Regular Mobile Phone Use and Incident Cardiovascular Diseases: Mediating Effects of Sleep Patterns, Psychological Distress, and Neuroticism.

BACKGROUND: The relationship between mobile phone use and incident cardiovascular disease (CVD) is uncertain. We aimed to examine the association of regular mobile phone use with incident CVD and explore the mediating effects of sleep and mental health. METHODS: A total of 444,027 individuals from the UK Biobank without a history of CVD were included. Regular mobile phone use was defined as at least 1 call per week. Weekly mobile phone usage time was self-reported as the average time of calls per week over the previous 3 months. The primary outcome was incident CVD. The secondary outcomes included each component of CVD and increased carotid intima-media thickness (CIMT). We applied Cox proportional hazard models to assess the association between mobile phone use and incident CVD, and mediation analyses to investigate the role of sleep patterns, psychologic distress, and neuroticism. RESULTS: In a median follow-up period of 12.3 years, 56,181 individuals developed incident CVD. Compared with nonregular mobile phone users, regular mobile phone users had a significantly higher risk of incident CVD (hazard ratio 1.04, 95% confidence interval 1.02-1.06) and increased CIMT (odds ratio 1.11, 95% CI 1.04-1.18). Among regular mobile phone users, weekly mobile phone usage time was positively associated with the risk of incident CVD, especially in current smokers (P for interaction = 0.001) and diabetic individuals (P for interaction = 0.037). Of the relationship between weekly mobile phone usage time and incident CVD, 5.11% was mediated by sleep patterns, 11.5% by psychological distress, and 2.25% by neuroticism. CONCLUSIONS: Weekly mobile phone usage time was positively associated with incident CVD risk, which was partly explained by poor sleep, psychologic distress, and neuroticism.

Enhanced prediction of atrial fibrillation risk using proteomic markers: a comparative analysis with clinical and polygenic risk scores.

BACKGROUND: Proteomic biomarkers have shown promise in predicting various cardiovascular conditions, but their utility in assessing the risk of atrial fibrillation (AF) remains unclear. This study aimed to develop and validate a protein-based risk score for predicting incident AF and to compare its predictive performance with traditional clinical risk factors and polygenic risk scores in a large cohort from the UK Biobank. METHODS: We analysed data from 36 129 white British individuals without prior AF, assessing 2923 plasma proteins using the Olink Explore 3072 assay. The cohort was divided into a training set (70%) and a test set (30%) to develop and validate a protein risk score for AF. We compared the predictive performance of this score with the HARMS2-AF risk model and a polygenic risk score. RESULTS: Over an average follow-up of 11.8 years, 2450 incident AF cases were identified. A 47-protein risk score was developed, with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) being the most significant predictor. In the test set, the protein risk score (per SD increment, HR 1.94; 95% CI 1.83 to 2.05) and NT-proBNP alone (HR 1.80; 95% CI 1.70 to 1.91) demonstrated superior predictive performance (C-statistic: 0.802 and 0.785, respectively) compared with HARMS2-AF and polygenic risk scores (C-statistic: 0.751 and 0.748, respectively). CONCLUSIONS: A protein-based risk score, particularly incorporating NT-proBNP, offers superior predictive value for AF risk over traditional clinical and polygenic risk scores, highlighting the potential for proteomic data in AF risk stratification.

Sweetened beverages and atrial fibrillation in people with prediabetes or diabetes.

AIM: To assess the association of intake of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new-onset atrial fibrillation (AF) in people with prediabetes or diabetes. METHODS: A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24-hour dietary recalls from 2009 to 2012. The study outcome was new-onset AF. RESULTS: During a median follow-up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04-1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02-1.14) were linearly and positively associated with new-onset AF, while NJ intake was not significantly associated with new-onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93-1.08). Accordingly, compared with non-consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11-1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05-1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83-0.99) lower risk of new-onset AF, while replacing SSBs with ASBs was not significantly associated with new-onset AF (adjusted HR = 0.97; 95% CI: 0.89-1.06). CONCLUSIONS: Both the intake of SSBs and ASBs were linearly and positively associated with new-onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF.

