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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. [ABSTRACT FROM AUTHOR] more...

We aimed to assess the association between exposure to various air pollutants, individually or jointly, and incident kidney stones, and examine whether genetic susceptibility for kidney stones may modify this association. 453,977 participants without prior kidney stones from the UK Biobank were included. Annual mean concentrations of PM2.5, PM2.5–10, PM10, NO2, and NOx were estimated with a land use regression model. A weighted air pollution score was constructed that incorporates the five pollutants mentioned above. A genetic risk score (GRS) was calculated based on 20 single-nucleotide polymorphisms associated with kidney stones. The primary outcome was incident kidney stones. During a median follow-up of 11.9 years, 5,375 kidney stones were recorded. The adjusted HRs (95%CI) of incident kidney stones were 1.04 (1.01–1.07), 1.02 (1.00–1.05), 1.03 (1.01–1.06), 1.05 (1.02–1.08), and 1.04 (1.01–1.07), for per standard deviation (SD) increment in PM2.5 (SD:1.06 μg/m3), PM2.5–10 (SD:0.90 μg/m3), PM10 (SD:1.90 μg/m3), NO2 (SD:7.63 μg/m3), and NOx (SD: 15.63 μg/m3), respectively. Moreover, there was a significantly linear association between the air pollution score and incident kidney stones (per SD increment: HR, 1.05, 95%CI: 1.02–1.08), especially in those without diabetes (vs. participants with diabetes; P-interaction = 0.037). In addition, the association between air pollution and kidney stones was statistically significant only in participants within intermediate-high kidney stone GRS, but not in those with low GRS kidney stone, though the interaction was not significant (P-interaction = 0.385). In conclusion, exposure to air pollution was associated with a higher risk of incident kidney stones, calling for the need to improve air quality. [ABSTRACT FROM AUTHOR] more...

It remains unclear whether inflammatory bowel disease is associated with long-term risk of chronic kidney disease (CKD) and acute kidney injury (AKI) in the general population. A total of 417,302 participants, including 2,940 patients with ulcerative colitis and 1,261 patients with Crohn's disease, without previous CKD and AKI at baseline (2006–2010) from the UK Biobank were included. The study outcomes included incident CKD and AKI, ascertained by self-report data and data linkage with primary care, hospital admissions, and death registry records. Analysis was conducted in 2022. During a median follow-up of 12.5 years, 13,564 and 14,331 participants developed CKD and AKI, respectively. Compared with the hazard ratio for non-inflammatory bowel diseases, the hazard ratios for CKD and AKI related to inflammatory bowel diseases were 1.57 (95% CI=1.37, 1.79) and 1.96 (95% CI=1.74, 2.20) after adjustments for age, sex, and race and were 1.32 (95% CI=1.15, 1.51) and 1.70 (95% CI=1.51, 1.91) after further adjustments for biological, behavioral, and socioeconomic factors in addition to mental health and self-rated health. Similar results were found for patients with Crohn's disease (adjusted hazard ratio=1.38 (95% CI=1.09, 1.75) for CKD and 1.62 [95% CI=1.30, 2.02] for AKI) and those with ulcerative colitis (adjusted hazard ratio=1.29 (95% CI=1.09, 1.51) for CKD and 1.71 [95% CI=1.49, 1.97] for AKI) in the fully adjusted models. Genetic risks of kidney diseases did not significantly affect the association of inflammatory bowel disease with incident CKD and AKI (both p -interactions>0.05). The association between inflammatory bowel disease and the risk of incident CKD (p -interaction=0.010) and AKI (p -interaction<0.001) were stronger in younger participants than in older participants. Inflammatory bowel disease was associated with higher risks for CKD and AKI, independent of genetic risks of kidney diseases. [ABSTRACT FROM AUTHOR] more...

Background: The relationship of glucosamine use with incident dementia in the older population remains uncertain. We aimed to evaluate the longitudinal association between habitual glucosamine supplement and the risk of cause-specific dementia and examine the possible effect modifiers on this association. Methods: The study included 214,945 participants over the age of 60 who had available information on glucosamine use and did not have dementia at baseline in the UK Biobank. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. The primary outcome was incident vascular dementia, incident Alzheimer's disease, and incident frontotemporal dementia, respectively. Results: Over a median follow-up duration of 12 years, 1039, 1774, and 122 participants developed vascular dementia, Alzheimer's disease, and frontotemporal dementia, respectively. Overall, habitual glucosamine use was significantly associated with a lower risk of incident vascular dementia (adjusted HR, 0.82; 95%CI, 0.70–0.96), but not significantly associated with incident Alzheimer's disease (adjusted HR, 1.02; 95%CI, 0.92–1.14) and incident frontotemporal dementia (adjusted HR, 0.95; 95%CI, 0.63–1.43). Moreover, the inverse association between habitual glucosamine use and incident vascular dementia was more pronounced in participants with concomitant supplement of calcium (P-interaction = 0.011), and those without concomitant supplement of zinc (P-interaction = 0.018). However, APOE ε4 dosage and baseline cognitive function did not significantly modify the relationships of glucosamine use with incident vascular dementia or Alzheimer's disease (All P-interactions > 0.05). Conclusions: Regardless of APOE genotypes and baseline cognitive function, habitual glucosamine use was significantly inversely associated with incident vascular dementia in the older population. [ABSTRACT FROM AUTHOR] more...

