Shanshan Du

Background: Diabetic retinopathy (DR) is one of the most prevalent microvascular complications of diabetes mellitus and a leading cause of visual impairment worldwide. However, clinically available, minimally invasive, and convenient tools for early DR screening and disease stage stratification remain inadequate. This study aimed to identify serum metabolic biomarkers for DR stage discrimination and to characterize metabolic alterations associated with DR onset and progression. Methods: Serum samples from four groups—healthy controls (HC), diabetic patients without retinopathy (NDR), patients with mild nonproliferative DR (NPDR), and patients with moderate-to-advanced DR (MADR)—were analyzed using untargeted metabolomics. Three pairwise comparisons were designed to identify key transition points in DR progression. Candidate biomarkers were screened by identifying differential metabolites and further optimized using logistic regression analysis. Results: Stage-specific metabolic reprogramming occurred during DR progression, and lipid metabolism dysregulation persisted throughout the disease course. The candidate biomarker panels achieved cross-validated area under the curve (AUC) values of 0.918, 0.800, and 0.893 for distinguishing NPDR from HC, NPDR from NDR, and MADR from NDR, respectively, demonstrating stable and robust diagnostic performance. Moreover, the identified biomarkers were significantly correlated with key clinical parameters of DR. Conclusions: This study provides promising blood-based candidate biomarkers and novel metabolic insights for early screening and progression monitoring of DR.

Definitions of nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated FLD (MAFLD), and steatotic liver disease (SLD) have been proposed to better guide clinical practice and epidemiological studies. The effects of the nomenclature on the incidence of FLD and its associations with obesity phenotypes, insulin resistance (IR), and liver fibrosis were examined in this study. NAFLD, MAFLD, and metabolic dysfunction-associated steatotic liver disease (MASLD) were diagnosed on the basis of ultrasound examination and metabolic disorders among 6,718 community-dwelling individuals from southeast China. Six obesity phenotypes, seven IR surrogates, and the NAFLD Fibrosis Score (NFS) were applied to evaluate their association with FLDs through multivariable logistic regression models, restricted cubic splines, and receiver operating characteristic curves. The prevalence of FLD, NAFLD, MAFLD, and MASLD was 35.47%, 33.34%, 34.77%, and 32.79%, respectively. The associations of obesity-FLD, IR-FLD, and FLD-NFS were statistically significant across all the FLD definitions. Patients with MAFLD demonstrated slightly higher odds ratios (ORs) than those with FLD, NAFLD, and MASLD. However, alcoholic-FLD (AFLD), which is included in the MAFLD nomenclature, showed lower ORs with obesity and IR and lower NFS, significantly differently from other FLDs. Among all obesity and IR indices, triglyceride and glucose index body mass index (TyG-BMI), the TyG-waist height ratio (TyG-WHtR), and the TyG-waist circumstance (TyG-WC) were the best at predicting FLDs and ORs with respect to NFS. The nomenclature of MAFLD covers a wider range of FLD than NAFLD and MASLD do, but the heterogeneity of AFLD is nonnegligible. Compared with MASLD, NAFLD remains a practical and efficient definition for large-scale population screening, especially in resource-limited settings. TyG-BMI, TyG-WHtR, and TyG-WC could better predict FLD and associated fibrosis, affirming their potential as simple and cost-effective tools to support health monitoring and early intervention.

Introduction: Various foods or food groups and nutrients are correlated with serum uric acid levels. However, the findings were not consistent across different populations, and the mechanisms remain unclear.Methods: In the baseline survey of the Fuqing Cohort, 4,326 participants were selected from Southeast coastal Chinese communities, and their dietary patterns were derived from a validated food frequency questionnaire using principal component analysis. Logistic regression was used to estimate the risk of hyperuricemia across the quintiles of each dietary pattern. Additionally, we performed mediation analysis to assess the potential mediating role of metabolic factors.Results: Based on the parallel analysis, four principal components were retained, explaining 46% of the total variance. Higher consumption of animal-based food (meat, fish, and seafood), bean products, sweets, desserts, and fried foods is significantly associated with an increased risk of hyperuricemia (Odds ratio for highest quintile of this dietary pattern vs. lowest: 1.36; 95% CI: 1.07, 1.72). Participants under 60 years showed a notably higher relative risk, which was significantly mediated by body mass index in combination with low-density lipoprotein and/or fatty liver.Conclusion: Greater adherence to a high-protein diet, along with fried food, sweets, and desserts, increases the risk of hyperuricemia, particularly in people under 60 years of age. Moderate consumption of an animal-based diet and significantly reducing the intake of sweets and fried foods may help prevent the risk of hyperuricemia.

