Bin Wei,1 Lan Ping Sun,2 David S. Friedman,5,6 Ning Li Wang,1 Tien Yin Wong,3,7 and the Handan Eye Study Group1 1

Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Science Key Lab, Beijing, China 2 Handan Eye Hospital, Hebei Province, China 3 Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia 4 Centre for Vision Research, University of Sydney, Sydney, Australia 5 Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA 6 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA 7 Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

ABSTRACT. Purpose: To describe risk factors associated with diabetic retinopathy (DR) in a popu-

Introduction

lation-based sample of rural Chinese with type 2 diabetes. Methods: The Handan Eye Study is a population-based cross-sectional study surveyed 6830 Chinese people aged 30+ years from 13 randomly selected villages in 2006–2007. All participants underwent a standardized interview and extensive examinations including ophthalmologic and systemic conditions. Diabetic retinopathy was graded from fundus photographs according to the modified Early Treatment Diabetic Retinopathy Study classification system. Logistic regression models were used to assess risk factors associated with DR. Results: Of 7577 eligible persons, 6830 (90.4%) participated, of which 5597 (81.9%) had fasting plasma glucose (FPG) data. There were 387 (6.9%) participants with diabetes, and 368 (95.1%) had gradable fundus photographs. The age-standardized prevalence of DR was 43.1%. In multivariable-adjusted logistic regression models for all diabetic participants, independent risk factors for DR were longer duration of diabetes (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.94, 4.85, per 5 years of duration), higher FPG levels (OR 1.17; 95% CI: 1.08, 1.27, per mmol/l increase) and higher systolic blood pressure (OR 1.22; 95% CI: 1.08, 1.37, per 10 mmHg increase). For newly diagnosed diabetes, the only significant factor of DR was higher FPG levels (OR 1.17; 95% CI: 1.05, 1.29, per mmol/l increase). Conclusions: In rural Chinese persons with diabetes, longer diabetes duration, hyperglycaemia and elevated blood pressure are risk factors for DR. These findings underscore the importance of controlling classic risk factors for DR in developing countries, where diabetes prevalence is increasing.

Diabetic retinopathy (DR) is the leading cause of visual impairment among working adults in the Western world (Fong et al. 2004; Kempen et al. 2004). Epidemiological studies, largely conducted in white populations, have shown that duration of diabetes, hyperglycaemia and hypertension are the major independent risk factors for DR (Klein et al. 1984, 1992; Stolk et al. 1995; Mitchell et al. 1998; McKay et al. 2000; West et al. 2001; van Leiden et al. 2002, 2003; Tapp et al. 2003; Varma et al. 2004, 2007; Wong et al. 2006a,b). Associations with hyperlipidemia (Klein et al. 1991; Chew et al. 1996; van Leiden et al. 2002; Rema et al. 2006), obesity (Klein et al. 1997; van Leiden et al. 2002; Wong et al. 2006a,b) and other risk factors (Klein et al. 2002a,b) have been less consistently documented. In the past few decades, the prevalence of diabetes mellitus (DM) in China has increased substantially (Chan et al. 2009). However, there are few population-based data on risk factors for DR in Chinese people,

Key words: diabetes mellitus – diabetic retinopathy – epidemiology – population based study

Acta Ophthalmol. 2011: 89: e336–e343 ª 2011 The Authors Acta Ophthalmologica ª 2011 Acta Ophthalmologica Scandinavica Foundation

doi: 10.1111/j.1755-3768.2010.02062.x

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Acta Ophthalmologica 2011

particularly in rural communities, which form 60% of China’s population (Wong et al. 2006a,b; Wang et al. 2009). We conducted the Handan Eye Study (HES) with an aim to determine the epidemiology of major eye diseases in rural China. We recently reported a prevalence of DR of over 40% in our study. Notably, we found a high ratio of undiagnosed DM (64%) and also a high proportion with DR among both the newly diagnosed cases and the known diagnosed diabetes (KDM) (Wang et al. 2009). Whether the traditional DR risk factors found in white populations are similar in rural Chinese populations with diabetes is unknown. The purpose of this study is to assess risk factors associated with the DR in a rural Chinese sample aged 30+ years who had type 2 diabetes.