Association of Quantity and Diversity of Different Types of Fruit Intake with New-Onset Kidney Stones.

SCOPE: This study aims to assess the association between intake of different types of fruit (citrus, pomes, tropical fruits, berries, gourds, drupes, dried fruits, and other fruits), the intake diversity of fruit types, and risk of new-onset kidney stones in general population. METHODS AND RESULTS: A total of 205 896 participants with at least one completed 24-h dietary recall from the UK Biobank are included. During a median follow-up of 11.6 years, 2074 cases of kidney stones are documented. Compared with nonconsumers, participants with higher intake of citrus (50-<100 g day-1; hazards ratio [HR] = 0.78; 95% confidence interval [CI], 0.66-0.91; ≥100 g day-1; HR = 0.75; 95%CI, 0.63-0.89), pomes (≥100 g day-1; HR = 0.86; 95%CI, 0.77-0.96), or tropical fruits (50-<100 g day-1; HR = 0.86; 95%CI, 0.75-0.99; ≥100 g day-1; HR = 0.88; 95%CI, 0.79-0.99) have a lower risk of new-onset kidney stones. However, there is no significant association of intake of berries, gourds, drupes, dried fruits, and other fruits with kidney stones. A higher fruit variety score is significantly associated with a lower risk of new-onset kidney stones (per 1-score increment, HR = 0.86; 95%CI, 0.81-0.91). CONCLUSIONS: Higher intake of citruses (≥50 g day-1), pomes (≥100 g day-1), and tropical fruits (≥50 g day-1), as well as increasing diversity of intake of these three fruits, are associated with a lower risk of new-onset kidney stones.

Association of accelerometer-derived "weekend warrior" moderate to vigorous physical activity, chronic kidney disease and acute kidney injury.

OBJECTIVE: To examine the relationship between an accelerometer-derived "weekend warrior" pattern, characterized by achieving the most moderate to vigorous physical activity (MVPA) over 1-2 days, as opposed to more evenly distributed patterns, with risk of chronic kidney disease (CKD) and acute kidney injury (AKI). METHODS: 77,977 participants without prior kidney diseases and with usable accelerometer data (collected between 2013 and 2015) were included from the UK Biobank. Three physical activity patterns were compared: active weekend warrior pattern (achieving ≥150 min MVPA per week and accumulating ≥50 % of total MVPA in 1-2 days), active regular pattern (achieving ≥150 min MVPA but not meeting active weekend warrior criteria per week), and inactive pattern (<150 min MVPA per week). The study outcomes included incident CKD and AKI, ascertained through self-report data and data linkage with primary care, hospital admissions, and death registry records. RESULTS: During a median follow-up of 6.8 years, 1324 participants developed CKD and 1515 developed AKI. In multivariable-adjusted models, when compared with inactive participants, individuals with active weekend warrior pattern (CKD: hazard ratio [HR], 0.79, 95 % confidence interval [CI], 0.69-0.89; AKI: HR, 0.70, 95 %CI, 0.62-0.79) and those with active regular pattern (CKD: HR, 0.81, 95 %CI, 0.69-0.95; AKI: HR, 0.79, 95 %CI, 0.68-0.91) exhibited a similar and significantly lower risk of incident CKD and AKI. Similar findings were observed at the median threshold of ≥230.4 min of MVPA per week. CONCLUSION: Concentrated MVPA within 1 to 2 days is as effective as distributed ones in decreasing the risk of renal outcomes.

Inverse association between lung function and nonalcoholic fatty liver disease: An observational and mendelian randomization study.