We aimed to investigate the prospective association of individual and combined sleep behaviors and mental health (psychological distress and neuroticism) with incident irritable bowel syndrome (IBS). A total of 302,839 participants without prior IBS in the UK Biobank were enrolled. A healthy sleep score was created according to five sleep factors and defined the low-risk groups as follows: sleep 7–8 h/day, early chronotype, never/rarely insomnia, no snoring, and no frequent excessive daytime sleepiness. Psychological distress and neuroticism were ascertained using the Patient Health Questionnaire and the Eysenck Personality Questionnaire-Revised Short Form, respectively. The primary outcome was incident IBS, based on self-report or linkage to death register and/or primary care and/or hospital admission data. During a median follow-up of 12.0 years, 5574 participants developed IBS. Overall, low-risk sleep behaviors and a healthy sleep score (per one point increment, HR, 0.81, 95%CI, 0.79–0.83) were associated with a lower risk of incident IBS, 29.4 %–32.4 % of which was mediated by mental health. Psychological distress (per one point increment, HR, 1.16, 95%CI, 1.14–1.17) and neuroticism (HR, 1.11, 95%CI, 1.10–1.12) were positively associated with incident IBS, and healthy sleep scores mediated 8.3 %–9.7 % of the association. Moreover, participants with lowest healthy sleep score/highest mental health score and higher genetic risk of IBS showed the highest risk of incident IBS. Sleep behaviors and mental health were assessed by self-reported questionnaires. Healthy sleep scores and low psychological distress/neuroticism were associated with a lower risk of IBS, regardless of genetic predisposition. • Healthy sleep was associated with a lower risk of incident IBS. • Mental health mediated 29.4 %–32.4 % of the association between sleep and IBS. • Psychological distress and neuroticism were related to a higher risk of incident IBS. • Sleep mediated 8.3 %–9.7 % of the association between mental health and IBS. • Participants with poor sleep/mental health and high IBS genetic risk had highest IBS risk. [ABSTRACT FROM AUTHOR] more...

Introduction: We aimed to investigate the relations of handgrip strength, walking pace and the combination of handgrip strength and walking pace with incident hypertension, and to explore whether this association was modified by the genetic risk of hypertension. Methods: 214 214 participants without prior hypertension in the UK Biobank were included. Handgrip strength was assessed by dynamometer. Walking pace was self‐defined as slow, average, or brisk. The study outcome was incident hypertension. A genetic risk score for hypertension was generated using a Bayesian approach applied to meta‐analyzed summary statistics GWAS data. Results: Over a median follow‐up of 11.9 years, 13 344 (6.2%) participants developed incident hypertension. When handgrip strength was assessed as sex‐specific quartiles, compared with those with the lowest handgrip strength (quartile 1), the adjusted HRs (95% CI) of incident hypertension in quartile 2, quartile 3, and quartile 4 were 0.80 (0.69, 0.93), 0.74 (0.64, 0.86), and 0.72 (0.61, 0.84), respectively. Compared with those with slow walking pace, participants with average (HR, 0.52; 95% CI: 0.40, 0.67) or brisk (HR, 0.43; 95% CI: 0.32, 0.56) walking pace had significantly lower risks of hypertension. Moreover, compared with those with both lower handgrip strength (quartile 1) and slow walking pace, the lowest risk of incident hypertension was observed in participants with both high handgrip strength (quartiles 2–4) and fast (average or brisk) walking pace (HR, 0.36; 95% CI: 0.25, 0.52). Genetic risks of hypertension did not significantly modify the association (p‐interaction = 0.300). Conclusion: Both higher handgrip strength and faster walking pace were significantly associated with a lower risk of incident hypertension, independent of genetic risks of hypertension. [ABSTRACT FROM AUTHOR] more...

Objective: The prospective relation of vitamin D status with the risk of chronic kidney diseases (CKD) remains uncertain. We aimed to examine the association of serum 25-hydroxyvitamin D (25OHD) with new-onset CKD in participants with and without diabetes at baseline and examine the potential modifications by genetic susceptibility on the association.Research Design and Methods: Included were 348,243 adults from the UK Biobank without prior CKD at baseline. Serum 25OHD concentrations were measured by chemiluminescent immunoassay method. Genetic risk score of CKD was calculated by 263 single nucleotide polymorphisms, which showed significant associations with estimated glomerular filtration rate. The primary outcome was new-onset CKD.Results: During a median follow-up duration of 12.1 years, 9,344 new-onset CKD were documented. Overall, there was a significant inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes (per SD increment, adjusted hazard ratio [HR] 0.91; 95% CI 0.86-0.96), but not in those without diabetes (per SD increment, adjusted HR 0.98; 95% CI 0.96-1.01; P-interaction between serum 25OHD and diabetes = 0.004). Accordingly, among participants with diabetes, compared with those baseline serum 25OHD <25 nmol/L, a significantly lower risk of new-onset CKD was found in those with 25OHD ≥50 nmol/L (adjusted HR 0.77; 95% CI 0.67-0.89). Moreover, the genetic risk of CKD did not significantly modify the association between baseline serum 25OHD and new-onset CKD among participants with diabetes (P-interaction = 0.127).Conclusions: There was an inverse association between baseline serum 25OHD and new-onset CKD in participants with diabetes. The inverse association was not found in participants without diabetes. [ABSTRACT FROM AUTHOR] more...

