key: cord-0954997-1am7fc72 authors: He, Xiaojie; Dai, Feifei; Zhang, Xi; Pan, Jiandong title: The neutrophil percentage‐to‐albumin ratio is related to the occurrence of diabetic retinopathy date: 2022-03-13 journal: J Clin Lab Anal DOI: 10.1002/jcla.24334 sha: 4b4ad8953e4be51b05ee87476e5032face47ffae doc_id: 954997 cord_uid: 1am7fc72 BACKGROUND: Among patients with diabetic retinopathy (DR), no proof was available to confirm the prognostic significance of the neutrophil percentage‐to‐albumin ratio (NPAR). We hypothesized that NPAR plays a role in the incidence of DR in diabetic patients. METHODS: We extracted all diabetes mellitus (DM) data from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2018, NPAR was expressed as neutrophil percentage/albumin. Multivariable logistic regression and generalized additive model were utilized for the purpose of examining the correction between NPAR levels and DR. Subgroup analysis of the associations between NPAR and DR was carried out to investigate if the impact of the NPAR varied among different subgroups. RESULTS: An aggregate of 5850 eligible participants were included in the present research. The relationship between NPAR levels and DR was positive linear. In the multivariate analysis, following the adjustment for confounders (gender, white blood cell, age, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, body mass index, iron, glucose, basophils percent, total bilirubin, creatinine, and chloride), higher NPAR was an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00–1.39; 1.24, 1.04–1.48). For the purpose of sensitivity analysis, we found a trend of consistency (p for trend: 0.0190). The results of the subgroup analysis revealed that NPAR did not exert any statistically significant interactions with any of the other DR risk variables. CONCLUSIONS: Elevated NPAR is associated with an elevated risk of occurrence of DR in diabetic patients. Globally, diabetes mellitus (DM) afflicted approximately 415 million individuals in 2015, with the value anticipated to climb to 642 million by the year 2040. 1 With the growing incidence of diabetes and the increase in the population with diabetes having longer life expectancies, the number of people experiencing visual impairment and diabetic retinopathy (DR) as a result of this disease is growing on a global scale. 2 DR has been identified as the major contributor to visual impairment among the working-age populace in the Western world. 3 Patients with diabetes or DR experience more functional physiological difficulties than those without diabetes, especially profound among those with severe DR. 4 Multiple studies have shown that diabetic control in patients with type 2 DM is associated with serum vitamin D levels, 5 uric acid to high-density lipoprotein (HDL) cholesterol ratio, 6 and omentin levels. 7 And some of its complications are associated with inflammation, such as platelet-to-lymphocyte ratio, 8 neuregulin-4, 9 and C-reactive protein to serum albumin Ratio. 10 DR is caused by a variety of pathologic variables that can result in visual impairment, including proliferative vitreoretinopathy, intraocular neovascularization, as well as diabetic macular edema. 11, 12 Microangiopathy and inflammation jointly perform an integral function in the pathogenic mechanism of DR. 13 The neutrophil percentage-to-albumin ratio (NPAR) is a viable biomarker for systemic infection and inflammation that has recently been discovered. According to the findings of several research reports, NPAR might be utilized as a prognostic factor for individuals with acute kidney damage, cardiogenic shock, severe sepsis, and cancer. [14] [15] [16] [17] It is generally recognized that neutrophils perform critical functions in the cellular innate immunity. Prior research has indicated that elevated neutrophil expression levels in the early stages of sepsis were associated with greater severity of the condition. 18, 19 Moreover, neutrophil-derived inflammatory markers have been studied in and found to be associated with various inflammatory conditions such as inflammatory bowel disease, 20 irritable bowel disease, 21 diabetes mellitus, 22 atrial fibrillation, 23 thyroiditis, 24 and SARS-Cov-2 infection. 25 Albumin is a medium-sized protein that constitutes the majority of the proteins found in human plasma. Albumin plays an essential role in a wide range of physiological processes. Moreover, it performs a wide range of functions in the body, such as acting as a significant buffer, antidote, immunomodulator, extracellular antioxidant, and transporter in the plasma. 26, 27 The correlation between NPAR and DR, nevertheless, has received little attention to date. As a result, the purpose of the present research was to examine the function of NPAR in the prediction of DR in diabetic individuals. The National Health and Nutrition Examination Survey (NHANES) database provides a clustered, stratified, multistage, cross-sectional probability sample comprising of a population of non-institutionalized US civilians that is performed by the National Center for Health Statistics (NCHS), which is a branch of the Center for Disease Control and Prevention . The NHANES III survey was performed between 1988 and 1994, and the continuing NHANES survey was carried out between 1999 and 2020, with data published in 2-year cycles. The NCHS institutional review board granted its approval for the methodology for conducting the NHANES and informed written consent was obtained from all subjects. The Ethics Review Board of the National Center for Health Statistics (NCHS ERB) granted its approval for the NHANES (NCHS IRB/ERB protocols #98-12, #2005-06, #2011-17, #2018-01). Respondents in the NHANES undergo a health assessment at mobile examination centers after an in-home interview. Participants' physiological and clinical conditions are evaluated, followed by laboratory examinations. We extracted all DM data from NHANES 1999 to 2018. The exclusion criteria were as follows: participants under 18 years of age, no albumin or neutrophil percentage measured, and having more than 5% missing data. The extracted data included age, gender, marital status, neutrophil percentage, albumin, mean cell hemoglobin, total cholesterol, eosinophil percent, high-density lipoprotein, body mass