We aimed to assess the contribution of repeated fasting blood glucose (FBG) measurements along with single collection of 2-hour postprandial glucose (2h PG) and glycated hemoglobin (HbA1c) on diabetes mellitus (DM) prevalence estimation, and investigate the association between the insulin-related markers and DM risk in a southeastern Chinese population. We included 6515 participants aged 35-75 years with complete glycemic data. McNemar's test was utilized to compare the difference between WHO and ADA criteria in DM diagnosis. Newly diagnosed DM cases were classified as 1defect (DEF), 2DEF, or 3DEF DM according to the abnormalities of three glycemic indices. The sensitivity and specificity of diagnosing DM using different glycemic markers were assessed. The association between different index and DM was analyzed using log-binomial regression and receiver operating characteristic curves. The age- and sex-standardized prevalence of DM was 14.0% and 14.7% by the WHO and ADA criteria, respectively. 2h PG, HbA1c, and FBG detected 89.65%, 40.69%, and 15.24% of newly diagnosed DM population, respectively. . All cases identified by repeated FBG were also detected by either 2h PG or HbA1c. The disposition index showed the highest area under the curve (0.82) in DM prediction, followed by the product of triglyceride and fasting glucose (TyG, 0.72). The estimated previous diagnosis, treatment, and control rate of DM was 38.6%, 34.9%, and 29.4%, respectively. It is recommended that 2h PG and HbA1c should be used in population-based studies. The disposition index and TyG could potentially be used as DM predictors.

Objective: To describe the prevalence of thyroid nodules (TNs), their ultrasonographic characteristics, and the cancer risk assessment using the Thyroid Imaging Reporting and Data System (TIRADS) in a natural population, while also exploring their association with multiple metabolic disorders. This study aims to provide insight into the disease burden of TNs in the coastal area of Southeast China.Design: A cross-sectional study.Setting and participants: A total of 6221 participants from the baseline survey of the Fuqing Cohort Study, an ongoing population-based study in a coastal city of Southeast China, were included.Primary and secondary outcome measures: TNs and its detailed ultrasonographic characteristics, risk grading in TIRADS, and metabolic factors.Results: The age- and sex-standardized prevalence of TNs was found to be 67.2%, with a higher prevalence observed in females and an increase with age. Additionally, multiple, solid, and < 10 mm TNs were common. Approximately 39.2% of participants were diagnosed with grade 3, while 2.3% were classified as grade ≥ 4a according to TIRADS. Metabolic syndrome was associated with TNs, but this association was significant only in females. The relationship between metabolic disorders and the characteristics and grade of TNs in TIRADS varied by sex.Conclusion: The prevalence of TNs in the coastal area of Southeast China is notable, with 2.3% of the population classified as grade ≥ 4a in TIRADS, indicating a high risk of cancer and necessitating further assessment for thyroid cancer. The association between TNs and metabolic disorders varies by sex and requires further confirmation.

Background: Hypertension remains a leading cause of cardiovascular morbidity and mortality globally, and insulin resistance (IR) and systemic inflammation are implicated in the pathogenesis of hypertension. Limited evidence exists on the predictive role of the triglyceride-glucose (TyG) index and its related indices (TyG-WHtR and TyG-WC) for hypertension. This study aimed to investigate these associations across multiple Chinese cohorts. Methods: Data from 31,224 participants (Fuqing, CHNS, CHARLS) were analyzed. TyG indices were calculated using fasting triglycerides, glucose, and anthropometrics. Hypertension was defined as SBP/DBP ≥ 140/90 mmHg, or physician diagnosis, or antihypertensive treatment. Logistic/Cox regression models were used to examine associations, adjusting for demographics, lifestyle, and metabolic factors. Mediation analysis quantified the role of neutrophil-to-lymphocyte ratio (NLR) in mediating the TyG–hypertension relationship. Results: Elevated TyG index and its obesity-adjusted variants consistently predicted incident hypertension across cohorts (all p < 0.001). Each 1-unit TyG increase was associated with 9–36% higher odds of hypertension in Fuqing (OR = 1.09–1.36). NLR mediated 20.4–29.4% of these associations (p < 0.001). Subgroup analyses revealed effect modifications by age, sex, and residence. Sensitivity analyses confirmed robustness when redefining hypertension thresholds (ACC/AHA criteria). Conclusions: TyG index and its related indices are robust predictors of (new-onset) hypertension, with NLR statistically accounting for approximately 25% of these associations in the mediation model. These findings underscore the interplay between metabolic dysregulation, inflammation, and hypertension and advocate for integrated biomarker strategies in risk stratification and prevention, while external validation in multi-ethnic populations is warranted.

