Differential effect of obesity on the incidence of retinal vein occlusion with and without diabetes: a Korean nationwide cohort study

www.nature.com/scientificreports OPEN Differential effect of obesity on the incidence of retinal vein occlusion with and without diabetes: a Korean nationwide cohort study Dong Won Paik1, Kyungdo Han2, Se Woong Kang1, Don‑Il Ham1, Sang Jin Kim1, Tae‑Young Chung1,4* & Dong Hui Lim1,3,4* We aimed to evaluate the association between obesity and the incidence of retinal vein occlusion (RVO) with and without diabetes mellitus (DM).This is a retrospective cohort study using Korean National Health Insurance System data. The participants were 23,061,531 adults older than 20 years who received a health examination at least once between 2009 and 2012, and all patients were observed for RVO development until 2015. We used a multivariate adjusted Cox regression analysis to evaluate the association between RVO and body mass index (BMI) with and without DM. The analysis were evaluated via a hazard ratio (HR) and 95% confidence interval (CI). The age-, sex-, and multivariable-adjusted HRs for RVO were stratified by BMI. This population-based study revealed evidence that obesity has a different effect on the incidence of RVO in the presence and absence of DM.In people with DM, a lower BMI was associated with an increased risk of RVO, and a higher BMI was associated with a lower risk for RVO. In people without DM, the correlation was reversed: a lower BMI was associated with a lower risk for RVO and vice versa. Retinal vein occlusions (RVOs) are a various group of disorders that all involve impaired venous return from the retinal circulation, sudden onset, and the risk of visual morbidity1. RVOs can be classified as central retinal vein occlusions (CRVOs), branch retinal vein occlusions, and hemi-retinal vein occlusions, depending on the site of the obstruction. RVOs are the second most common cause of retinal vascular disease and retinal vascular-related blindness, after diabetic retinopathy2. Patients with an RVO are at risk of vision loss from the complications of the interrupted blood flow, including vitreous hemorrhage, optic neuropathy, macular ischemia, macular edema, or even tractional retinal detachment. Additionally, RVOs often follow or are related to cardiovascular disease such as acute myocardial infarction and stroke. According to a previously published report, patients with incident RVO have an increased risk of stroke just after the RVO event3. RVO has many well-known systemic and ophthalmic risk factors. Typical atherosclerosis risk factors are commonly associated with all types of RVO, but vein occlusions can also be secondary to other processes such as compression, inflammation, or vasospasm4,5. Systemic diseases such as diabetes mellitus (DM), hyperlipidemia (HLD), and hypertension (HTN) are also strongly related to the progression of RVO6. Data from previous studies suggest that 5% of RVO is related to DM, 20% to HLD, and 48% to H TN7. Smoking has also been related 8 to RVO . The Diabetes Control and Complications Study and Blue Mountains Study also reported that DM, arteriosclerosis, HLD, and HTN are risk factors for RVO d evelopment9. 1 Department of Ophthalmology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea. 2Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea. 3Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea. 4These authors contributed equally: Tae-Young Chung and Dong Hui Lim. *email: ; Scientific Reports | (2020) 10:10512 | https://doi.org/10.1038/s41598-020-67375-x 1 Vol.:(0123456789) www.nature.com/scientificreports/ DM is thus a major risk factor for RVO, and it is expected to affect 592 million people in 2035. Asia already contains many people with DM, and DM incidence is increasing at a much faster rate in Asia than in Western countries10. Although obesity is a well-known risk factor for DM and has been suggested as a risk factor for RVO as well, the association of DM and body mass index (BMI) with RVO in previous studies has not been c onsistent11. Moreover, Asians have been reported to have different associations among the percentage of body fat, BMI, and systemic health risks such as cardiovascular disease compared with Europeans and North Americans. In previous studies, body fat percentage (BF %) and certain risk factors have been reported to be elevated at low BMI values12,13. Furthermore, BMI could affect the development of diabetic retinopathy (DR) differently in Western and Asian p opulations14. Whereas in Western populations higher BMI correlated with the incidence of DR, in Asian populations, lower BMI was correlated with DR13,14. As far as we know, the association between baseline BMI with and without DM and the following risk of RVO has not yet been clarified or studied on a large scale. Therefore, we inspected the relationship between BMI with and without DM and future RVO occurrence using nationwide health insurance claims data to determine whether the effect of obesity on RVO incidence varies with the presence of DM. Our underlying hypothesis is that in a Korean population, the incidence of RVO could correlate with lower BMI in DM patients, similar to the previous results showing an inverse association between BMI and DR incidence in Asian p opulations15. Results Baseline characteristics according to BMI and metabolic health status. The baseline characteristics of the study population are presented in Table 1. The average follow-up period was 5.5 years. Participants without DM (NON DM and IFG) are compared to those with DM (NEW DM and MED DM) under the BMI categories of obese (≥ 25 kg/m2) and non-obese (< 25 kg/m2). The total sample numbers were 20,931,217 without DM and 2,130,314 with DM. Compared with those without DM, those with DM were older, more likely to be men, had higher BMI, glucose, and systolic and diastolic BP, and lower HDL cholesterol, and a greater prevalence of HTN and dyslipidemia. Risk of RVO occurrence. Table 2 shows the relationships between baseline BMI and RVO occurrence depending on DM and the associations between baseline WC and RVO incidence. In Model 1, RVO incidence was adjusted for age and sex, and Model 2 was adjusted for age, sex, smoking status, alcohol consumption, exercise, history of hypertension, dyslipidemia, and income status. And in Model 3, eGFR (estimated glomerular filtration rate) was adjusted in addition to model 2. Among the participants without DM, the incidence of RVO was significantly higher in obese and overweight subjects than in subjects with BMI < 23 kg/m2. On the contrary, among participants with DM, the incidence of RVO in overweight and obese subjects was significantly lower than in subjects with BMI < 23 kg/m2. This result was similar for the WC groups: among participants without DM, the incidence of RVO became significantly higher as the WC increased compared wi (...truncated)