Genetic association of inflammatory marker GlycA with lung function and respiratory diseases.

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (rg = -0.14), FVC (rg = -0.18), asthma (rg = 0.21) and COPD (rg = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/ß-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD.

Peripheral amyloid-ß clearance mediates cognitive impairment in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent risk factor for cognitive impairment. Cerebral amyloid-ß (Aß) accumulation, as an important pathology of cognitive impairment, can be caused by impaired Aß clearance in the periphery. The liver is the primary organ for peripheral Aß clearance, but the role of peripheral Aß clearance in NAFLD-induced cognitive impairment remains unclear. METHODS: We examined correlations between NAFLD severity, Aß accumulation, and cognitive performance in female Sprague-Dawley rats. The impact of NAFLD on hepatic Aß clearance and the involvement of low-density lipoprotein receptor-related protein 1 (LRP-1) were assessed in rat livers and cultured hepatocytes. Additionally, a case-control study, including 549 NAFLD cases and 549 controls (782 males, 316 females), investigated the interaction between NAFLD and LRP-1 rs1799986 polymorphism on plasma Aß levels. FINDINGS: The severity of hepatic steatosis and dysfunction closely correlated with plasma and cerebral Aß accumulations and cognitive deficits in rats. The rats with NAFLD manifested diminished levels of LRP-1 and Aß in liver tissue, with these reductions inversely proportional to plasma and cerebral Aß concentrations and cognitive performance. In vitro, exposure of HepG2 cells to palmitic acid inhibited LRP-1 expression and Aß uptake, which was subsequently reversed by a peroxisome proliferator-activated receptor α (PPARα) agonist. The case-control study revealed NAFLD to be associated with an increment of 8.24% and 10.51% in plasma Aß40 and Aß42 levels, respectively (both P < 0.0001). Moreover, the positive associations between NAFLD and plasma Aß40 and Aß42 levels were modified by the LRP-1 rs1799986 polymorphism (P for interaction = 0.0017 and 0.0015, respectively). INTERPRETATION: LRP-1 mediates the adverse effect of NAFLD on peripheral Aß clearance, thereby contributing to cerebral Aß accumulation and cognitive impairment in NAFLD. FUNDING: Major International (Regional) Joint Research Project, National Key Research and Development Program of China, National Natural Science Foundation of China, and the Angel Nutrition Research Fund.

Associations of Lower-Carbohydrate and Lower-Fat Diets with Mortality among People with Cardiovascular Disease.

BACKGROUND: Although low-carbohydrate and low-fat diets have been shown to have short-term metabolic benefits, the associations of these dietary patterns, particularly different food sources and macronutrient quality, with mortality in people with cardiovascular disease (CVD) remain unclear. OBJECTIVES: To examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality in individuals with CVD. METHODS: This study included 3971 adults with CVD from the NHANES 1999-2014. Mortality status was linked to National Death Index mortality data through 31 December 2019. Overall, unhealthy and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Higher healthy LCD score was associated with favorable blood lipids and higher homeostasis model assessment of insulin resistance, whereas higher unhealthy LFD score was associated with lower high-density lipoprotein and higher C-reactive protein at baseline (all P-trend < 0.05). During 35,150 person-years of follow-up, 2163 deaths occurred. For per 20-percentile increment in dietary scores, the multivariate-adjusted HRs of all-cause mortality were 0.91 (95% CI: 0.86, 0.96) for healthy LCD score (P < 0.001), 0.94 (95% CI: 0.89, 1.00) for healthy LFD score (P = 0.04), and 1.07 (95% CI: 1.00, 1.14) for unhealthy LFD score (P = 0.04). CONCLUSIONS: Overall LCD and LFD scores are not associated with total mortality. Unhealthy LFD scores are associated with higher total mortality, whereas healthy LCD and LFD scores are associated with lower mortality in people with CVD.

Genome-Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases.