Purpose To evaluate the reproducibility and validity of a 93-item food frequency questionnaire (FFQ) designed to assess usual dietary habits over the past year among adults in the southeast coastal region of China. Methods Qualified dietary data of 477 subjects (75.26% female, mean age = 59.7 years) were collected via two FFQs over approximately 15 months, alongside four 4-day 24-hour dietary recalls (24 h-DRs) at average intervals of four months. The analysis included 25 general nutrients, 14 particular nutrients and 12 food groups. Wilcoxon signed-rank test, correlation coefficients, cross-classification with weighted kappa statistic and Bland–Altman plots were used for comparison. Results For reproducibility, the Spearman, Pearson, and intraclass correlation coefficients between two FFQs ranged from 0.24 to 0.53, 0.21 to 0.53 and 0.19 to 0.53, respectively. After adjusting for energy intake, most coefficients either decreased or remained unchanged. The rates of agreement in classifying subjects in the same or adjacent quartile fell between 62% and 84% for both FFQs. Regarding validity, the crude Spearman, energy-adjusted and de-attenuated Pearson correlation coefficients between FFQs and 24 h-DRs ranged from 0.17 to 0.59, 0.12 to 0.54, and 0.13 to 0.57, respectively. Over 58% of subjects were classified into the same and adjacent categories by both methods. Weighted kappa statistic and Bland-Altman plots demonstrated acceptable concordance. Conclusion The FFQ developed for adults in the specific coastal region of China, aiming to be used in a population-based cohort study, demonstrates acceptable reproducibility and validity to measure the dietary intakes of certain nutrients and foods.

Background: Dietary patterns influence women's risk of breast cancer, but few studies have investigated the association with benign breast nodules, a well-established risk factor for breast cancer, especially by subtypes of the disease.Methods: A cross-sectional study of 3,483 women enrolled in the Fuqing Cohort Study in southeast China was conducted from 2020 to 2021. Dietary patterns were identified from food frequency questionnaires using principal component analysis, and the scores for these patterns were divided into quartiles. Univariate and multivariate logistic regression models were used to calculate odds ratios (OR) with 95% confidence interval (CI) for the association between dietary patterns and benign breast nodules.Results: We found four dietary patterns among the women: animal-based dietary pattern, plant-based dietary pattern, fried food/dessert pattern, and nuts pattern. Compared with the lowest quartile, women in the highest quartile of the scores for the animal-based dietary pattern were more likely to have cystic breast nodules (OR = 1.61, 95% CI = 1.12–2.32, and the P-value for trend test = 0.007), especially in postmenopausal women. In addition, women with a high score for fried food/dessert pattern also had higher odds of breast cystic nodules (P-value for trend test = 0.012), with an OR (95% CI) of 1.46 (1.01–2.09) for the fourth quartile group. However, there were no associations between these dietary patterns and solid breast nodules.Conclusion: Animal-based dietary pattern and fried food/dessert pattern were positively associated with cystic breast nodules. These findings suggested the role of unhealthy dietary habits in the development of breast nodules.

Purpose: We aimed to identify the association between obesity and nonalcoholic fatty liver disease (NAFLD) and to quantify the mediating effects of insulin resistance (IR) and chronic inflammation through observational studies and Mendelian randomization (MR). Patients and Methods: In the current study, three IR-related indicators and three indicators of inflammation were included. The individual and combined mediated effects of IR and inflammation in the association between obesity and NAFLD were investigated in two cross-sectional studies, the Fuqing Cohort from China and the National Health and Nutrition Examination Survey (NHANES). Total, direct, and indirect effects were estimated through direct counterfactual imputation estimation, and the proportion of mediating effects was calculated. We applied a two-step MR to determine the causal mediating role of IR and chronic inflammation in the pathway between obesity and NAFLD by using single nucleotide polymorphisms as instrumental variables to predict obesity, IR, and inflammation genetically. Results: In the Fuqing Cohort, all obese phenotypes were associated with an elevated NAFLD risk. Moreover, indicators of IR such as homeostatic model assessment of insulin resistance (HOMA-IR) and indicators of inflammation such as C-reactive protein (CRP) were significantly and positively associated with NAFLD risk. Individuals with obesity had significantly higher levels of IR and inflammation indicators compared to non-obese individuals. The indirect proportions of insulin and HOMA-IR accounted for 50.97– 66.72% in the associations between obese phenotypes and NAFLD risk, while the proportions of inflammation indicators were < 14%. Similar results were observed in the NHANES analysis. In the MR analysis, the indirect effects of HOMA-IR and CRP were statistically significant with a greater mediated proportion explained by HOMA-IR than CRP. Conclusion: Through two population-based studies and MR, we found the causal mediation roles of IR and inflammation in the association between obesity and NAFLD, in which HOMA-IR and CRP showed stable, significant mediation effects. Furthermore, HOMA-IR showed a higher mediation effect than CRP. We emphasize the vital role of HOMA-IR in NAFLD monitoring.