Methods Study population

The HES is a population-based, crosssectional study of 6830 Chinese adults, aged 30 years and older recruited between October 2006 and October 2007 from 13 randomly selected villages of Yongnian county, Handan city, Hebei province. The study was approved by the Beijing Tongren Hospital Ethical Committee and written informed consent was obtained from all participants. Details of the study design, sampling plan and baseline data are reported elsewhere (Liang et al. 2008, 2009). Briefly, 7557 eligible people confirmed by door-to-door census of the study region were invited to visit Yongnian county hospital for a detailed examination including a standardized interview, a comprehensive eye examination and laboratory investigations for fasting blood samples. Definition of diabetes mellitus and diabetic retinopathy

Diabetes mellitus (DM) was defined as either fasting plasma glucose (FPG) ‡7.0 mmol/l, use of diabetic medication or a physician diagnosis of diabetes. Diabetes was considered to be type 1 if the participant was younger than 30 years when diagnosed with diabetes and was receiving insulin therapy. Otherwise, DM was considered to be

type 2. Type 2 diabetes was diagnosed by a self-reported history of physician diagnosis or receiving medical treatment for diabetes (insulin or oral hypoglycaemic agents), as KDM, or by FPG of 7.0 mmol/l (126 mg ⁄ dl) or higher at examinations, as newly diagnosed diabetes (NDM) subjects. Fundus photographs of field 1 (optic disk centred) and field 2 (macula centred) were taken from both eyes of each participant through dilated pupils using a digital nonmydriatic retinal camera (Canon CRDGi with a 20D SLR back; Canon, Tokyo, Japan) and graded in a masked manner according to the grading protocols used in the MultiEthnic Study of Atherosclerosis (MESA) that was modified from the Early Treatment Diabetic Retinopathy Study (ETDRS) classification system (1991), Wong et al. (2006a), Wong et al. (2006b), Wang et al. (2009). Retinopathy was considered present if any characteristic lesion as defined by the ETDRS severity scale was present: microaneurysms, haemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading and new vessels. The level of retinopathy for each eye was determined, and individual classification was based upon the worst eye. Eyes were graded according to the following criteria: (i) no DR (levels 10 through 13) or (ii) any DR (levels 14 through 80). Diabetic retinopathy was further divided into minimal nonproliferative diabetic retinopathy (NPDR) (levels 14–20), mild-moderate NPDR (levels 31–41) and severe NPDR to proliferative retinopathy (levels 51– 80). Digital images underwent a preliminary and detailed grading for the presence and severity of DR by two graders (WF and SR). Discrepancies between the two graders were adjudicated by a senior ophthalmologist (ZF) whose grade was used as the final one. The unweighted j statistics calculated for inter-grader and intragrader agreement on a randomly selected subset of 100 participants stratified by retinopathy severity level were j = 0.98 and j = 0.91, respectively, indicating excellent agreement.

nation, and laboratory investigations (Liang et al. 2008). The duration of diabetes was calculated as the difference between the year of diagnosis (as reported by the participant) and the year of the HES examination. Those with NDM were assigned a diabetes duration of 0 year, to be consistent with previous studies (Klein et al. 1984; Varma et al. 2007). Awareness of DM was defined as participants’ self-reporting any prior diagnosis of DM made by a health care professional among the population considered as having DM, which is identical to KDM. Treatment of DM was defined as use of a prescription medication diet or exercise intervention for management of high glucose at the time of the interview. Control of DM was defined as having pharmacological treatment of DM and achieving a fasting glucose £7.0 mmol/l. Anthropometric measurements including weight, height and waist measurements were obtained using standardized techniques. The body mass index (BMI) was calculated as weight divided by height squared (kg ⁄ m2) and waist hip ratio (WHR) was the waist circumference divided by the hip circumference. Ankle–brachial index (ABI) was measured with a Colin BP-203RPE II (VP-1000) (Colin, Komaki, Japan). Blood pressure (BP) was taken with the participant seated and after 5 min of rest by using a digital automatic blood pressure monitor (OMRON model Hem-907 automated oscillometric sphygmomanometer; OMRON, Tokyo, Japan) according to a protocol similar to that used in the MESA (Wong et al. 2006a,b). Hypertension was defined if systolic blood pressure (SBP) ‡140 mmHg or diastolic blood pressure (DBP) ‡90 mmHg at examinations or the participant had a previous physician diagnosis (Chobanian et al. 2003). A fasting blood sample was taken and sent to the Handan Central Hospital at the same day to assess levels of FPG, fasting serum total cholesterol, low density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides.

Assessment and definitions of risk factors

Statistical analysis

Participants underwent a standardized interview, systemic and ocular exami-

We constructed logistic regression models to determine the odds ratios

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Table 1. Age- and gender-adjusted associations between risk factors and diabetic retinopathy among participants with all diabetes in the Handan Eye Study. Total diabetes sample (n = 368) Risk factors Demographic factors Age (years) 30–39 40–49 50–59 60–69 ‡ 70 Gender Male Female Medical history Diabetic duration, years Newly diagnosed diabetes