Diabetic retinopathy (DR), remains the most common and serious microvascular complications of diabetes mellitus . The prevalence of DR increases with the number of diabetics, and nearly all persons with type 1 diabetes and more than 60% of those with type 2 have some retinopathy after 20 years [2, 3]. It is also considered to be the leading cause of sight-threatening disease in working-aged people . Factors that are known to influence the development of diabetic retinopathy include modifiable factors, such as blood glucose and blood pressure, smoking, and some non-modifiable factors, such as age, race, and duration of diabetes [5–7].
Zinc is an essential trace element that is obtained from food. It plays an important role in growth and development, immune function, and material metabolism [8–10]. Moreover, zinc has an antioxidant effect, mainly through the following two mechanisms protect tissues from oxidative stress, protect sulfhydryl groups from oxidation, and inhibit the production of reactive oxygen by transition metals [11, 12]. In addition, studies have shown that it can also reduce oxidative stress by inhibiting anti-inflammatory response . Some studies support that zinc can affect glucose homeostasis and improve glycemic control in diabetic patients . Zinc can protect diabetic retinopathy by inhibiting pericytes apoptosis, capillary leakage, and neovascularization, it may be beneficial to prevent diabetic retinopathy .
At present, the research on the beneficial effects of antioxidant nutrients on various disorders caused by oxidative stress and diseases has also received widespread attention. However, there are few studies on the potential effects of dietary antioxidant nutrients on diabetes retinopathy. So this paper focuses on the relationship between dietary zinc intake and diabetic retinopathy in US adults through the National Health and Nutrition Examination Survey database.
1.1 Study Population
The data used in this study were obtained from the NHANES database. NHANES is a cross-sectional survey launched by the National Center for Health Statistics (NCHS) to assess the health and nutritional status of adults and children in the United States. It is released to the public in a two-year cycle. For data users and researchers throughout the world, survey data are available on the internet . The NHANES protocol was approved by the National Center for Health Statistics Ethics Review Board of the US CDC, and all subjects participating in the survey have signed informed consent.
In this study, a total of 59842 individuals participated in the NHANES during 2007 to 2018, of which, 23226 adults aged 40 years and over were identified. In addition, we excluded those who were pregnant (n = 18) and lactating (n = 16). Those who did not complete the dietary review survey (n = 2690) and with an incomplete disease definition questionnaire (n = 16676) were also excluded. Moreover, the individuals with extreme dietary total energy intake (women: <500 or > 5000 kcal/day, men: <500 or > 8000 kcal/day) were further excluded from our study population (n = 32). Finally, 3794 participants (2001 men and 1793 women) were included in the analysis. The detailed process is shown in Fig. 1.
1.2 The Definition of Diabetic Retinopathy
In the main analysis, “diabetes” was defined as the response of "yes" for any of the following questions: “Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes” or “Are you now taking insulin?” or “Are you now taking diabetic pills to lower blood sugar?” Similarly, we classified respondents as having DR if they answered “yes” to the NHANES question, “Has a doctor ever told you that diabetes has affected your eyes or that you had retinopathy?”  .
1.3 Dietary Zinc Intake Assessment
Dietary intake data were assessed by using two 24-hour recall interviews. The first dietary recall interview was collected face-to-face interview between the food interviewer and the participants in the Mobile Examination Center (MEC), and the second dietary recall was collected by telephone and was scheduled 3 to 10 days later. The total dietary intake of zinc was the average intake of two 24-hour dietary review survey data. If participants had not participated in the second survey, the single dietary recall data were used. In addition, the supplements intake of zinc during the past 30 days was also collected, and the average value was taken to represent the daily supplementary intake. Finally, the total zinc intake was calculated by summing the daily dietary and supplementary intake.
The following covariates were included in this study: gender, age, race, educational level, marital status, BMI, annual family income, hypertension, smoking, and total energy intake were obtained from 24-hour dietary recall. We stratified blood glucose control according to HbA1c levels into well-controlled (HbA1c < 7%) and poorly controlled (HbA1c ≥ 7%). Duration of diabetes (< 5 years, 5–10 years, at least 10 years) was calculated from the reported age at screening minus the age of the subject when first told he/she had diabetes.
1.5 Statistical Analysis
All analyses were conducted using SPSS 24.0 and R 3.5.2. According to NHANES analytical guidelines, new special 12-year dietary weights were created by taking one-sixth of the 2-year dietary weights. Kolmogorov-Smirnov normality test was used to verify the normality of continuous variables. Characteristics were described as mean ± standard deviation for normal variables, median (interquartile range) for non-normal variables, and number (percentage) for categorical variables. The differences between continuous and categorical variables were investigated using the independent t-test and the Chi-squared test, respectively.Binary logistic regression analyses were used to explore whether there were associations between dietary zinc intake and DR. We conducted a gender stratified analysis. Model 1: unadjusted. Model 2: adjusted for age. Model 3: adjusted by model 2, race, education, marital status, family income, duration of diabetes, glycemic control, hypertension, smoking, and total energy. In addition, we used a restricted cubic spline (RCS) to further explore the dose-response relationships between dietary zinc intake and DR. To assess the optimal cut-off points of dietary zinc intake, a receiver operating characteristic (ROC) curve analysis was conducted. A two-sided P-value < 0.05 was considered statistically significant.