Objectives: The association between habitual glucosamine use and incident gout has not been examined in previous studies. We aimed to evaluate the association of habitual use of glucosamine with the risk of gout in general population. Methods: A total of 436,594 participants (55.4% female) without prior gout at baseline who completed a questionnaire on supplementation use, which included glucosamine, in the UK Biobank were enrolled. Incident gout was recorded from self-report, death register, primary care, and hospital admission data. Results: At baseline, 53,433 (22.1%) females and 30,685 (15.8%) males reported habitual glucosamine use. During a median follow-up period of 12.1 years, 1718 (0.7%) females and 5685 (2.9%) males developed gout. After multivariable adjustment for major risk factors, glucosamine use was associated with a significantly lower risk of incident gout in females (hazard ratio [HR], 0.81, 95% confidence interval [CI], 0.71–0.92), but not in males (HR, 1.05, 95% CI, 0.97–1.13), compared with non-use (P-interaction < 0.001). Among females, the inverse association between glucosamine use and gout was stronger in participants with diuretics use (HR, 0.64, 95% CI, 0.50–0.81) than those without diuretics use (HR, 0.89, 95% CI, 0.77–1.03) (P-interaction = 0.015). Moreover, gout genetic risk scores did not significantly modify the association between glucosamine use and the risk of incident gout in males (P-interaction = 0.548) or females (P-interaction = 0.183). Conclusions: Habitual glucosamine use to relieve osteoarthritis pain was related to lower risk of gout in females, but not in males. Highlights: Glucosamine use was associated with lower risk of incident gout in females. The inverse association between glucosamine use and gout was stronger in females with diuretics use. Gout genetic risk scores did not significantly modify the association. [ABSTRACT FROM AUTHOR] more...

The modifying effect of prediabetic status on the association of social isolation and loneliness with the risk of type 2 diabetes mellitus (T2DM) remains uncertain. We aimed to explore whether prediabetic status modifies the association of social isolation and loneliness with incident T2DM. 358,951 participants with random blood glucose < 11.1 mmol/l, hemoglobin A1c < 6.5 % and without diagnosis of diabetes from the UK Biobank were included. Prediabetes was defined by hemoglobin A1c level at 5.7–6.4 %. Social isolation and loneliness were assessed using self-reported questionnaires. The study outcome was incident T2DM. During a median follow-up of 12.5 years, 13,213 (3.7 %) incident T2DM cases were documented. Social isolation and loneliness in subjects with normoglycemia (adjusted HR [95 %CI]: social isolation: 1.14 [1.07;1.23]; loneliness: 1.33 [1.20;1.47]) were more strongly associated with increased risk of T2DM than in those with prediabetes (adjusted HR [95 %CI]: social isolation: 0.97 [0.91;1.03]; loneliness: 1.04 [0.95;1.13]) (Both P for interaction < 0.001). Among individuals with prediabetes, alcoholic consumption (30.9 %), household income (23.3 %), healthy sleep (17.1 %), loneliness (14.9 %), and physical activity (12.6 %) mediated most of the variance in the association between social isolation and incident T2DM, while body mass index (17.9 %) and healthy sleep (17.6 %) mediated most of the variance in the association between loneliness and incident T2DM. Social isolation and loneliness were independently associated with a higher risk of T2DM among individuals without prediabetes. Among those with prediabetes, the association of social isolation and loneliness with incident T2DM were mainly mediated by some socioeconomic and lifestyle factors. [ABSTRACT FROM AUTHOR] more...

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. 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. 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. Both social isolation and loneliness were independently and significantly associated with a higher risk of incident AKI. • Social isolation was significantly associated with a higher risk of incident AKI. • Loneliness was significantly associated with a higher risk of incident AKI. • The highest risk of AKI was found in those with both social isolation and loneliness. [ABSTRACT FROM AUTHOR] more...

This study aimed to investigate the relationship of residential green and blue spaces with incident nonalcoholic fatty liver disease (NAFLD), and explore the potential mediation effects of air pollutants and modification effect of genetic susceptibility. 411,200 UK Biobank participants without prior liver diseases were included. Land use data were used to estimate residential green and blue spaces (land coverage percentage) at 300 m and 1000 m buffer. The study outcome was incident NAFLD, ascertained through linkage to hospital admissions and death registry records. 5198 NAFLD cases were documented after a median follow-up of 12.5 years. Green and blue spaces were inversely associated with the hazard of NAFLD: per standard deviation (SD) increment of green space coverage at 300 m (SD: 14.5 %; HR, 0.88, 95 %CI, 0.86–0.91) and 1000 m (SD: 14.1 %; HR, 0.88, 95 %CI, 0.86–0.91) buffer, and blue space coverage at 300 m (SD: 1.0 %; HR,0.95, 95 %CI, 0.93–0.98) and 1000 m (SD: 1.2 %; HR,0.96, 95 %CI, 0.93–0.99) buffer were related with a 4–12 % reduction of NAFLD incidence. The beneficial effects of approximately 25–52 % of green space exposure and about 5–35 % of blue space exposure on NAFLD incidence were mediated by the reduction of PM 2.5 , NO 2 and NO x (All P indirect effect <0.05). Moreover, genetic susceptibility of NAFLD did not modify the relationship of green and blue spaces with NAFLD incidence. Residential green and blue spaces were inversely related to NAFLD incidence. These results suggest that green and blue spaces are modifiable factors that may help prevent NAFLD, and therefore, can be considered as a novel environmental strategy to promote liver health at the community level, rather than only at the individual level. • Green/blue space was inversely associated with incident nonalcoholic fatty liver disease (NAFLD). • The benefit of green/blue space was partly mediated by reduced air pollutants. • People exposed to greater green/blue spaces with low genetic risk of NAFLD had lowest NAFLD risk. [ABSTRACT FROM AUTHOR] more...

