Longitudinal blood glucose level and increased silent myocardial infarction: a pooled analysis of four cohort studies.

BACKGROUND: Fasting glucose (FG) demonstrates dynamic fluctuations over time and is associated with cardiovascular outcomes, yet current research is limited by small sample sizes and relies solely on baseline glycemic levels. Our research aims to investigate the longitudinal association between FG and silent myocardial infarction (SMI) and also delves into the nuanced aspect of dose response in a large pooled dataset of four cohort studies. METHODS: We analyzed data from 24,732 individuals from four prospective cohort studies who were free of myocardial infarction history at baseline. We calculated average FG and intra-individual FG variability (coefficient of variation), while SMI cases were identified using 12-lead ECG exams with the Minnesota codes and medical history. FG was measured for each subject during the study's follow-up period. We applied a Cox regression model with time-dependent variables to assess the association between FG and SMI with adjustment for age, gender, race, Study, smoking, longitudinal BMI, low-density lipoprotein level, blood pressure, and serum creatinine. RESULTS: The average mean age of the study population was 60.5 (sd: 10.3) years with median fasting glucose of 97.3 mg/dL at baseline. During an average of 9 years of follow-up, 357 SMI events were observed (incidence rate, 1.3 per 1000 person-years). The association between FG and SMI was linear and each 25 mg/dL increment in FG was associated with a 15% increase in the risk of SMI. This association remained significant after adjusting for the use of lipid-lowering medication, antihypertensive medication, antidiabetic medication, and insulin treatment (HR 1.08, 95% CI 1.01-1.16). Higher average FG (HR per 25 mg/dL increase: 1.17, 95% CI 1.08-1.26) and variability of FG (HR per 1 sd increase: 1.23, 95% CI 1.12-1.34) over visits were also correlated with increased SMI risk. CONCLUSIONS: Higher longitudinal FG and larger intra-individual variability in FG over time were associated in a dose-response manner with a higher SMI risk. These findings support the significance of routine cardiac screening for subjects with elevated FG, with and without diabetes.

MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites.

Malaria remains one of the deadliest infectious diseases. Transcriptional regulation effects of noncoding variants in this unusual genome of malaria parasites remain elusive. We developed a sequence-based, ab initio deep learning framework, MalariaSED, for predicting chromatin profiles in malaria parasites. The MalariaSED performance was validated by published ChIP-qPCR and TF motifs results. Applying MalariaSED to ~ 1.3 million variants shows that geographically differentiated noncoding variants are associated with parasite invasion and drug resistance. Further analysis reveals chromatin accessibility changes at Plasmodium falciparum rings are partly associated with artemisinin resistance. MalariaSED illuminates the potential functional roles of noncoding variants in malaria parasites.

Higher serum vitamin A is associated with a worsened progression of non-alcoholic fatty liver disease in adults: a prospective study.

Background: The association between serum vitamin A and non-alcoholic fatty liver disease (NAFLD) remains uncertain due to inconsistent results and scarce longitudinal data. We examined the prospective associations between serum vitamin A and the evolution of the NAFLD severity score as well as the potential mediating effects in middle-aged and older Chinese adults. Method: A total of 2658 adults (between 40-75 years of age) were included in the analysis. We determined the serum concentrations of vitamin A at the onset of the study (the baseline), and the degree of NAFLD after years 3 and 6. Results: Subjects were classified into stable, progressed, and improved groups according to the changes in their severity score (0-3) of NAFLD between two visits. Analyses of covariance showed that the serum VA concentrations were positively associated with NAFLD progression (all p-trend < 0.05). After adjusting for potential confounders, the mean differences in the serum vitamin A were 7.7% lower in the improved group than those in the progressed group among the total population. Path analyses showed that vitamin A was positively associated with the serum retinol-binding protein 4, triglycerides, insulin resistance, and body mass index (standardized ß 0.065-0.304, all p < 0.001), and all of these factors positively correlated with the prevalence and progression of NAFLD (standardized ß 0.045-0.384, all p < 0.01). Conclusions: A higher serum vitamin A concentration was associated with NAFLD progression, which might be mediated by increases in the serum retinol-binding protein 4, triglycerides, insulin resistance, and body mass index.