BACKGROUND AND AIM: The association between lung function with non-alcoholic fatty liver disease (NAFLD) in the general population remains unknown. We aimed to examine the association between lung function and NAFLD among the general population in an observational and Mendelian randomization (MR) study. METHODS AND RESULTS: 340, 253 participants without prior liver diseases were included from the UK Biobank. Of these, 30,397 participants had liver proton density fat fraction (PDFF) measurements by magnetic resonance image (MRI). Lung function parameters included forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). The primary outcome was the presence of NAFLD, defined as a PDFF greater than 5.5%. The secondary outcome included incident severe NAFLD and severe liver diseases (including liver cirrhosis, liver failure, hepatocellular carcinoma and liver-related death), defined by the International Classification of Disease codes with different data sources. During a media follow-up duration of 9.3 years, 7335 (24.1%) the presence of NAFLD cases were documented. There was an inverse association of FEV1 (% predicted) (Per SD increment, adjusted OR = 0.91, 95%CI: 0.88-0.94) and FVC (% predicted) (Per SD increment, adjusted OR = 0.90, 95%CI: 0.87-0.92) with the presence of NAFLD. Similar results were found for incident severe NAFLD, severe liver disease, liver cirrhosis, liver failure and liver-related death. MR analyses showed that the genetically predicted FEV1 (adjusted OR = 0.63, 95%CI: 0.46-0.87) and FVC (adjusted OR = 0.69, 95%CI: 0.51-0.95) were both inversely associated with the presence of NAFLD. CONCLUSIONS: There was an inverse causal relationship between lung function and NAFLD in the general population.

Association Between Cognitive Function and Risk of Chronic Kidney Disease: A Longitudinal Cohort and Mendelian Randomization Study.

OBJECTIVE: To investigate the causal dose-response association between cognitive function and the risk of chronic kidney disease (CKD) by a longitudinal cohort and mendelian randomization study. METHODS: The longitudinal cohort study included 396,600 participants without prior dementia and CKD from the UK Biobank. Cognitive function (including prospective memory, numeric memory, visuospatial memory, reaction time, and reasoning ability) was assessed by computerized touchscreen tests. Global cognitive function was defined as a composite score of those specific cognitive domains. A 2-stage mendelian randomization analysis was conducted with 12,979 cases of CKD and 379,424 controls. Genetically predicted global cognitive function was instrumented with 91 confirmed genome-wide significant variants. The study outcome was new-onset CKD. The study was conducted from March 13, 2006, to September 30, 2021. RESULTS: During a median follow-up of 12.5 years, new-onset CKD developed in 13,090 participants. Per 1 SD score increments in reaction time (adjusted hazard ratio [HR], 0.97; 95% CI, 0.95 to 0.99), reasoning ability (adjusted HR, 0.91; 95% CI, 0.88 to 0.94), and global cognitive function (adjusted HR, 0.96; 95% CI, 0.95 to 0.98) were associated with a significantly lower risk of new-onset CKD. Compared with an incorrect answer in the prospective memory test, a correct answer was associated with a lower risk of new-onset CKD (adjusted HR, 0.82; 95% CI, 0.76 to 0.88). Mendelian randomization analyses found that per 1 SD score increments in genetically predicted global cognitive function resulted in a significantly (7%; 95% CI, 2% to 12%) lower risk of new-onset CKD. CONCLUSION: A better cognitive function is causally associated with a lower risk of CKD in participants without prior dementia.

The level of discomfort during the use of different circuits of the mechanical ventilator.

Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV. Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale. Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy. Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.

Large-Scale Proteomics Improve Prediction of Chronic Kidney Disease in People With Diabetes.