The relationship of air pollutants and residential exposure to greenspace with severe liver disease remains inconclusive. Our objective was to assess the relationship of joint exposure to air pollutants, residential exposure to greenspaces with new-onset severe liver disease. We included 427,697 participants without prior liver diseases from UK Biobank. A weighted air pollution score was calculated based on PM 2.5 , PM 10 , PM 2.5–10 , NO 2 , and NO X. The percentage of land coverage by residential greenspaces was estimated using land use data. The primary outcome was new-onset severe liver disease, defined as a composite outcome including hospitalization or death due to compensated or decompensated liver cirrhosis, liver failure, and hepatocellular carcinoma. During a median follow-up of 12.0 years, 4572 participants developed severe liver disease. A higher air pollution score was significantly associated with an increased risk of new-onset severe liver disease (per SD increment; adjusted hazard ratio [HR],1.07; 95% confidence interval [CI],1.04–1.10). Moreover, residential greenspace coverage was inversely associated with new-onset severe liver disease (per SD increment; adjusted HR, 0.95; 95% CI,0.92–0.98). Genetic risks of liver cirrhosis did not significantly modify the associations (both P -interactions >0.05). However, we observed a stronger positive association between air pollution scores and new-onset severe liver disease in individuals with higher fibrosis-4 (FIB-4) scores, lower residential greenspaces, hypertension, and smokers (all P -interactions <0.05). Similarly, a more pronounced inverse association between residential exposure to greenspaces and new-onset severe liver disease was found in smokers and individuals with higher FIB-4 scores (both P -interactions<0.05). Our findings suggest a positive association between air pollution scores and the risk of new-onset severe liver disease, while residential greenspaces show an inverse association. These results underscore the importance of maintaining high exposure to green space and reducing air pollution to prevent serious liver disease. • Air pollution score was positively associated with severe liver disease. • Residential greenspace was negatively associated with severe liver disease. • Residential greenspace may reduce effects of air pollution on severe liver disease. • Low FIB-4, no hypertension, non-smoking prevents air pollution-linked liver diseases. [ABSTRACT FROM AUTHOR] more...

The association of a healthy lifestyle and the American Heart Association (AHA) Life's Essential 8 (LE8) score with the risk of new-onset nonalcoholic fatty liver disease (NAFLD) remains uncertain. We aimed to explore the associations between a healthy lifestyle and higher LE8 scores with new-onset severe NAFLD in the general population. 266,645 participants without prior liver diseases were included from the UK Biobank. A healthy lifestyle was determined based on body mass index, smoking, alcohol consumption, physical activity, sleep duration, and diet. LE8 score was generated from 8 metrics according to the AHA cardiovascular health (CVH) advisory, varying from 0 to 100 scores. The primary study outcome was new-onset severe NAFLD. The study outcomes were ascertained by hospital inpatient data, cancer registry, and death register records. During a median follow-up of 11.9 years, 2284(0.9 %) participants developed severe NAFLD. Compared with those with a poor lifestyle, participants with intermediate (HR, 0.60; 95%CI: 0.55–0.67), or ideal (HR, 0.20; 95%CI: 0.15–0.27) lifestyles had a significantly lower risk of new-onset severe NAFLD. Compared to the low CVH group (LE8 scores: 0–49), the moderate (scores:50–79) (HR, 0.43; 95%CI: 0.39–0.48) and high CVH (scores:80–100) (HR, 0.10; 95%CI: 0.07–0.14) group had a significantly lower risk of new-onset severe NAFLD. Accordingly, adhering to a healthy lifestyle and attaining a high CVH in all individuals could prevent 66.8 % (95%CI: 58.5–75.1 %) and 77.3 % (95%CI:70.4–84.2 %) of severe NAFLD, respectively. Genetic risks of NAFLD did not modify these associations. A favorable lifestyle and a higher LE8 score were significantly associated with a lower risk of new-onset severe NAFLD, independent of genetic risks of NAFLD. [Display omitted] • The association of a healthy lifestyle and the LE8 scores with the risk of new-onset severe NAFLD remains uncertain. • A healthy lifestyle and a higher LE8 score were associated with a lower risk of new-onset severe NAFLD, regardless of genetic risks. • A healthier lifestyle and a higher LE8 score would prevent approximately 66.8% and 77.3% of new-onset severe NAFLD, respectively. [ABSTRACT FROM AUTHOR] more...

