Associations of Serum 25-hydroxyvitamin D and Vitamin D Receptor Polymorphisms with Risks of Cardiovascular Disease and Mortality among Patients with Chronic Kidney Disease: A Prospective Study.

BACKGROUND: Evidence regarding the relationships of serum 25-hydroxyvitamin D (25[OH]D) with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent. OBJECTIVE: This study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD. METHODS: This prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality. RESULTS: The median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D <25 nmol/L, those with serum 25(OH)D ≥75 nmol/L had HRs (95% CIs) of 0.80 (0.71, 0.90) for total CVD incidence, 0.82 (0.69, 0.97) for ischemic heart disease, 0.56 (0.41, 0.77) for stroke, 0.64 (0.46, 0.88) for myocardial infarction, 0.62 (0.49, 0.80) for heart failure, 0.60 (0.43, 0.85) for CVD mortality, and 0.62 (0.52, 0.74) for all-cause mortality. In addition, these associations were not modified by VDR polymorphisms, with no significant interaction was detected. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total and subtypes of CVD incidence and mortality among individuals with CKD. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of CVD and mortality in patients with CKD.

Social isolation and the risk of Parkinson disease in the UK biobank study.

Parkinson disease (PD) has become one of the most rapidly growing causes of disability among the older population and social isolation is a major concern in the PD community. However, the relationship between social isolation and future risk of PD remains unclear. This study included 192,340 participants aged 60 or older who were free of dementia and PD at baseline from the UK Biobank study. Social isolation was measured using a composite score derived from three questions on number in household, frequency of friend/family visits, and leisure/social activities. Incident PD cases were identified through electronic health records. Multivariable-adjusted Cox regression models were used to compute the hazard ratio (HR) and 95% confidence interval (CI). Among the 192,340 participants (mean [standard deviation] age, 64.2 [2.9] years; 103,253 [53.7%] women), 89,075 (46.3%) participants were in the least isolated group and 26,161 (13.6%) were in the most isolated group. Over a median follow-up of 12.5 years, 2048 incident PD cases were documented. Compared to the least isolated group, the multivariable-adjusted HRs (95% CIs) for PD were 1.00 (0.91-1.10) for the moderately isolated group and 1.19 (1.05-1.36) for the most isolated group (P-trend = 0.04). The observed association was independent of the genetic susceptibility to PD and consistent in subgroup analyses. Social isolation was associated with a higher risk of PD regardless of genetic risk. Our findings highlighted the importance of developing screening and intervention strategies for social isolation among older adults to reduce the risk of PD.

Association of Ultraprocessed Food Consumption with Risk of Cardiovascular Disease Among Individuals with Type 2 Diabetes: Findings from the UK Biobank.

SCOPE: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. METHODS AND RESULTS: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, C-reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD. CONCLUSION: Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.

Trends in Calcium Intake among the US Population: Results from the NHANES (1999-2018).

Inadequate calcium intake is common in the US. Trends in calcium intake among the US population have been less studied, especially in more recent years. We used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 to 2017-2018 to study trends in calcium derived from diet and dietary supplements among the US population aged 2 years, stratified by sex, age group, race, and ethnicity. Among the 80,880 participants included in our study, a substantial portion consistently lacked sufficient calcium intake, even when considering calcium from supplements. Concerning trends were observed over the more recent ten years (2009-2018), with decreased dietary calcium intake and no significant improvement in the prevalence of dietary calcium intake < Estimated Average Requirement (EAR) or the prevalence of taking calcium-containing dietary supplements among them. Decreasing trends in dietary calcium intake were more concerning among men, children, and non-Hispanic Whites. Attention should be given to subgroups with higher calcium intake requirements (e.g., 9-18 years and 60+ years), and subgroups with low levels of dietary calcium and a low prevalence of obtaining calcium from dietary supplements (e.g., the non-Hispanic Black subgroup). Concerning trends of calcium intake were observed among the US population from 2009 to 2018. Tailored guidance on dietary choices and dietary supplement use is required to change consumers' behaviors.

Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study.

BACKGROUND: The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes. METHODS: In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m2. Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI). RESULTS: After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65-0.92), cholate (OR per SD: 0.78; 95% CI: 0.66-0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69-0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68-0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69-0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed. CONCLUSIONS: Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes.

Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study.

BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D. CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease: an observational and Mendelian randomization analysis.