OBJECTIVE: To develop and validate a protein risk score for predicting chronic kidney disease (CKD) in patients with diabetes and compare its predictive performance with a validated clinical risk model (CKD Prediction Consortium [CKD-PC]) and CKD polygenic risk score. RESEARCH DESIGN AND METHODS: This cohort study included 2,094 patients with diabetes who had proteomics and genetic information and no history of CKD at baseline from the UK Biobank Pharma Proteomics Project. Based on nearly 3,000 plasma proteins, a CKD protein risk score including 11 proteins was constructed in the training set (including 1,047 participants; 117 CKD events). RESULTS: The median follow-up duration was 12.1 years. In the test set (including 1,047 participants; 112 CKD events), the CKD protein risk score was positively associated with incident CKD (per SD increment; hazard ratio 1.78; 95% CI 1.44, 2.20). Compared with the basic model (age + sex + race, C-index, 0.627; 95% CI 0.578, 0.675), the CKD protein risk score (C-index increase 0.122; 95% CI 0.071, 0.177), and the CKD-PC risk factors (C-index increase 0.175; 95% CI 0.126, 0.217) significantly improved the prediction performance of incident CKD, but the CKD polygenic risk score (C-index increase 0.007; 95% CI -0.016, 0.025) had no significant improvement. Adding the CKD protein risk score into the CKD-PC risk factors had the largest C-index of 0.825 (C-index from 0.802 to 0.825; difference 0.023; 95% CI 0.006, 0.044), and significantly improved the continuous 10-year net reclassification (0.199; 95% CI 0.059, 0.299) and 10-year integrated discrimination index (0.041; 95% CI 0.007, 0.083). CONCLUSIONS: Adding the CKD protein risk score to a validated clinical risk model significantly improved the discrimination and reclassification of CKD risk in patients with diabetes.

Association between longitudinal changes in body composition and the risk of kidney outcomes in participants with overweight/obesity and type 2 diabetes mellitus.

AIMS: To assess the relationship of longitudinal changes in fat mass (FM), lean mass (LM) and waist circumference (WC) with incident kidney outcomes in people with overweight/obesity and type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total of 3927 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial were included. The primary outcome was kidney outcomes, defined as a decrease in eGFR of at least 40% from baseline at follow-up visit, or end-stage kidney disease. RESULTS: During a median follow-up of 8.0 years, 450 kidney outcomes were documented after the first 1 year. In the intensive lifestyle intervention (ILI) group, reductions in FM (per 10% decrease, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69-0.94) and WC (per 10% decrease, adjusted HR 0.72, 95% CI 0.59-0.88) from baseline to 1-year follow-up were significantly associated with a lower risk of kidney outcomes. The change in LM was not significantly associated with risk of kidney outcomes (per 10% decrease, adjusted HR 0.78, 95% CI 0.58-1.06). In the diabetes support and education group (control group), no significant association was found between changes in body composition and kidney outcomes. Similar results were observed for the 4-year changes in body composition. CONCLUSIONS: In this post hoc analysis of the Look AHEAD trial, longitudinal declines in FM and WC were associated with a lower risk of kidney outcomes in the ILI group in participants with overweight/obesity and T2DM.

Association between lung function and risk of microvascular diseases in patients with diabetes: A prospective cohort and Mendelian randomization study.

BACKGROUND AND AIMS: To investigate causal relationships of lung function with risks microvascular diseases among participants with diabetes, type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM), respectively, in prospective and Mendelian randomization (MR) study. METHODS AND RESULTS: 14,617 participants with diabetes and without microvascular diseases at baseline from the UK Biobank were included in the prospective analysis. Of these, 13,421 had T2DM and 1196 had T1DM. The linear MR analyses were conducted in the UK Biobank with 6838 cases of microvascular diseases and 10,755 controls. Lung function measurements included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The study outcome was microvascular diseases, a composite outcome including chronic kidney diseases, retinopathy and peripheral neuropathy. During a median follow-up of 12.1 years, 2668 new-onset microvascular diseases were recorded. FVC (%predicted) was inversely associated with the risk of new-onset microvascular diseases in participants with diabetes (Per SD increment, adjusted HR = 0.86; 95%CI:0.83-0.89), T2DM (Per SD increment, adjusted HR = 0.86; 95%CI:0.82-0.90) and T1DM (Per SD increment, adjusted HR = 0.87; 95%CI: 0.79-0.97), respectively. Similar results were found for FEV1 (%predicted). In MR analyses, genetically predicted FVC (adjusted RR = 0.55, 95%CI:0.39-0.77) and FEV1 (adjusted RR = 0.48, 95%CI:0.28-0.83) were both inversely associated with microvascular diseases in participants with T1DM. No significant association was found in those with T2DM. Similar findings were found for each component of microvascular diseases. CONCLUSION: There was a causal inverse association between lung function and risks of microvascular diseases in participants with T1DM, but not in those with T2DM.