Whether diabetes and genetic susceptibility of kidney diseases modifies the relationship between ultra-processed foods (UPF) consumption and incident chronic kidney disease (CKD) remains uncertain. We aimed to investigate the association between UPF consumption and new-onset CKD in participants with and without diabetes, and explore whether genetic risks of kidney diseases may modify the association. 153,985 participants who were free of CKD at baseline and provided 24-h dietary recalls in the UK Biobank were included. UPF was defined according to the NOVA classification. The energy contribution of UPF was calculated by dividing the energy intake of UPF by the total energy intake. The study outcome was new-onset CKD, ascertained by self-report data and data linkage with primary care, hospital admissions, and death registry records. During a median follow-up of 12.1 years, 4,058 participants developed new-onset CKD. There was a significant positive association between UPF consumption and new-onset CKD in total participants (per 10% increment, adjusted hazard ratio (HR) 1.04; 95% confidence interval (CI) [1.01;1.06]. The positive association between UPF consumption and risk of new-onset CKD was significantly stronger in participants with diabetes (per 10% increment, adjusted HR 1.11 [1.05;1.17]) than in those without diabetes (per 10% increment, adjusted HR 1.03 [1.00;1.05]; P -interaction = 0.005). Genetic risks of kidney diseases did not significantly modify the positive association in those with or without diabetes (all P -interactions > 0.05). There was a significantly stronger positive association between UPF consumption and new-onset CKD in participants with diabetes compared with those without diabetes. [ABSTRACT FROM AUTHOR] more...

The relation of regular ibuprofen or paracetamol use with the risk of type 2 diabetes (T2DM) remained undetermined. We aimed to evaluate the prospective association between regular ibuprofen or paracetamol use and incidence of T2DM. This cohort included 372,843 participants with available data of ibuprofen, paracetamol use and without diabetes at baseline from the UK Biobank. The primary outcome was incident T2DM. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of T2DM. During a median of 12.1 years' follow-up, 11,527 (3.1%) participants developed T2DM. Overall, participants with regular use of paracetamol showed a significantly higher risk of incident T2DM (adjusted HR, 1.25; 95%CI: 1.19,1.31), compared with non-users. Moreover, a stronger positive association of paracetamol use with incident T2DM was found among those aged <60 years (vs. ≥60 years, P -interaction =0.008), free of cardiovascular diseases (CVD) (vs. CVD patients, P -interaction =0.01), and without the use of anti-hypertensive drugs (vs. users, P -interaction =0.016) at baseline. However, there was no significant association between regular use of ibuprofen (users vs. non-users; adjusted HR, 1.05; 95%CI: 0.99,1.12) and incident T2DM. More importantly, genetic risks of T2DM did not significantly modify the relations of ibuprofen, or paracetamol use with incident T2DM (Both P -interactions >0.05). Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of incident T2DM among middle aged UK adults. Our current findings highlight the need for greater consideration in the clinical selection of paracetamol or ibuprofen. [ABSTRACT FROM AUTHOR] more...

Although the possible efficacy and adverse effects of paracetamol and ibuprofen on dementia are of global clinical and public health importance, to date, the relationship of the use of paracetamol and ibuprofen with incident dementia remains uncertain. We aimed to assess the prospective association of regular use of ibuprofen and paracetamol with new-onset dementia in an older population. This study included 212,968 participants from the UK Biobank, aged ≥60 years, with available data of ibuprofen, paracetamol use and without dementia at baseline. The primary outcome was new-onset all-cause dementia. The secondary outcomes included new-onset Alzheimer's disease and new-onset vascular dementia. During a median follow-up of 12.3 years, 6407 (3.0%) participants developed new-onset all-cause dementia. Participants who regularly used paracetamol had a significantly higher risk of new-onset all-cause dementia (adjusted HR, 1.18; 95%CI: 1.10–1.26), compared with non-users. However, there was no significant association between regular use of ibuprofen and new-onset all-cause dementia (users vs. non-users; adjusted HR, 1.06; 95%CI: 0.97–1.16). Furthermore, APOE ε4 dosage and genetic risk scores (GRS) of Alzheimer's disease calculated by 25 single nucleotide polymorphisms did not significantly modify the relationship of regular use of paracetamol and ibuprofen with new-onset all-cause dementia (Both P -interactions >0.05). Similar results were found in the propensity score analysis. Similar findings were also observed for new-onset Alzheimer's disease and new-onset vascular dementia. Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of new-onset dementia in the old population, regardless of genetic risks of dementia. [ABSTRACT FROM AUTHOR] more...

To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic risk of kidney stones on this association. 473,225 participants free of kidney stones at baseline from the UK Biobank were included. Total sedentary time was calculated as the sum of the duration of TV-watching, driving, and non-occupational computer using. The primary outcome was new-onset kidney stones. During a median follow-up of 12.0 years, 5528 cases of kidney stones were documented. All major sedentary behaviors and total sedentary time were significantly positively related to the risk of kidney stones (All P for trend<0.05). Participants with total sedentary time ≥ 3.5 h/day had a significantly higher risk of new-onset kidney stones (vs. <3.5 h/day [tertile 1]; HR, 1.18; 95%CI,1.10–1.27). Compared with non-users, participants who regularly used glucosamine had a significantly lower risk of new-onset kidney stones in those with total sedentary time < 3.5 h/day (HR, 0.72; 95%CI,0.59–0.86), but not in those with total sedentary time ≥ 3.5 h/day (HR, 0.99; 95%CI,0.91–1.08; P -interaction = 0.001). Among participants with total sedentary time < 3.5 h/day, there was a dose-response relationship of glucosamine use with new-onset kidney stones (P for trend<0.001). Genetic risks of kidney stones did not significantly modify the association. TV-watching, driving and non-occupational computer using were all positively associated with the risk of new-onset kidney stones. Glucosamine use was associated with a lower risk of new-onset kidney stones in participants with total sedentary time < 3.5 h/day, following a dose-response relationship. • Sedentary behavior was positively associated with kidney stone risk. • Glucosamine use reduced the risk of kidney stones in people with less sedentary time. • Genetic risks of kidney stones did not significantly modify the association. [ABSTRACT FROM AUTHOR] more...