BACKGROUND: Clinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDL-C) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks. METHODS: We included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC. RESULTS: Observational analyses showed L-shaped associations of HDL-C with CVD, with no further risk reduction when HDL-C levels exceeded 70 mg/dL. Multivariable MR analyses across entire distribution of HDL-C found no association of HDL-C with CVD, after control of the pleiotropic effect on other lipids and unmeasured pleiotropism. However, in stratified MR analyses, significant inverse associations of HDL-C with CVD were observed in the stratum of participants with HDL-C ≤ 50 mg/dL (odds ratio per unit increase, 0.86; 95 % confidence interval, 0.79-0.94), while null associations were observed in any stratum above 50 mg/dL. CONCLUSIONS: Our data suggest a potentially causal inverse association of HDL-C at low levels with CVD risks. These findings advance our knowledge about the role of HDL as a potential target in CVD prevention and therapy.

UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors.

The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

Beverage Consumption, Genetic Predisposition, and Risk of Cardiovascular Disease among Adults with Type 2 Diabetes.

BACKGROUND: The evidence regarding the relationship between different types of beverages and cardiovascular health in individuals with type 2 diabetes (T2D) is scarce. AIMS: To prospectively examine the associations between individual beverage consumption, genetic predisposition, and risk of incident cardiovascular disease (CVD) among adults with T2D. METHODS: We analyzed the associations of individual beverage intake with risks of CVD and ischemic heart disease (IHD) in 7315 participants with T2D, overall or stratified by genetic risk to CVD, using data from the UK Biobank study. RESULTS: During a median follow-up of 6.1 years, 878 incident CVD cases were identified, including 517 IHD cases. Higher intakes of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices were each linearly associated with a higher CVD (Pnonlinearity > 0.05). Comparing the highest to lowest groups of beverage consumption, the multivariable-adjusted HRs (95% CIs) of CVD were 1.54 (1.14, 2.07) for SSBs, 1.34 (1.07, 1.69) for ASBs, and 1.33 (1.01, 1.76) for natural juices. Similar results were observed for incident IHD. Moreover, no significant interactions between these beverages and the CVD genetic risk score were observed. Replacing half-unit/day of SSBs or natural juices with coffee, tea, or yogurt, but not ASBs, was associated with a 20%-46% lower risk of CVD and IHD. INTERPRETATION: Higher intakes of SSBs, ASBs, and natural juices were each linearly associated with an increased risk of CVD among individuals with T2D, regardless of genetic predisposition. Our findings highlight the importance of selecting healthy beverage options to improve cardiovascular health in patients with T2D.

Depressive symptoms, lifestyle behaviors, and risk of cardiovascular disease and mortality in individuals of different socioeconomic status: A prospective cohort study.

BACKGROUND: Depression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association. METHODS: This study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment. RESULTS: During 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive symptoms (versus without) was more pronounced as SES decreased, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.30 (1.22, 1.39), 1.27 (1.17, 1.37), and 1.17 (0.97, 1.41) in participants of low, medium, and high SES, respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.16 (1.07, 1.26), 1.21 (1.08, 1.36), and 1.24 (0.95, 1.61). In addition, multiple lifestyle factors together explained 14.4% to 32.8% of the elevated CVD and mortality risk due to depressive symptoms. LIMITATIONS: Moderate sensitivity of PHQ-2, lacked information on the severity of depression, baseline measurement of lifestyle. CONCLUSIONS: Depressive symptoms were associated with higher risks of incident CVD and mortality, especially in low SES groups, and lifestyle behaviors only explained a moderate proportion of the association. These findings indicated that health policies targeting healthy lifestyle promotion alone might not be sufficient, and other measures tackling social inequity are warranted to attenuate the elevated health risk due to depression.

Nuclear Magnetic Resonance-Based Metabolomics and Risk of CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY: The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Associations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes.

OBJECTIVE: To prospectively examine the associations of habitual calcium supplementation with cardiovascular disease (CVD) events and mortality in individuals with and without diabetes. RESEARCH DESIGN AND METHODS: The main analysis included 434,374 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales. RESULTS: Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR 1.34; 95% CI 1.14, 1.57), CVD mortality (HR 1.67; 95% CI 1.19, 2.33), and all-cause mortality (HR 1.44; 95% CI 1.20, 1.72) in participants with diabetes, whereas no significant association was observed in participants without diabetes (HR 0.97 [95% CI 0.92, 1.03] for CVD incidence; HR 1.05 [95% CI 0.90, 1.23] for CVD mortality; HR 1.02 [95% CI 0.96, 1.09] for all-cause mortality). Significant multiplicative and additive interactions were found between habitual calcium supplementation and diabetes status on risks of CVD events and mortality (all Pinteraction < 0.05). In contrast, no significant interactions were observed between dietary or serum calcium and diabetes status. CONCLUSIONS: Habitual use of calcium supplements was significantly associated with higher risk of CVD events and mortality in people with diabetes but not in people without diabetes. Further studies are needed to balance potentially adverse effects of calcium supplement against likely benefits, particularly among patients with diabetes.