Background Patients with rheumatoid arthritis (RA) have a 2- to 10-fold increased risk of cardiovascular disease (CVD), but the biological mechanisms and existence of causality underlying such associations remain to be investigated. We aimed to investigate the genetic associations and underlying mechanisms between RA and CVD by leveraging large-scale genomic data and genetic cross-trait analytic approaches. Methods and Results Within UK Biobank data, we examined the genetic correlation, shared genetics, and potential causality between RA (Ncases=6754, Ncontrols=452 384) and cardiovascular diseases (CVD, Ncases=44 238, Ncontrols=414 900) using linkage disequilibrium score regression, cross-trait meta-analysis, and Mendelian randomization. We observed significant genetic correlations of RA with myocardial infarction (rg:0.40 [95% CI, 0.24-0.56), angina (rg:0.42 [95% CI, 0.28-0.56]), coronary heart diseases (rg:0.41 [95% CI, 0.27-0.55]), and CVD (rg:0.43 [95% CI, 0.29-0.57]) after correcting for multiple testing (P<0.05/5). When stratified by frequent use of analgesics, we found increased genetic correlation between RA and CVD among participants without aspirin usage (rg:0.54 [95% CI, 0.30-0.78] for angina; Pvalue=6.69×10-6) and among participants with paracetamol usage (rg:0.75 [95% CI, 0.20-1.29] for myocardial infarction; Pvalue=8.90×10-3), whereas others remained similar. Cross-trait meta-analysis identified 9 independent shared loci between RA and CVD, including PTPN22 at chr1p13.2, BCL2L11 at chr2q13, and CCR3 at chr3p21.31 (Psingle trait<1×10-3 and Pmeta<5×10-8), highlighting potential shared pathogenesis including accelerating atherosclerosis, upregulating oxidative stress, and vascular permeability. Finally, Mendelian randomization estimates showed limited evidence of causality between RA and CVD. Conclusions Our results supported shared genetic pathogenesis rather than causality in explaining the observed association between RA and CVD. The identified shared genetic factors provided insights into potential novel therapeutic target for RA-CVD comorbidities.

Dose-Response Meta-Analysis on Risk of Diabetes in Relation to Red and Processed Meat Consumption - Asian Populations, 2006-2021.

What is already known about this topic?: Red and processed meat consumption has been positively related to an increased risk of diabetes in Western populations. However, the results remain inconclusive within Asian populations. What is added by this report?: This dose-response meta-analysis of prospective cohort studies conducted in East Asian populations reveals a positive relation between the consumption of processed meat and increased risk of diabetes. Furthermore, a U-shaped association was identified between the consumption of unprocessed red meat and the risk of diabetes. What are the implications for public health practice?: This research presents substantive evidence advocating for the reduction of processed and unprocessed red meat consumption as a viable strategy for mitigating the risk of diabetes in East Asian populations.

Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.

The role of peripheral ß-amyloid in insulin resistance, insulin secretion, and prediabetes: in vitro and population-based studies.

Background: Previous experimental studies have shown that mice overexpressing amyloid precursor protein, in which ß-amyloid (Aß) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Aß on insulin action and insulin secretion in vitro and the association of plasma Aß with prediabetes in human. Methods: We examined the effects of Aß40 and Aß42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses. Results: In the in vitro studies, Aß40 and Aß42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Aß40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Aß42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Aß40 and Aß42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively. Conclusion: Elevated plasma Aß40 and Aß42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic ß-cells.

Associations of lipoprotein subclasses with risk of all-cause and cardiovascular disease mortality in individuals with type 2 diabetes: A prospective cohort study.

AIM: Although lipoproteins are well-established risk factors for cardiovascular disease (CVD) mortality, conventional measurements failed to identify lipoprotein particle sizes. This study aimed to investigate associations of lipoprotein subclasses categorized by particle sizes with risk of all-cause and CVD mortality in individuals with type 2 diabetes. METHODS: This study included 6575 individuals with type 2 diabetes from the UK Biobank. Concentrations of very low-, low-, intermediate- and high-density lipoprotein [very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein and high-density lipoprotein (HDL)] particles in 14 subclasses and lipid constituents within each subclass were measured by quantitative nuclear magnetic resonance. Multivariable-adjusted Cox proportional-hazard regression models were used to estimate the hazard ratio (HR) for per standard deviation increment of log-transformed lipoprotein subclasses with risk of mortality. All p-values were adjusted by the false discovery rate method. RESULTS: During a median follow-up of 11.4 years, 943 deaths were documented, including 310 CVD deaths. Small HDL particles were inversely associated with CVD mortality, with HR (95% CI) of 0.78 (0.69, 0.87), whereas very large and large HDL particles were positively associated with CVD mortality with HR (95% CI) of 1.28 (1.12, 1.45) and 1.19 (1.05, 1.35), respectively. A similar pattern was observed for all-cause mortality [small HDL particle (HR, 95% CI): 0.79, 0.74-0.85; large HDL particle: 1.15, 1.07-1.24; very large HDL particle: 1.26, 1.17-1.36]. For VLDL and LDL, very small VLDL particle was positively, while medium LDL particle was inversely associated with all-cause mortality, but not associated with CVD mortality. The pattern of association with all-cause and CVD mortality for cholesterol and triglyceride within lipoprotein particles was similar to those for lipoprotein particles themselves. CONCLUSIONS: The associations between lipoprotein particles, particularly HDL particles, with all-cause and CVD mortality among patients with type 2 diabetes were significantly varied by particle sizes, highlighting the importance of particle size as a lipoprotein metric in mortality risk discrimination.