The association between sleep behaviors and gout risk remains uncertain. We aimed to evaluate the relationship of sleep patterns based on a combination of five major sleep behaviors with the risk of new-onset gout, and to explore whether genetic risks of gout may modify this association in the general population. 403,630 participants without gout at baseline in UK Biobank were included. A healthy sleep score was created by combining five major sleep behaviors, including chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Genetic risk score for gout was calculated based on 13 single nucleotide polymorphisms (SNPs) with independently significant genome-wide association with gout. The primary outcome was new-onset gout. During a median follow-up duration of 12.0 years, 4270 (1.1%) participants developed new-onset gout. Compared to participants with poor sleep patterns (0 ≤ healthy sleep score ≤ 1), those with healthy sleep patterns (4 ≤ healthy sleep score ≤ 5) had a significantly lower risk of new-onset gout (HR, 0.79; 95% CI: 0.70–0.91). Moreover, the significantly lower risk of new-onset gout associated with healthy sleep patterns were mainly found in those with low (HR, 0.68; 95%CI: 0.53–0.88), or intermediate genetic risks of gout (HR, 0.78; 95%CI: 0.62–0.99), but not in participants with high genetic risks of gout (HR, 0.95; 95%CI: 0.77–1.17) (P for interaction =0.043). Among the general population, a healthy sleep pattern was associated with a significant lower of new-onset gout risk, especially in those with lower genetic risks of gout. • Sleep health is multidimensional and various sleep behaviors are typically clustered. • A healthy sleep pattern was associated with a lower risk of new-onset gout. • This association was stronger in those with lower genetic risks of gout. [ABSTRACT FROM AUTHOR] more...

We aimed to evaluate the association of coffee consumption with different additives, including milk and/or sweetener (sugar and/or artificial sweetener), and different coffee types, with new-onset acute kidney injury (AKI), and examine the modifying effects of genetic variation in caffeine metabolism. 194 324 participants without AKI at baseline in the UK Biobank were included. The study outcome was new-onset AKI. During a median follow-up of 11·6 years, 5864 participants developed new-onset AKI. Compared with coffee non-consumers, a significantly lower risk of new-onset AKI was found in coffee consumers adding neither milk nor sugar to coffee (hazard ratio (HR), 0·86; 95 % CI, 0·78, 0·94) and adding only milk to coffee (HR,0·83; 95 % CI, 0·78, 0·89), but not in coffee consumers adding only sweetener (HR,1·14; 95 % CI, 0·99, 1·31) and both milk and sweetener to coffee (HR,0·96; 95 % CI, 0·89, 1·03). Moreover, there was a U-shaped association of coffee consumption with new-onset AKI, with the lowest risk at 2-3 drinks/d, in unsweetened coffee (no additives or milk only to coffee), but no association was found in sweetened coffee (sweetener only or both milk and sweetener to coffee). Genetic variation in caffeine metabolism did not significantly modify the association. A similar U-shaped association was found for instant, ground and decaffeinated coffee consumption in unsweetened coffee consumers, but not in sweetened coffee consumers. In conclusion, moderate consumption (2-3 drinks/d) of unsweetened coffee with or without milk was associated with a lower risk of new-onset AKI, irrespective of coffee type and genetic variation in caffeine metabolism. more...

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., Competing Interests: None declared., (Thieme. All rights reserved.) more...

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.) more...

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., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.) more...

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., (© 2024 John Wiley & Sons Ltd.) more...

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 HARMS 2 -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 HARMS 2 -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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.) more...

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.) more...

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.) more...

Background: The liver effects of concentrated vs. more evenly distributed moderate-to-vigorous physical activity (MVPA) patterns remain unclear. We aimed to examine the association of accelerometer-measured MVPA and different MVPA patterns with liver outcomes., Methods: Eighty-eight thousand six hundred fifty-six participants without prior liver diseases from UK Biobank were included. MVPA was measured by a wrist-worn accelerometer. Based on the guideline-based threshold (≥ 150 min/week), MVPA patterns were defined as inactive (< 150 min/week), active weekend warrior (WW; ≥ 150 min/week with ≥ 50% of total MVPA achieved within 1-2 days), and regularly active (≥ 150 min/week but not active WW) patterns. The primary outcome was incident nonalcoholic fatty liver disease (NAFLD)., Results: During a median follow-up of 6.8 years, 562 participants developed NAFLD. Overall, there was a nonlinear inverse association of total MVPA with incident NAFLD (P for nonlinearity = 0.009): the risk of NAFLD rapidly decreased with the increment of MVPA (per 100 min/week increment: HR = 0.68; 95%CI, 0.57-0.81) when MVPA < 208 min/week, while moderately declined (HR = 0.91; 95%CI, 0.84-0.99) when MVPA ≥ 208 min/week. For MVPA patterns, compared with inactive group, both active WW (HR = 0.55, 95%CI, 0.44-0.67) and active regular (HR = 0.49, 95%CI, 0.38-0.63) group were associated with a similar lower risk of NAFLD. Similar results were observed for each secondary outcome, including incident severe liver diseases, incident liver cirrhosis, and liver magnetic resonance imaging-based liver steatosis and fibrosis., Conclusions: Regardless of whether MVPA was concentrated within 1 to 2 days or spread over most days of the week, more MVPA was associated with a lower risk of incident liver outcomes, including NAFLD, liver cirrhosis, liver steatosis, and fibrosis, to MVPA more evenly distributed., (© 2024. The Author(s).) more...