Tea Consumption, Milk or Sweeteners Addition, Genetic Variation in Caffeine Metabolism, and Incident Venous Thromboembolism.

OBJECTIVE: The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association. METHODS: A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism. RESULTS: During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76-0.94), only milk (HR: 0.86; 95% CI: 0.80-0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81-0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75-1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659). CONCLUSION: Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche.

Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into neural progenitor-like (NPC-like), oligodendrocyte-progenitor-like (OPC-like), astrocyte-like (AC-like) and mesenchymal like (MES-like) states, it does not capture the spatial localization of these tumor cell states. Spatial transcriptomics empowers the study of the spatial organization of different cell types and tumor cell states and allows for the selection of regions of interest to investigate region-specific and cell-type-specific pathways. Here, we obtained paired 10x Chromium single-nuclei RNA-sequencing (snRNA-seq) and 10x Visium spatial transcriptomics data from three GBM patients to interrogate the GBM microenvironment. Integration of the snRNA-seq and spatial transcriptomics data reveals patterns of segregation of tumor cell states. For instance, OPC-like tumor and NPC-like tumor significantly segregate in two of the three samples. Our differentially expressed gene and pathway analyses uncovered significant pathways in functionally relevant niches. Specifically, perinecrotic regions were more immunosuppressive than the endogenous GBM microenvironment, and perivascular regions were more pro-inflammatory. Our gradient analysis suggests that OPC-like tumor cells tend to reside in areas closer to the tumor vasculature compared to tumor necrosis, which may reflect increased oxygen requirements for OPC-like cells. In summary, we characterized the localization of cell types and tumor cell states, the gene expression patterns, and pathways in different niches within the GBM microenvironment. Our results provide further evidence of the segregation of tumor cell states and highlight the immunosuppressive nature of the necrotic and perinecrotic niches in GBM.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy, older Chinese individuals.

Background: The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain. Aims: To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy, older Chinese individuals. Methods: The study included a total of 3106 participants capable of completing repeated cognitive function tests. Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption. Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified. Results: The median follow-up duration was 5.9 years. There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores, with an inflection point of 0.68 mg/day (95% confidence interval (CI): 0.56 to 0.80) and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake. Before the inflection point, thiamine intake was not significantly associated with cognitive decline. Beyond the inflection point, each unit increase in thiamine intake (mg/day) was associated with a significant decrease of 4.24 (95% CI: 2.22 to 6.27) points in the global score and 0.49 (95% CI: 0.23 to 0.76) standard units in the composite score within 5 years. A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension, obesity and those who were non-smokers (all p<0.05). Conclusions: This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy, older Chinese individuals, with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Association of accelerometer-measured physical activity and its change with progression to chronic kidney disease in adults with type 2 diabetes and overweight/obesity.