index (BMI), glucose, triglycerides, hematocrit, white blood cell (WBC), diastolic blood pressure (DBP), monocyte percent, glutamyl transpeptidase, systolic blood pressure (SBP), basophils percent, hemoglobin, lymphocyte percent, mean cell volume, red cell distribution width (RDW), platelet, red blood cell, alkaline phosphatase, blood urea nitrogen, globulin, total bilirubin, bicarbonate, uric acid, aspartate aminotransferase (AST), creatinine, sodium, potassium, chloride, phosphorus, total calcium, iron, alanine aminotransferase (ALT), hypertension, and diabetic retinopathy. NPAR was expressed as neutrophil percentage/albumin. Distribution normality was initially tested through the Kolmogorov-Smirnov test. Continuous variables were presented as mean ± SD or interquartile range (IQR) and medians. Categorical data were presented as percentages or frequencies. For the purpose of investigating whether there were any significant differences among various groups, the Kruskal-Wallis H, one-way ANOVA, and Chi-square tests were utilized. The linear correlation between NPAR and the incidence of DR was established with the aid of a generalized additive model. Moreover, a multivariate logistic regression model was conducted to analyze the correlation by identifying possible confounding variables; these findings were presented as odds ratios (ORs) with 95% confidence intervals (CIs). We integrated the prospective confounding parameters on the basis of epidemiologic and biologic backgrounds and selected only those with a shift in effect estimate of greater than 10% for the purpose of constructing an adjusted model. 28 Two multivariate models were constructed based on NPAR group inclusion according to tertiles. The initial tertile was employed as a point of reference throughout the study. The gender and age of the covariates were subjected to adjustment in model I. In model II, we subsequently adjusted for gender, age, white blood cell, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, basophils percent, body mass index, iron, glucose, total bilirubin, creatinine, and chloride. Subgroup analysis of the correlation between NPAR and DR was carried out for the purpose of determining if the impact of the NPAR varied among subgroups. All probabilities were two-sided and statistical significance was fixed at p < .05. All analyses of statistical data were carried out using the R software (version: 4.00). We identified 5850 diabetic individuals who satisfied our participation requirements and conducted a study on them. The patients were classified into tertiles based on their NPAR scores. Totally, 2829 women, as well as 3021 men, fulfilled the criteria for participation, and 1301 patients underwent a diagnosis of DR (22.2%). Table 1 summarizes the baseline characteristics. Patients who had an elevated NPAR (NPAR ≥ 15.6 ml/g) were more likely to be elderly with a high incidence of DR. Participants with lower NPAR (NPAR < 13.3 ml/g) had higher values of DBP, mean cell hemoglobin, total cholesterol, mean cell volume, hematocrit, hemoglobin, red blood cell, basophil percent, eosinophil percent, monocyte percent, triglycerides, high-density lipoprotein, lymphocyte percent, ALT, AST, total bilirubin, phosphorus, total calcium, and iron. The relationship between NPAR levels and DR was positive linear ( Figure 1 ). The correlation between NPAR and the prevalence of DR was determined with a logistic multivariate regression model ( Table 2 ). The lower NPAR was used as a reference. In model I, after correcting gender and age, a greater NPAR was related to an elevated risk of DR. In model II, after accounting for confounding variables (gender, age, white blood cell, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, basophils percent, body mass index, iron, glucose, total bilirubin, creatinine, and chloride), higher NPAR remained an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00-1.39; 1.24, 1.04-1.48). After conducting sensitivity analysis, we found a trend of consistency (P for trend: 0.0190). Table 3 shows the results of a subgroup analysis of the correlation between NPAR and the risk of DR, indicating that there was no interplay in these strata (p = .0563-0.9447). Moreover, no statistically significant interactions were discovered between NPAR and any of the other risk variables for DR. A positive linear correlation was observed between NPAR and the risk of incidence of DR. Elevated NPAR levels were found to be correlated with an elevated incidence of DR in the fully adjusted model among diabetic patients. Furthermore, no statistically significant interactions between NPAR and any of the other potential risk factors were observed, indicating that no additional factors had been discovered that could modify the correlation between NPAR and the risk of incidence of DR. As far as we know, this is the first study to highlight the significant correlation between NPAR and DR in diabetic patients. NPAR was discovered to be a new indicator for systemic infection and inflammation in humans. 14, 29 The elevated NPAR levels are According to the aforementioned results, we hypothesized that NPAR, the blending of albumin and neutrophils, has a high prognostic significance in the progression of DR. NPAR is simplistic, inexpensive, and rapid, which makes it a potential indicator that may be used even in undeveloped medical areas. This In diabetic individuals, we revealed that elevated NPAR is correlated with a higher risk of suffering from DR. Nevertheless, these findings need to be validated by prospective multicenter studies. The authors report no conflicts of interest for this work. XJH and FFD designed the study and collected, analyzed and interpreted the data. XZ collected and analyzed data and drafted the manuscript. JDP designed and supervised the study, obtained funding, and drafted the manuscript. All authors read and approved the final manuscript. The protocols for conduct of NHANES were approved by the NCHS institutional review board and all participants provided informed consent. The data used in the present research were obtained from publicly accessible sources. These data, according to the authors, could be accessible at the following URL: https://www.cdc.gov/nchs/nhane s/. 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