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., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.) more...

Background:  The association between dietary manganese (Mn) intake and the risk of venous thromboembolism (VTE) remains unknown. We aimed to investigate the associations of dietary Mn intake with incident VTE, and the underlying mediating roles of obesity markers (body mass index [BMI] and waist circumference), hemorheological parameters (red cell distribution width [RDW], platelet count [PLT], and mean platelet volume [MPV]), and inflammatory biomarkers (C-reactive protein [CRP] and white blood cell count [WBC]) in this association., Methods:  A total of 202,507 adults from the UK Biobank with complete dietary data and without VTE at baseline were included. Dietary information was collected by the online 24-hour diet recall questionnaires (Oxford WebQ). The primary outcome was incident VTE, a composite of incident deep vein thrombosis (DVT) and pulmonary embolism (PE)., Results:  During a median follow-up of 11.6 years, 4,750 participants developed incident VTE. Overall, there were significantly inverse relationships of dietary Mn intake with incident VTE (per 1 mg/day increment; adjusted hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.90-0.95), incident DVT (per 1 mg/day increment; adjusted HR: 0.93; 95% CI: 0. 90-0.96), and incident PE (per 1 mg/day increment; adjusted HR: 0.91; 95% CI: 0.88-0.95). BMI, waist circumference, RDW, CRP, and WBC significantly mediated the association between dietary Mn intake and incident VTE, with the mediated proportions of 36.0, 36.5, 4.2, 4.3, and 1.6%, respectively. However, MPV and PLT did not significantly mediate the association., Conclusion:  Our study shows that dietary Mn intake was inversely associated with incident VTE. The inverse association was mainly mediated by obesity, followed by inflammatory biomarkers and RDW. Our findings are just hypothesis-generating, and further confirmation of our findings in more studies is essential., Competing Interests: None declared., (Thieme. All rights reserved.) more...

Background: The individual and combined relations of handgrip strength and walking pace with the risk of chronic kidney disease (CKD) remain uncertain. We aimed to investigate the relationship of handgrip strength and/or walking pace with incident CKD, using data from the large-scale, observational UK Biobank., Methods: A total of 417 504 participants free of prior kidney diseases were included from UK Biobank. Handgrip strength was assessed by dynamometer. The walking pace was self-reported as slow, average, or brisk. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CKD., Results: The average age of the study population was 56.3 (SD, 8.1) years. 192 012 (46.0%) of the participants were male. The mean handgrip strength was 23.5 (SD, 6.2) and 40.0 (SD, 8.8) kg for females and males, respectively. Over a median follow-up duration of 12.1 years, 11 064 (2.7%) participants developed incident CKD. Handgrip strength was significantly inversely associated with the risk of incident CKD in both males and females (both P for trend <0.001). When handgrip strength was assessed as sex-specific quartiles, compared with those in the first quartile, the adjusted HRs (95% CI) of incident CKD in participants in the second, third and fourth quartiles were 0.84 (0.79, 0.89), 0.76 (0.71, 0.81) and 0.72 (0.67, 0.77), respectively. Compared with those with slow walking pace, participants with average (HR, 0.64; 95% CI: 0.60-0.68) or brisk (HR, 0.53; 95% CI: 0.49-0.57) walking pace had significantly lower risks of incident CKD. Compared with those with both lower handgrip strength (the first quartile) and slow walking pace, the lowest risk of incident CKD was observed in participants with both higher handgrip strength (the 2-4 quartiles) and average or brisk walking pace (HR, 0.51; 95% CI: 0.46-0.55)., Conclusions: Handgrip strength and walking pace were significantly inversely associated with incident CKD in the general population., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.) more...