OBJECTIVE: To examine the long-term association of objectively measured moderate-to-vigorous physical activity (MVPA) and its longitudinal changes with progression to chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and overweight/obesity. METHODS: This study included 1746 participants in the Look AHEAD trial with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2. MVPA was measured at baseline, year 1, year 4 and year 8 using an RT3 accelerometer. The outcome was progression to CKD, defined as eGFR<60 mL/min per 1.73 m2 with a drop of ≥30% or end-stage kidney disease. Cox hazards models were fitted to examine the association between MVPA and outcomes. RESULTS: Over a median follow-up of 12.0 years, 567 participants experienced progression to CKD. Overall, there was a linear inverse association of cumulative average total MVPA (per 100 min/week higher amount, HR: 0.91; 95% CI: 0.86 to 0.96) and MVPA accumulated in bouts of ≥10 min (per 100 minutes/week higher amount, HR: 0.81; 95% CI: 0.72 to 0.91) with progression to CKD. Moreover, an increase in total MVPA from baseline to year 4 (the fourth quartile, ≥63.2 min/week) was associated with a 33% lower risk of progression to CKD compared with the largest MVPA reduction (the first quartile, <-198.3 min/week). A lower risk of progression to CKD was also observed for increases in MVPA accumulated in bouts of both <10 min and ≥10 min. CONCLUSIONS: Longer MVPA time and increases in MVPA was associated with a reduced risk of progression to CKD in adults with overweight/obesity and T2D.

L-shaped association between dietary zinc intake and cognitive decline in Chinese older people.

BACKGROUND AND OBJECTIVE: The prospective association between dietary zinc (Zn) intake and cognitive decline remains uncertain. We aimed to assess the relationship of dietary Zn intake with the risk of cognitive decline in the Chinese older people, and examine the possible effect modifiers on this association. METHODS: A total of 3,106 older Chinese adults aged 55 years or older from China Health and Nutrition Survey were included. Dietary nutrients intake information was collected by combined 24-h dietary recalls with weighing food inventory. The cognitive decline was defined as the 5-year decline rate in global and composite cognitive scores, based on a subset of items from the Telephone Interview for Cognitive Status-modified. RESULTS: The median follow-up duration was 5.9 years. There was an L-shaped association between dietary Zn intake and the 5-year decline rates in global and composite cognitive scores, with an inflection point at 8.8 mg/day of dietary Zn. For the composite cognitive scores, compared with the first quantile (<7.9 mg/day) of dietary Zn intake, quantiles 2-6 (≥7.9 mg/day) had a significantly slower cognitive decline rate (ß: -0.24; 95% confidence interval: -0.40 to -0.07). Similar results were found for the global cognitive scores. Moreover, the inverse association between dietary Zn intake and cognitive decline in composite cognitive scores was significantly stronger in those with lower levels of physical activity (P-interactions = 0.041). CONCLUSION: Dietary Zn intake was negatively associated with cognitive decline in the older people. Maintaining appropriate dietary Zn levels may prevent cognitive decline.

Relationship of dietary intake of food folate and synthetic folic acid intake from fortified foods with all-cause mortality in individuals with chronic kidney disease.

OBJECTIVE: To evaluate the association of the dietary intake of food folate (natural folate) and synthetic folic acid intake from fortified foods with the risk of all-cause mortality and end-stage kidney disease (ESKD) among the chronic kidney disease (CKD) population in regions with folic acid fortification. METHODS: 4028 individuals with established CKD in Chronic Renal Insufficiency Cohort (CRIC) were included. Diet was assessed using a validated diet history questionnaire at the baseline, year 2, and year 4, and nutrient intake, including food folate and folic acid from fortified foods, was estimated using the National Nutrient Database. The outcomes were all-cause mortality and ESKD. The results for all-cause mortality were further validated using the data from National Health and Nutrition Examination Surveys (NHANES). RESULTS: During a median follow-up of 11.1 years, 1155 deaths and 938 ESKD cases occurred. Compared with the first quartile of food folate intake, the third (HR: 0.74; 95% CI: 0.62, 0.90) and fourth (HR: 0.79; 95% CI: 0.63, 0.98) quartiles had a lower risk of all-cause mortality. Nevertheless, there was no significant association of synthetic folic acid intake from fortified foods with all-cause mortality. Similar results were observed for ESKD. Consistently, in NHANES, food folate intake and serum 5-methyltetrahydrofolate, but not folic acid intake, were inversely associated with all-cause mortality, while serum unmetabolized folic acid was positively associated with all-cause mortality in CKD participants. CONCLUSIONS: Higher intake of dietary natural folate, but not synthetic folic acid intake from fortified foods, was associated with lower risks of all-cause mortality and ESKD among CKD participants.