Life's Essential 8 and heart failure among patients with chronic kidney disease: the Kailuan Cohort Study.

AIMS: Patients with chronic kidney disease (CKD) are at an increased risk of developing heart failure. The American Heart Association recently released a new metric, Life's Essential 8 (LE8), for health promotion. However, evidence regarding associations between LE8 and heart failure risk among patients with CKD is scarce. METHODS: A total of 16,190 patients with CKD (mean age 55.9 years), free of cardiovascular disease at recruitment from the Kailuan study, were included. Cardiovascular health was assessed using the LE8 score. Incident heart failure events were ascertained via linkage of electronic health record data. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 814 (5.0%) patients in the high LE8 criteria, with 13,180 (81.4%) in the moderate, and 2,196 (13.6%) in the low LE8 category, respectively. During a median follow-up of 13.7 years, 724 incident heart failure cases were documented. Compared with the low LE8 category, the HRs (95% CIs) for heart failure were 0.58 (0.48, 0.71) for the moderate LE8 category, and 0.32 (0.19, 0.54) for the high LE8 category (P for trend <0.001). In addition, the association was stronger in patients aged ≤65 years compared with their older counterparts (P for interaction = 0.01). CONCLUSION: Our data showed a strong graded inverse association between the LE8-defined cardiovascular health and the risk of heart failure among patients with CKD. Our findings support the importance of adopting the LE8 among patients with CKD to prevent heart failure.

Using the Life's Essential 8 (LE8) score, released by the American Heart Association for cardiovascular health promotion, this study investigated the relationship between cardiovascular health and the risk of heart failure in patients with chronic kidney disease (CKD) in China. Patients with CKD who had better cardiovascular health, as indicated by higher LE8 scores, had a significantly lower risk of heart failure.A stronger association between better LE8 score and lower risk of heart failure among CKD patients aged ≤65 years was observed, compared with their older counterparts.

Adherence to a Planetary Health Diet, Environmental Impacts, and Mortality in Chinese Adults.

Importance: Although the EAT-Lancet Commission has recently proposed a planetary health diet (PHD) to promote human and environmental health, little is known about how PHD affects environment and mortality risk among an Asian population. Objective: To investigate whether a PHD score is associated with environmental impacts and mortality outcomes in a Chinese cohort living in Singapore. Design, Setting, and Participants: This cohort study used data from the Singapore Chinese Health Study. Eligible participants were without known cardiovascular disease and cancer at baseline; they were recruited between 1993 and 1998 and followed up using record linkage data until 2020. Data were analyzed from September 2022 to April 2023. Exposures: PHD score was calculated based on the reference consumption of 14 dietary components in PHD and individual energy intake assessed using a validated food frequency questionnaire in this cohort. Main Outcomes and Measures: Diet-related environmental impacts were estimated using a food frequency questionnaire. Mortality outcomes (all-cause, cardiovascular disease, cancer, and respiratory disease) were identified via linkage with a nationwide registry. Results: A total of 57 078 participants were included in this study (mean [SD] age, 56.1 (7.9) years; 31 958 women [56.0%]). During a median (IQR) follow-up of 23.4 (18.7-26.2) years, 22 599 deaths occurred. Comparing the highest and lowest quintiles, higher PHD scores were associated with lower greenhouse gas emissions (ß = -0.13 kg CO2 equivalent; 95% CI, -0.14 to -0.12 kg CO2 equivalent), but with higher total water footprint (ß = 0.12 m3; 95% CI, 0.11-0.13 m3) and land use (ß = 0.29 m2; 95% CI, 0.28-0.31 m2). In the adjusted multivariable model, compared with the lowest quintile, participants in the highest quintile of PHD score had lower risk of all-cause mortality (hazard ratio [HR], 0.85; 95% CI, 0.81-0.89), cardiovascular disease mortality (HR, 0.79; 95% CI, 0.73-0.85), cancer mortality (HR, 0.93; 95% CI, 0.86-1.00), and respiratory disease mortality (HR, 0.81; 95% CI, 0.74-0.89). Conclusions and Relevance: In this study of Singapore Chinese adults, higher adherence to PHD was associated with reduced risk of chronic disease mortality. However, environmental impacts were uncertain, as higher adherence was associated with lower greenhouse gas emissions but higher total water footprint and land use.

Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.

BACKGROUND: Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear. OBJECTIVES: This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers. METHODS: The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014). Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: After 35,632 person-y of follow-up, 1174 deaths were documented. Higher nut consumption was significantly associated with a lower risk of all-cause mortality among individuals with T2D. After multivariable adjustment including lifestyles and dietary factors, diabetes duration, and glycated hemoglobin, compared with participants who did not consume nuts, the HR (95% CI) for those who consumed nuts over 3.5 ounce equivalent (oz.eq)/wk was 0.64 (0.50, 0.82; P-trend < 0.001) for all-cause mortality. A linear dose-response relationship was observed between nut consumption and all-cause mortality among individuals with T2D (Poverall=0.004, Pnonlinearity=0.35). In substitution analyses, replacing one serving of red and processed meat, refined grains, eggs, and dairy foods with one serving of nuts was associated with a 18% to 22% lower risk of all-cause mortality. In addition, mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.7% and 9.1% of the relationship between nut consumption with all-cause mortality, respectively. CONCLUSIONS: Higher nut consumption was significantly associated with lower all-cause mortality among individuals with T2D. These findings indicate a potential benefit of nut consumption in the prevention of premature death among individuals with T2D.

Lactobacillus rhamnosus GG ATCC53103 and Lactobacillus plantarum JL01 improved nitrogen metabolism in weaned piglets by regulating the intestinal flora structure and portal vein metabolites.

At present, most studies have shown that probiotics have a positive regulatory effect on the nutritional metabolism of the body, but the mechanism is still unclear. Here, 48 piglets were divided into four groups. The control group was not fed probiotics, the Lac group was fed L. Rhamnosus GG ATCC53103, the Rha group was fed L. Plantarum JL01, and the mix group was fed two types of probiotics. Nitrogen metabolism and mRNA levels of mTOR and S6K in skeletal muscle were observed in each group. Then, metagenome and non-targeted metabonomics were used to observe the changes of intestinal microorganisms and plasma metabolites in portal channels after probiotics feeding. Finally, we combined the results of omics analysis to reveal the mechanism of probiotics on nitrogen metabolism in weaned piglets. The results showed that L. Rhmnosus GG ATCC53103 and L. Plantarum JL01 increased nitrogen apparent digestibility, nitrogen deposition rate, and nitrogen utilization rate of weaned piglets (P < 0.05); the relative expression of mTOR and SK6 mRNA in skeletal muscle increased significantly (P < 0.05). When L. rhamnosus GG ATCC53103 and L. plantarum JL01 were combined, we found that Clostridium and Prevotella significantly increased in the jejunum (P < 0.05). The relative abundance of Lactobacillus, Ruminococcus, Streptococcus, and Prevotella in the ileum increased significantly (P < 0.05). Compared with the control group, L-Tryptophan, 3-Phosphonyloxypyruvate, cis-Aconitate, and Carbamoyl phosphate were significantly increased in the mixed group portal vein. The result of the combinatorial analysis showed that the significantly increased microorganisms could encode the enzyme genes for the synthesis of L-Tryptophan, 3-Phosphonooxypyruvate, cis-Aconitate, and Carbamoyl phosphate. In summary, our results demonstrated that L. Rhamnosus GG ATCC53103 and L. Plantarum JL01 could stimulate the expression of skeletal muscle protein synthesis genes of weaned piglets by modulating the structure of the gut microbiota and its metabolites, thereby improving nitrogen metabolism in weaned piglets.

Trends in Self-Reported Adherence to Healthy Lifestyle Behaviors Among US Adults, 1999 to March 2020.