Gut microbiota, inflammation, and molecular signatures of host response to infection.

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.

The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort.

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Erythrocyte Membrane Polyunsaturated Fatty Acids Are Associated with Incidence of Metabolic Syndrome in Middle-Aged and Elderly People-An 8.8-Year Prospective Study.

BACKGROUND: The total and specific types of polyunsaturated fatty acids (PUFAs) related to metabolic syndrome (MetS) remain inconsistent. OBJECTIVE: We assessed the association of erythrocyte n-3 and n-6 PUFAs with MetS and the components of MetS in a cohort population. METHODS: This prospective analysis included 2754 participants (aged 40-75 y) from the Guangzhou Nutrition and Health Study (2008-2019) in China. Erythrocyte PUFAs at baseline were measured using gas chromatography. MetS was assessed every 3 y according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariable Cox proportional hazard models were used to evaluate HRs and 95% CIs. RESULTS: We identified 716 incident cases of MetS. The primary analyses showed that the HRs (95% CIs) of MetS (tertile 3 versus 1) were 0.67 (0.56, 0.80) for n-3 PUFAs and 0.70 (0.58, 0.85) for n-6 PUFAs (all Ps trend <0.001). The secondary outcomes showed that, higher erythrocyte very-long-chain (VLC) PUFAs [20:3n-3, docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), and 22:4n-6], but lower α-linolenic acid (ALA) and γ-linolenic acid (GLA), tended to be associated with lower incidences of MetS and its components; among individual MetS components, the associations of PUFAs were more pronounced for hypertriglyceridemia (HTG) and hypertension, followed by low high-density lipoproten (HDL) cholesterol. Significantly higher concentrations of n-3 PUFAs (total, DPA, and DHA) and n-6 PUFAs (total, ARA, and 22:4) were observed in participants with improved (versus progressed) status of MetS (all Ps trend ≤0.003). CONCLUSION: This study reveals that higher erythrocyte VLC n-3 and n-6 PUFAs, but lower 18-carbon PUFAs (ALA and GLA), are associated with lower risks of MetS components (HTG, hypertension, and low HDL cholesterol) and thereby lower MetS incidence in Chinese adults.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and elderly adults.

OBJECTIVE: Previous studies have shown that the Dietary Approaches to Stop Hypertension (DASH) diet might contribute to managing risk factors of non-alcoholic fatty liver disease (NAFLD), but evidence is limited. We examined the association of DASH diet score (DASH-DS) with NAFLD, as well as the intermediary effects of serum retinol-binding protein-4 (RBP4), serum high-sensitivity C-reactive protein (hs-CRP), serum TAG, homeostasis model assessment of insulin resistance (HOMA-IR) and BMI. DESIGN: We performed a cross-sectional analysis of a population-based cohort study. Dietary data and lifestyle factors were assessed by face-to-face interviews and the DASH-DS was then calculated. We assessed serum RBP4, hs-CRP and TAG and calculated HOMA-IR. The presence and degree of NAFLD were determined by abdominal sonography. SETTING: Guangzhou, China. PARTICIPANTS: Guangzhou Nutrition and Health Study participants, aged 40-75 years at baseline (n 3051). RESULTS: After adjusting for potential covariates, we found an inverse association between DASH-DS and the presence of NAFLD (Ptrend = 0·009). The OR (95 % CI) of NAFLD for quintiles 2-5 were 0·78 (0·62, 0·98), 0·74 (0·59, 0·94), 0·69 (0·55, 0·86) and 0·77 (0·61, 0·97), respectively. Path analyses indicated that a higher DASH-DS was associated with lower serum RBP4, hs-CRP, TAG, HOMA-IR and BMI, which were positively associated with the degree of NAFLD. CONCLUSIONS: Adherence to the DASH diet was independently associated with a marked lower prevalence of NAFLD in Chinese adults, especially in women and those without abdominal obesity, and might be mediated by reducing RBP4, hs-CRP, TAG, HOMA-IR and BMI.

Erythrocyte membrane n-3 polyunsaturated fatty acids are inversely associated with the presence and progression of nonalcoholic fatty liver disease in Chinese adults: a prospective study.