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.

Trends in the Prevalence of Metabolically Healthy Obesity Among US Adults, 1999-2018.

Importance: Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts. Objectives: To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups. Design, Setting, and Participants: This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022. Exposures: National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018. Main Outcomes and Measures: Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis. Results: This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend). Conclusions and Relevance: The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.

Blood trihalomethane concentrations and allergic sensitization: A nationwide cross-sectional study.

BACKGROUND: Exposure to disinfection by-products has been associated with several allergic diseases, but its association with allergen-specific immunoglobulin E (IgE) antibodies remains inconclusive. METHODS: We included 932 U.S. adolescents and 2187 adults from the National Health and Nutrition Examination Survey 2005-2006 who had quantified blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and 19 allergen-specific IgE antibodies. The odds ratios (ORs) of allergen-specific sensitization per 2.7-fold increment in blood THM concentrations were estimated by multivariable logistic regression models. RESULTS: Blood THM concentrations were unrelated to any allergen-specific sensitization in adults. Among adolescents, however, we found positive associations between blood TCM and chlorinated THMs (Cl-THMs: sum of TCM, BDCM, and DBCM) concentrations and the odds of pet sensitization [OR = 1.28 (95 % CI: 1.05, 1.55) and 1.38 (1.15, 1.65), respectively, per each 2.7-fold increment], between blood BDCM concentrations and the odds of mold [OR = 1.47 (1.24, 1.74)], plant [OR = 1.25 (1.09, 1.43)], pet [OR = 1.27 (1.07, 1.52)], and food sensitization [OR = 1.18 (1.03, 1.36)], and between blood brominated THM (Br-THMs: sum of BDCM, DBCM, and TBM) and total THM (TTHMs: sum of 4 THMs) concentrations and the odds of mold [OR = 1.52 (1.30 1.78) and 1.30 (1.03, 1.65), respectively], dust mite [OR = 1.39 (1.06, 1.82) and 1.45 (1.06, 1.98), respectively], and pet sensitization [OR = 1.42 (1.05, 1.92) and 1.54 (1.19, 1.98), respectively]. CONCLUSION: Higher blood concentrations of THMs were associated with a greater risk of allergic sensitization among U.S. adolescents but not in adults.

Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality.

Importance: The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality. Objective: To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality. Design, Setting, and Participants: This prospective cohort study included initially healthy women from the Nurses' Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020). Exposures: Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). Main Outcomes and Measures: The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors. Results: The final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals. Conclusions and Relevance: In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Associations of healthy dietary patterns with mortality among people with prediabetes.