Importance: Adherence to a healthy lifestyle is associated with lower risks of adverse outcomes. However, trends in multiple lifestyle factors and overall healthy lifestyle status among US adults in recent years are unknown. Objective: To examine trends in multiple lifestyle factors and overall healthy lifestyle among US adults. Design, Setting, and Participants: This serial cross-sectional study used nationally representative data from 10 National Health and Nutrition Examination Survey (NHANES) cycles (nine 2-year cycles from 1999 to 2016 and 1 combined cycle from 2017 to March 2020) among adults 20 years or older. Data were analyzed from December 10, 2021, to January 11, 2023. Exposure: Survey cycle. Main Outcomes and Measures: Five healthy lifestyle factors: never smoking, moderate or lighter alcohol consumption (for women: ≤7 drinks/wk; for men: ≤14 drinks/wk), healthy diet (Healthy Eating Index-2015 scores ≥60.0), sufficient physical activity (≥150 min/wk of equivalent moderate physical activity), and healthy weight (body mass index [calculated as weight in kilograms divided by height in meters squared] 18.5-24.9). Results: A total of 47 852 adults were included in this study. The weighted mean [SE] age was 47.3 [0.2] years; 24 539 (weighted proportion, 51.5%) were women. From the 1999-2000 cycle to the 2017 to March 2020 cycle, the estimated prevalence of the 5 lifestyle factors showed divergent trends, with increasing prevalence of never smoking (from 49.4% [95% CI, 46.4%-52.4%] to 57.7% [95% CI, 55.5%-59.9%]; difference, 8.2% [95% CI, 4.5%-12.0%]), healthy diet (from 19.3% [95% CI, 16.0%-22.6%] to 24.5% [95% CI, 21.5%-27.5%]; difference, 5.2% [95% CI, 0.8%-9.7%]), and sufficient physical activity (from 55.7% [95% CI, 51.8%-59.6%] to 69.1% [95% CI, 67.2%-71.1%]; difference, 13.4% [95% CI, 9.0%-17.8%]), while prevalence of healthy weight decreased from 33.1% (95% CI, 30.5%-35.6%) to 24.6% (95% CI, 22.6%-26.7%; difference, -8.4% [95% CI, -11.8% to -5.1%]) (all P < .001 for trend). Meanwhile, there was no significant trend in moderate or lighter alcohol consumption. Overall, the estimated prevalence of at least 4 healthy lifestyle factors increased from 15.7% (95% CI, 12.8%-18.7%) to 20.3% (95% CI, 17.8%-22.7%; difference, 4.5% [95% CI, 0.7%-8.4%]; P < .001 for trend). Disparities in healthy lifestyle were widened by age group, with little improvement among adults 65 years and older (difference, 0.04% [95% CI, -4.28% to 4.35%]). There were persistent disparities in healthy lifestyle by race and ethnicity, educational level, and income level. Conclusions and Relevance: The findings of this cross-sectional study of NHANES data over a 22-year period suggest diverse change patterns across 5 healthy lifestyle factors and a modest improvement in overall lifestyle existed among US adults, with worsening or persistent disparities in lifestyle.

Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines.

The powerful immune responses elicited by the mRNA vaccines targeting the SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, their efficacy can vary greatly between individuals. For vaccines not based on mRNA, cumulative evidence suggests that differences in the composition of the gut microbiome, which impact vaccine immunogenicity, are some of the factors that contribute to variations in efficacy. However, it is unclear if the microbiome impacts the novel mode of immunogenicity of the SARS-CoV-2 mRNA vaccines. We conducted a prospective longitudinal cohort study of individuals receiving SARS-CoV-2 mRNA vaccines where we measured levels of anti-Spike IgG and characterized microbiome composition, at pre-vaccination (baseline), and one week following the first and second immunizations. While we found that microbial diversity at all timepoints correlated with final IgG levels, only at baseline did microbial composition and predicted function correlate with vaccine immunogenicity. Specifically, the phylum Desulfobacterota and genus Bilophila, producers of immunostimulatory LPS, positively correlated with IgG, while Bacteroides was negatively correlated. KEGG predicted pathways relating to SCFA metabolism and sulfur metabolism, as well as structural components such as flagellin and capsular polysaccharides, also positively correlated with IgG levels. Consistent with these findings, depleting the microbiome with antibiotics reduced the immunogenicity of the BNT162b2 vaccine in mice. These findings suggest that gut microbiome composition impacts the immunogenicity of the SARS-CoV-2 mRNA vaccines.

Associations of Glucose Metabolism Status with Brain Macrostructure and Microstructure: Findings from the UK Biobank.

CONTEXT: Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. OBJECTIVE: We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. METHODS: This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate ß values and 95% CI. RESULTS: After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (ß -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c ≥ 7% (all P trend < .05), except for FA values in projection fibers. CONCLUSION: These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.