PURPOSE: Previous studies have shown that high-dose supplementation with n-3 polyunsaturated fatty acids (PUFAs) may benefit patients with nonalcoholic fatty liver disease (NAFLD), but the association of n-3 PUFAs with NAFLD among individuals with normal diets is only speculative. We investigated the cross-sectional and prospective associations between n-3 PUFAs and NAFLD in Chinese adults. METHODS: This community-based prospective study included 3049 men and women (40-75 years) in Guangzhou, China, whose participants completed an NAFLD ultrasound evaluation and erythrocyte PUFA tests. A total of 2660 participants underwent the second NAFLD evaluation approximately 3 years later. α-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes were measured by gas chromatography. RESULTS: After adjusting for potential confounders, we observed inverse associations between DHA, DHA + EPA, total n-3 PUFAs and the presence of NAFLD in the cross-sectional analysis. The adjusted odds ratios (95% confidence interval) of NAFLD for the highest (vs. lowest) tertile were 0.74 (0.61, 0.90) for DHA, 0.82 (0.67, 1.00) for EPA, 0.73 (0.60, 0.88) for DHA + EPA and 0.74 (0.61, 0.91) for total n-3 PUFAs  (all P values≤0.05). Over the average 3.12 years of follow-up, higher levels of DHA was associated with an improvement of NAFLD. The hazard ratio of improved NAFLD for the highest tertile was 1.18 (95% CI 1.09, 1.33) for DHA. Pathway analyses showed that favorable associations may be mediated by improvements in inflammatory markers (e.g., interleukin 1 beta and tumor necrosis factor alpha-like). CONCLUSIONS: Erythrocyte membrane n-3 PUFAs are inversely associated with the presence and progression of NAFLD in Chinese adults. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT03179657.

Association between Eating Away from Home and Hyperuricemia: A Population-Based Nationwide Cross-Sectional Study in China.

Hyperuricemia (HU) is a risk factor for different kinds of chronic noncommunicable diseases, and eating away from home (EAFH) may play an important role in their development, which has been ignored greatly so far. This study aimed to investigate the association between EAFH and HU in different models. A cross-sectional study involving 8,322 participants of the China Health and Nutrition Survey (CHNS) was conducted. Logistic regression models were used to analyze the data. We found that participants who consumed more away-from-home food had a higher risk for HU, and the adjusted odds ratio (aOR) and 95% confidence interval (CI) (for each increment in grades of EAFH) were 1.11 (1.02, 1.20) in a multiadjusted model (adjusted for age, gender, province, net individual income, body mass index, smoking, leisure-time physical activities, energy intake, and sleep duration). As for stratified analyses, the aOR (95% CI) of EAFH was 1.12 (1.01, 1.24) for men and 1.06 (0.92, 1.21) for women. Similar results can be found in the middle-aged and obese population, with aOR (95% CI) of EAFH as 1.17 (1.05, 1.30) and 1.15 (1.03, 1.29), respectively. In conclusion, EAFH is positively associated with the prevalence of HU.

Discovery and Validation of Circulating Hsa-miR-210-3p as a Potential Biomarker for Primary Open-Angle Glaucoma.

Purpose: Blood-based examination tools for glaucoma diagnosis in clinical practice, which can be useful for screening patients when traditional ophthalmic examinations cannot be utilized, are not available thus far. This study aimed to identify circulating microRNAs (miRNAs) associated with primary open-angle glaucoma (POAG) and explore their utility as diagnostic markers. Methods: A total of 136 POAG patients and controls were enrolled. Next-generation RNA sequencing was used to explore the expression profile of circulating miRNAs in the sequencing set, and potential miRNAs from independent samples in both the screening and validation sets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of certain miRNAs to distinguish POAG patients from control subjects. Results: Using sequencing and qRT-PCR, hsa-miR-210-3p was found to be elevated in POAG patients in all sets. ROC analysis of the screening and validation sets revealed that hsa-miR-210-3p differentiated between POAG patients and matched controls with an area under the curve (AUC) of 0.846 (sensitivity: 84.6%; specificity: 80.8%) and 0.813 (sensitivity: 84.8%; specificity: 69.7%), respectively. In case of all nonsequencing participants, analysis revealed that hsa-miR-210-3p differentiated between severe POAG patients and controls with an AUC of 0.880 (sensitivity: 85.4%; specificity: 85.7%). In addition, the expression of hsa-miR-210-3p was associated with visual field defects of |mean deviation| (ß = 0.237; P = 0.022) and average retinal nerve fiber layer thickness (ß = -5.792; P = 0.014). Conclusions: Circulating hsa-miR-210-3p may serve as a potential diagnostic marker for POAG (especially for severe POAG patients).