PURPOSE: To examine the associations of healthy dietary patterns with cardiometabolic biomarkers and all-cause mortality among individuals with prediabetes. METHODS: This cohort study included 8363 adults with prediabetes from the National Health and Nutrition Examination Survey 1999-2014. Healthy dietary patterns including Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), Dietary Approaches to Stop Hypertension score (DASH), and Healthy Eating Index-2015 (HEI-2015) were calculated based on 24-h dietary recall data. Mortality status was obtained by linkage to National Death Index records. Cardiometabolic biomarkers, including blood glucose, insulin, HbA1c, C-reactive protein (CRP), and lipids, were measured at recruitment. RESULTS: During 61,991 person-years of follow-up, 991 deaths occurred. Comparing the extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.65 (0.49, 0.85) for AHEI-2010 (P-trend = 0.002), 0.68 (0.50, 0.92) for AMED (P-trend = 0.004), 0.72 (0.53, 0.98) for DASH (P-trend = 0.03), and 0.78 (0.58, 1.05) for HEI-2015 (P-trend = 0.08). Besides, the HRs (95% CIs) for all-cause mortality per 20-percentile increment in scores were 0.78 (0.67, 0.90) for AHEI-2010 (P = 0.001), 0.73 (0.62, 0.86) for AMED (P < 0.001), 0.84 (0.69, 1.02) for DASH (P = 0.08), and 0.86 (0.74, 1.00) for HEI-2015 (P = 0.04). In addition, higher dietary scores were associated with favorable blood glucose, insulin, HOMA-IR, blood lipids, and CRP (all P-trend < 0.05). The high-density lipoprotein cholesterol and CRP explained 1.53-9.21% of the associations between dietary patterns and all-cause mortality (P < 0.05). CONCLUSIONS: Diets with higher AHEI-2010, AMED, DASH, and HEI-2015 were associated with improved cardiometabolic factors and lower all-cause mortality among individuals with prediabetes. These findings suggest that multiple healthy dietary patterns instead of a one-size-fits-all diet plan might be beneficial and acceptable for individuals with prediabetes.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.

OBJECTIVE: Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. RESEARCH DESIGN AND METHODS: This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.

Evaluation of Sleep Habits and Disturbances Among US Adults, 2017-2020.

Importance: Unhealthy sleep behaviors and sleep disturbances are associated with higher risk of multiple diseases and mortality. The current profiles of sleep habits and disturbances, particularly the differences between workdays and free days, are unknown in the contemporary US. Objective: To comprehensively evaluate sleep habits on workdays and free days and the prevalence of sleep disturbances among US adults. Design, Setting, and Participants: This study is a cross-sectional analysis of US nationally representative data from the National Health and Nutrition Examination Survey (2017-2020) among adults aged 20 years or older. Data analysis was performed from February to May 2022. Main Outcomes and Measures: The main outcomes were means and/or distributions of sleep habits, including sleep duration and sleep-wake timing on workdays and free days, sleep debt (ie, the difference between sleep duration on free days and mean weekly sleep duration), and social jet lag (ie, the difference between the midpoint between sleep and wake time on workdays and free days). Prevalence of trouble sleeping (ie, participants told a doctor or other health professional that they have trouble sleeping) and daytime sleepiness (ie, self-reported feeling of being overly sleepy during the day ≥5 times per month) were also determined. Results: A total of 9004 individuals (mean [SE] age, 48.3 [0.53] years; 4635 women [51.9%]; 3158 non-Hispanic White [62.8%]) were included in the current study. The mean sleep duration was 7.59 hours (95% CI, 7.54 to 7.64 hours) on workdays and 8.24 hours (95% CI, 8.17 to 8.31 hours) on free days (difference, 0.65 hour). The mean sleep and wake times were at 11:02 pm (95% CI, 10:57 pm to 11:17 pm) and 6:41 am (95% CI, 6:36 am to 6:45 am), respectively, on workdays and 11:25 pm (95% CI, 11:21 pm to 11:35 pm) and 7:41 am (95% CI, 7:37 am to 7:46 am), respectively, on free days (differences, 0.23 hour for sleep time and 1.00 hour for wake time). On workdays, 23.1% (95% CI, 21.3% to 24.9%) of adults slept less than 7 hours and 25.4% (95% CI, 24.1% to 26.6%) went to sleep at midnight or later; the corresponding percentages changed to 12.9% (95% CI, 11.6% to 14.1%) and 40.9% (95% CI, 38.4% to 43.5%), respectively, on free days. Furthermore, the mean sleep debt was 0.73 hours (95% CI, 0.68 to 0.77 hours), and mean social jet lag was 1.10 hours (95% CI, 1.05 to 1.15 hours); 30.5% (95% CI, 26.8% to 33.3%) of adults experienced 1 hour or more of sleep debt, and 46.5% (95% CI, 42.6% to 50.3%) experienced 1 hour or more of social jet lag. The prevalence of trouble sleeping was 29.8% (95% CI, 28.2% to 31.5%), and that of daytime sleepiness was 27.2% (95% CI, 25.0% to 29.5%). Conclusions and Relevance: In 2017 to 2020, US adults showed variability in sleep habits between workdays and free days, with longer sleep duration and later sleep-wake phases on free days, and high percentages of US adults experienced long-term sleep deprivation, chronic social jet lag, and frequent sleep disturbances. These findings provide evidence to further investigate potential approaches to optimize overall US sleep health.