Background: The prospective associations of serum 25(OH)D, sun exposure time, and dietary vitamin D with risk of acute kidney injury (AKI) are unclear., Objectives: We aimed to evaluate the relations of serum 25(OH)D, sun exposure time, and dietary vitamin D intake with new-onset AKI and examine whether genetic susceptibility modified such associations., Methods: A total of 413,169 participants (mean age was 56.4 y, 47.2% were male) from UK Biobank without prior AKI were included. Sun exposure time was expressed as time spent outdoors. Genetic risk scores were calculated by 263 single nucleotide polymorphisms, which showed significant associations with the estimated glomerular filtration rate. The primary outcome was new-onset AKI. Cox proportional hazards models were used to estimate the HRs and (95% CIs)., Results: During a median follow-up duration of 12 y, 16,938 (4.1%) participates developed new-onset AKI. Compared with those with serum 25(OH)D <25 nmol/L, significantly lower risks of new-onset AKI were found between participants with 25(OH)D 25 to <50 nmol/L (adjusted HR: 0.76; 95% CI: 0.73, 0.80), and ≥50 nmol/L (adjusted HR: 0.69; 95% CI: 0.65, 0.72). Moreover, in summer, participants who spent ≥4 h outdoors per day (tertile 3) had a significantly lower risk of new-onset AKI (adjusted HR: 0.90; 95% CI: 0.86, 0.95) than those who spent <2 h outdoors per day (tertile 1). Similar results were found for time spent outdoors in winter. In addition, those in quintile 5 of dietary vitamin D intake showed a lower risk of new-onset AKI (≥4.2 μg/d, adjusted HR: 0.90; 95% CI: 0.82, 0.98) than those in quintile 1 (<1.0 μg/d). Genetic risks of kidney diseases did not significantly modify all the 3 above associations (all P-interactions >0.05)., Conclusions: Serum 25(OH)D concentrations, time spent outdoors, and dietary vitamin D intake were all inversely associated with new-onset AKI, independent of genetic risks for kidney diseases., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.) more...

Background: The independent and additive associations of walking pace and grip strength on dementia risk and the potential modifying effects of age, APOE phenotypes, and other dementia risk factors on the walking pace and dementia relationships demand further clarification. We aimed to investigate the independent and additive relationships of walking pace and handgrip strength on the risk of new-onset dementia and examine the potentially modifying effects of age, APOE phenotypes, lifestyle factors, and family history of dementia in the relationships., Methods: A total of 495,700 participants from the UK Biobank, who were free of dementia at baseline, were included in this study. Walking pace was self-defined as slow, average, or brisk. Handgrip strength was assessed by dynamometer and was divided into sex-specific quartiles. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. Other dementia risk factors, including education, physical activity, hypertension, depression, diabetes, and family history of dementia, were also collected. The primary outcome was new-onset all-cause dementia., Results: Over a median follow-up duration of 12.0 years, 3986 (0.8%) participants developed new-onset all-cause dementia. Compared with those with slow walking pace, participants with average (HR, 0.61; 95%CI: 0.55-0.68) or brisk (HR, 0.59; 95%CI: 0.52-0.67) walking pace had a significantly lower risk of new-onset all-cause dementia. Moreover, compared with those with both slow walking pace and lower handgrip strength (the first quartile), the lowest risk of new-onset all-cause dementia was observed in participants with both average or brisk walking pace and higher handgrip strength (the 2-4 quartiles) (HR, 0.45; 95%CI: 0.40-0.52). Notably, the negative relationship between walking pace and the risk of new-onset all-cause dementia was significantly reduced as APOE ε4 dosage increased (APOE ε4 dosages = 0 or 1: brisk vs. slow: HR, 0.55; 95%CI: 0.48-0.63; vs. APOE ε4 dosages = 2: brisk vs. slow: HR, 1.14; 95%CI: 0.77-1.68; P for interaction = 0.001) or age increased (< 58 [median]: brisk vs. slow: HR, 0.27; 95%CI: 0.18-0.41; vs. ≥ 58 years: brisk vs. slow: HR, 0.55; 95%CI: 0.48-0.63; P for interaction = 0.007)., Conclusions: Walking pace was inversely associated with new-onset dementia in the general population, especially in younger participants and those with lower APOE ε4 dosage. Participants with both faster walking pace and higher handgrip strength had the lowest risk of dementia, suggesting that maintaining both high handgrip strength and fast walking pace may be a more comprehensive strategy for preventing dementia risk., (© 2023. The Author(s).) more...

Background: To explore the relation of habitual fish oil use with the risk of chronic kidney diseases (CKD)., Methods: 408,023 participants (54.2% female) without prior CKD and with completed information regarding their consumption of major food groups and fish oil in the UK Biobank were enrolled. Fish oil use and dietary intakes were assessed by touch screen questionnaire and food frequency questionnaire, respectively. Incident CKD was recorded from hospital inpatient records., Results: At baseline, 128,843 (31.6%) participants reported taking fish oil supplements. During a median follow-up period of 12.0 years, a total of 10,782 (2.6%) participants developed CKD. With adjustments for important confounders, habitual fish oil use was associated with a significantly lower hazard of incident CKD (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.95), compared with non-use. Consistently, participants reporting ≥2 servings/week of oily fish (HR, 0.86; 95% CI, 0.79-0.94) and nonoily fish (HR, 0.86; 95% CI, 0.77-0.97) consumption had a lower hazard of incident CKD compared to those reporting no consumption ever. Additionally, among the 97,914 participants with data on plasma fatty acid, there were significant inverse relationships of plasma omega-3 polyunsaturated fatty acid (PUFA) (per SD increment, HR, 0.89, 95% CI, 0.84-0.94) and eicosatetraenoic acid (per SD increment, HR, 0.91, 95% CI, 0.87-0.96) with incident CKD., Conclusions: Habitual fish oil use was associated with a lower hazard of CKD, which was further confirmed by the consistent inverse relations between fish consumption and circulating omega-3 PUFA concentration with incident CKD. more...