Higher serum carotenoids associated with improvement of non-alcoholic fatty liver disease in adults: a prospective study.

PURPOSE: Previous studies have suggested that serum carotenoids might be inversely associated with non-alcoholic fatty liver disease (NAFLD), but little data came from longitudinal studies. We prospectively examined the associations between serum-carotenoid levels and NAFLD severity and the intermediary effects of retinol-binding protein 4 (RBP4), HOMA insulin-resistance index (HOMA-IR), body mass index (BMI), and serum triglycerides in middle-aged and elderly Chinese adults. METHODS: This prospective study included 3336 Chinese adults (40-75 years). We assessed serum concentrations of carotenoids at baseline and determined serum RBP4, triglycerides, and HOMA-IR levels at year 3. Abdominal ultrasonography was conducted to assess the presence and degree of NAFLD at years 3 and 6. RESULTS: The 2687 subjects who completed both NAFLD tests were classified into stable, improved and progressed groups according to changes in the degree of NAFLD between two visits. Analyses of covariance showed that ln-transformed serum concentrations of α-carotene, ß-cryptoxanthin, ß-carotene, lycopene, lutein/zeaxanthin, and total carotenoids were positively associated with NAFLD improvement (all p-trend < 0.05). After multivariable adjustment, mean differences in serum carotenoids were higher by 29.6% (ß-carotene), 18.2% (α-carotene), 15.6% (ß-cryptoxanthin), 11.5% (lycopene), 8.9% (lutein/zeaxanthin), and 16.6% (total carotenoids) in the improved vs. progressed subjects. Path analyses indicated the carotenoid-NAFLD association was mediated by lowering serum RBP4, triglycerides, HOMA-IR, and BMI, which were positively associated with the prevalence and progression of NAFLD. CONCLUSIONS: In middle-aged and elderly adults, higher serum-carotenoid concentrations were favorably associated with NAFLD improvement, mediated by reducing serum RBP4, triglycerides, HOMA-IR, and BMI. TRIAL REGISTRATIONS: This study has been registered at http://www.clinicaltrials.gov as NCT03179657.

Serum Carotenoids Are Inversely Associated with RBP4 and Other Inflammatory Markers in Middle-Aged and Elderly Adults.

(1) Background: Carotenoids may be inversely associated with inflammatory markers (i.e., TNF-α, IL-6, IL-1ß). However, data are scarce on retinol binding protein 4 (RBP4) in humans. We examined the associations among serum carotenoids, RBP4 and several inflammatory markers in a Chinese population. (2) Methods: This community-based cross-sectional study included 3031 participants (68% males) aged 40-75 years in Guangzhou, China. Serum concentrations of carotenoids, RBP4, and inflammatory markers were measured. (3) Results: Generally, serum individual and total carotenoids were significantly and inversely associated with retinol-adjusted RBP4, RBP4, hsCRP, MCP1, and TNF-alpha levels. Age- and gender-adjusted partial correlation coefficients between total carotenoids and the above inflammatory markers were -0.129, -0.097, -0.159, -0.079, and -0.014 (all p < 0.01, except for TNF-alpha with p >0.05), respectively. The multivariate-adjusted values of partial correlation coefficients for these inflammation-related markers were -0.098, -0.079, -0.114, -0.090, and -0.079 (all p < 0.01), respectively. Among the individual carotenoids, those with the most predominant association were lutein-zeaxanthin and total carotenoids for retinol-adjusted RBP4 and RBP4, alpha- and beta-carotene for hsCRP, and alpha-carotene for MCP1 and TNF-alpha. No significant associations were observed for IL-6 and IL-1beta. (4) Conclusions: Serum carotenoids were inversely associated with RBP4, hsCRP, MCP1 and TNF-alpha among middle-aged and elderly Chinese adults.