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects.

Background: Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive. Objective: To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults. Methods: This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001-2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality. Results: A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults (r s = 0.088, P < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29-0.85) and 0.75 (95% CI: 0.60-0.92), respectively. Each 1 µg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62-0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81-0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses. Conclusion: Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.

Associations of birth weight and later life lifestyle factors with risk of cardiovascular disease in the USA: A prospective cohort study.

Background: Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear. Methods: We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986-2016), 52,380 women from the Nurses' Health Study (NHS, 1980-2018), and 85,350 women from the Nurses' Health Study II (NHS II, 1991-2017) in the USA who reported birth weight and updated data on adult body weight, smoking status, physical activity, and diet every 2-4 years. Incident cases of CVD, defined as a combined endpoint of fatal and nonfatal coronary heart disease (CHD) and stroke, were self-reported and confirmed by physicians through reviewing medical records. Findings: During 4,370,051 person-years of follow-up, 16,244 incident CVD cases were documented, including 12,126 CHD and 4118 stroke cases. Cox proportional hazards regression models revealed an increased risk of CHD during adulthood across categories of decreasing birth weight in all cohorts (all P for linear trend <0.001). Additionally, we found an additive interaction between decreasing birth weight and unhealthy lifestyles on the risk of CHD among women, with a pooled relative excess risk due to interaction of 0.06 (95% CI: 0.04-0.08). The attributable proportions of the joint effect were 23.0% (95% CI: 11.0-36.0%) for decreasing birth weight alone, 67.0% (95% CI: 58.0-75.0%) for unhealthy lifestyle alone, and 11.0% (95% CI: 5.0-17.0%) for their additive interaction. Lower birth weight was associated with a greater stroke risk only among women, which was independent of later-life lifestyle factors. Interpretation: Lower birth weight may interact synergistically with unhealthy lifestyle factors in adulthood to further increase the risk of CHD among women. Funding: The National Institutes of Health grants.

Plasma Transthyretin Levels and Risk of Type 2 Diabetes Mellitus and Impaired Glucose Regulation in a Chinese Population.

Plasma transthyretin may be engaged in glucose regulation. We aimed to investigate the association between plasma transthyretin levels and the risk of newly diagnosed T2DM and impaired glucose regulation (IGR) in a Chinese population. We conducted a case-control study including 1244 newly diagnosed T2DM patients, 837 newly diagnosed IGR patients, and 1244 individuals with normal glucose tolerance (NGT) matched by sex and age. Multivariate logistic regression analysis was utilized to estimate the independent association of plasma transthyretin concentrations with the risk of T2DM and IGR. Plasma transthyretin concentrations were significantly higher in T2DM and IGR patients compared with control subjects (p < 0.005). After multiple adjustment and comparison with the lowest quartile of plasma transthyretin concentrations, the odds ratios (95% confidence intervals) of T2DM and IGR in the highest quartile were 2.22 (1.66, 2.98) and 2.29 (1.72, 3.05), respectively. Plasma transthyretin concentrations also showed a great performance in predicting the risk of T2DM (AUC: 0.76). Moreover, a potential nonlinear trend was observed. Our results demonstrated that higher plasma transthyretin concentrations, especially more than 290 mg/L, were associated with an increased risk of T2DM and IGR. Further studies are warranted to confirm our findings and elucidate the potential mechanisms.

Vitamin D status, genetic factors, and risks of cardiovascular disease among individuals with type 2 diabetes: a prospective study.

BACKGROUND: The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. OBJECTIVES: We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. METHODS: This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. RESULTS: The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D.

Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes: Results From NHANES.

OBJECTIVE: Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that ß-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D. RESEARCH DESIGN AND METHODS: This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum ß-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of ß-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum ß-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels. CONCLUSIONS: Higher concentrations of serum ß-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum ß-carotene concentrations in individuals with T2D.