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Introduction: Walking pace is associated with various health‐related outcomes. The aim of this study was to investigate the association between self‐reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). Methods: Self‐reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health‐related factors were used to estimate hazard ratios (HRs) and 95% CIs. Results: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow‐up of 12.5 (interquartile range: 11.6–13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable‐adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27–1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27–6.60). Conclusions: Self‐reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population‐based cohort study. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between sensory impairments and the risk of dementia is inconclusive. We aim to investigate the association of visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) with incident dementia. Methods: The UK Biobank study recruited more than 500,000 participants aged 40–69 years across the United Kingdom. Participants with available visual acuity (VA) measurements and speech-reception-threshold (SRT) information and free of dementia at the baseline assessment were included in the analysis. VI was defined as VA worse than 0.3 LogMAR units and HI were defined as an SRT of −5.5 dB or over. DSI was defined as the presence of both VI and HI. Incident dementia was identified through linked data to primary care or hospital admission records and death registries. Multivariable Cox proportional hazard regression models were used to examine the association of VI, HI, and DSI with incident dementia. Results: Among 113,511 participants (mean age: 56.8 ± 8.09 years, female: 54.4%), a total number of 1,135 (1.00%) cases of incident dementia were identified during a median follow up period of 11.1 years [interquartile range (IQR): 10.9–11.4 years]. The incidence of dementia showed significant differences among the non-sensory impairment (NSI) group, VI-only group, HI-only group, and DSI group (p < 0.001). After adjusting for demographic, lifestyle, health, and genetic factors, isolated VI (HR = 1.50, 95% CI : 1.06–2.12, p = 0.023), isolated HI (HR = 1.42, 95% CI :1.20–1.69, p < 0.001), and DSI (HR = 1.82, 95% CI : 1.10–3.00, p = 0.020) were independently associated with higher risks of incident dementia. Conclusions: Visual, hearing, and dual sensory impairments were associated with an increased risk of developing dementia, suggesting that visual and hearing impairments are modifiable risk factors that can be targeted to prevent dementia. [ABSTRACT FROM AUTHOR]

To investigate the precise association between BMI and waist circumference (WC) and diabetic complications, including retinopathy (DR), nephropathy (DN) and peripheral neuropathy (DPN). A multivariable-adjusted Cox proportional hazard model was used to evaluate the observed association from 30,541 UK Biobank participants with diabetes. A two-sample Mendelian randomization (MR) framework was applied to summary-level GWASs of BMI and WC comprising a total of 461,460 and 462,166 participants from UK Biobank to explore the potential causal association. Higher BMI and WC were associated with increased risks of DR, DN, and DPN (HR (95% CI), per-SD increase: BMI: DR 1.09 (1.04–1.13), DN 1.37 (1.33–1.41), DPN 1.27 (1.20–1.34); WC: DR 1.11 (1.07–1.16), DN 1.41 (1.36–1.46), DPN 1.38 (1.30–1.45)) in the UK Biobank cohort. Univariate MR indicated that increased BMI and WC were causal risk factors for these complications (OR (95% CI), per-SD increase: BMI: DR 1.33 (1.22–1.45), DN 1.74 (1.47–2.07), DPN 2.20 (1.67–2.90); WC: DR 1.43 (1.27–1.61), DN 2.03 (1.62–2.55), DPN 2.80 (1.99–3.92)), and the effect sizes remained significant after adjustment for glycated hemoglobin. Prospective observational and MR analyses provided evidence that high BMI and WC may represent potential causal risk factors for diabetic microvascular complications. Weight control might modify the risks of these complications independently of glycemic control and should be considered as a therapeutic recommendation. [ABSTRACT FROM AUTHOR]

Change-point detection in the context of recurrent-event is a valuable analysis tool for the identification of the intensity rate changes. It has been an interesting topic in many fields, such as medical studies, travel safety analysis, etc. If subgroups exist, clustering can be incorporated into the change-point detection to improve the quality of the results. This paper develops a new algorithm named Recurrent-K-means to detect the change-points of the intensity rates and identify clusters of objects with recurrent events. It also proposes a test-based method to perform a heuristic search in determining the number of underlying clusters. In this study, the objects are assumed to fall in several clusters while the objects in the same cluster share identical change-points. The event count for an object is assumed to be a non-homogeneous Poisson process with a piecewise-constant intensity function. The methodology estimates the change-point as well as the intensity rates before and after the change-point for each cluster. The methodology establishes a clustering analysis based on K-means algorithm but enhances the procedure to be model based. The simulation study shows that the methodology performs well in parameter estimation and determination of the number of clusters in different scenarios. The methodology is applied to the UK coal mining disaster data to show its possible role in shaping government regulations and improving coal industry safety. [ABSTRACT FROM AUTHOR]