Social isolation, loneliness, and the risk of incident acute kidney injury in middle-aged and older adults: A prospective cohort study.

OBJECTIVE: The relationships of social isolation and loneliness with acute kidney injury (AKI) risk remained uncertain. We aimed to investigate the associations of social isolation and loneliness with incident AKI. METHODS: 450,868 participants without prior AKI were included from the UK Biobank. The social isolation index was constructed based on living alone, social contact, and participation in social activities. Loneliness was assessed by asking about "Do you often feel lonely?". The study outcome was incident AKI. RESULTS: During a median follow-up of 12.0 years, 18,679 (4.1%) participants developed AKI, including 18,428 participants ascertained by hospital admission records with a median duration of hospitalization of 3 (25th-75th, 1-8) days. The hazard ratio for incident AKI for social isolation compared with no social isolation was 1.50 (95% CI: 1.44-1.55) after adjusting for age and race (minimally adjusted), and was 1.10 (95% CI: 1.06-1.14) after further adjusting for socioeconomic factors, health behaviors, biological and health-related factors, psychologic factors, and loneliness (fully adjusted). The minimally adjusted and fully adjusted hazard ratios for incident AKI for loneliness compared with no loneliness was 1.57 (95% CI: 1.52-1.62), and 1.10 (95% CI: 1.06-1.15), respectively. In the fully adjusted models, the highest risk of AKI was found in those with both social isolation and loneliness. Living alone and less social contact, rather than less participation in social activities, were significantly associated with a higher risk of incident AKI. CONCLUSIONS: Both social isolation and loneliness were independently and significantly associated with a higher risk of incident AKI.

Serum 25-Hydroxyvitamin D, Vitamin D Receptor, and Vitamin-D-Binding Protein Gene Polymorphisms and Risk of Dementia Among Older Adults With Prediabetes.

BACKGROUND: The association between vitamin D and dementia risk in those with prediabetes remains uncertain. We aimed to evaluate the association of serum 25-hydroxyvitamin D (25OHD) with incident dementia among older adults with prediabetes, and examine whether apolipoprotein E (APOE) genotypes, vitamin D receptor (VDR), and vitamin-D-binding protein (VDBP) gene polymorphisms may modify this association. METHODS: A total of 34 237 participants aged ≥60 with prediabetes (HbA1c <6.5% and ≥5.7%) and without dementia at baseline were included from the UK Biobank. Serum 25-hydroxyvitamin D (25OHD) was measured using chemiluminescent immunoassay method. The primary outcome was incident all-cause dementia. Secondary outcomes included incident Alzheimer's disease (AD) and vascular dementia, respectively. The VDR and VDBP gene polymorphisms included single nucleotide polymorphisms of rs7975232, rs1544410, rs2228570, rs731236, and rs7041, rs4588, respectively. RESULTS: During a median follow-up of 11.8 years, 941 (2.7%) participants developed incident all-cause dementia. Overall, serum 25OHD was inversely associated with all-cause dementia (per standard deviation increment, adjusted hazard ratio: 0.82; 95% confidence interval: 0.75, 0.89). Similar trends were found for incident AD and vascular dementia. Furthermore, there was a stronger inverse relationship between serum 25OHD and all-cause dementia among VDR rs7975232 C allele noncarriers (p-interaction < 0.05). However, APOE Ɛ4, other VDR, and VDBP gene polymorphisms did not significantly modify the relation of serum 25OHD with incident all-cause dementia (all p-interactions >.05). CONCLUSIONS: There was an inverse association between serum 25OHD and incident dementia among older adults with prediabetes, especially in VDR rs7975232 AA allele carriers.