Older adults have been markedly impacted by the coronavirus disease 19 (COVID-19) pandemic, and many reports have cited concerns regarding potential psychiatric sequelae of coronavirus disease (COVID-19), but the actual effects of psychotropics on the COVID-19 are unclear. In this study, multivariate logistic regression was used to evaluate associations between the prescription of psychotropics and the risk of SARS-CoV-2 infection, and COVID-19-related death among the participants who were tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) before October 18, 2021, in UK Biobank. The psychotropics included 18 types of medications. Among 168,173 participants who underwent testing for SARS-CoV-2 RNA, 30,577 (18.2%) were positive, and 14,284 (8.5%) participants used psychotropics. Among 30,577 participants who were infected with SARS-CoV-2, 1,181 (3.9%) were COVID-19-related deaths, and 2,542 (8.3%) participants used psychotropics. In multivariate logistic regression, psychotropics use was significantly associated with the risk of SARS-CoV-2 infection (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.88–0.98), and COVID-19-related death (OR, 0.78; 95% CI, 0.64–0.98). Interestingly, the use of diazepam was significantly associated with a 31% lower risk of SARS-CoV-2 infection (OR, 0.69; 95% CI, 0.53–0.88). The use of sertraline was significantly associated with a 89% lower risk of COVID-19-related death (OR, 0.11; 95% CI, 0.02–0.39). In conclusion, our findings suggested that the use of psychotropics was associated with a lower risk of SARS-CoV-2 infection and COVID-19-related deaths. [ABSTRACT FROM AUTHOR]

Concerns regarding adverse events associated with the use of acid suppressants have increased. However, the impact of proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) on the risk of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to estimate the risk of ASCVD in association with the use of PPIs and H2RAs. This prospective cohort study included participants without cardiovascular diseases or anti-hypertensive treatment at baseline (2006–2010) in the UK Biobank. The outcomes were ASCVD and each subtype (coronary artery disease, myocardial infarction, peripheral artery disease, and ischemic stroke). The association was estimated by Cox proportional-hazards models. Among 316,730 individuals (aged 50–88 years), during a median of 12.5 years of follow-up, we documented 13,503 (4.3%) incident ASCVD. Regular PPIs use was associated with a higher risk of ASCVD (HR: 1.16, 95% CI: 1.09–1.23) and every subtype of ASCVD. Among each type of PPIs, omeprazole (HR: 1.19, 95% CI: 1.11–1.28), lansoprazole (HR: 1.11, 95% CI: 1.02–1.22), and pantoprazole (HR: 1.40, 95% CI: 1.00–1.97) were associated with a higher risk of ASCVD. Stratification analysis showed that PPIs use was associated with a higher risk of ASCVD among individuals without indications of medications for PPIs. In addition, use of H2RAs was not related to the risk of ASCVD (HR: 0.97, 95% CI: 0.85–1.11). PPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs. [Display omitted] • Evidence of association between proton pump inhibitors (PPIs) and atherosclerotic cardiovascular disease (ASCVD) is lacking. • PPI use was related to a higher risk of ASCVD. • Histamine‐2 receptor antagonists (H2RAs) use was not related to the risk of ASCVD. • Effect of different types of PPIs on the risk of ASCVD was various. • Higher ASCVD risks were observed among PPI users without indications for medication. [ABSTRACT FROM AUTHOR]

Background: Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications., Methods and Results: There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association., Conclusions: Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

Objective: To investigate associations between different glycemic status and biological age indexed by retinal age gap., Methods: A total of 28,919 participants from the UK Biobank study with available glycemic status and qualified retinal imaging data were included in the present analysis. Glycemic status included type 2 diabetes mellitus (T2D) disease status and glycemic indicators of plasma glycated hemoglobin (HbA1c) and glucose. Retinal age gap was defined as the difference between the retina-predicted age and chronological age. Linear regression models estimated the association of different glycemic status with retinal age gap., Results: Prediabetes and T2D was significantly associated with higher retinal age gaps compared to normoglycemia (regression coefficient [β] = 0.25, 95% confidence interval [CI]: 0.11-0.40, P = 0.001; β = 1.06, 95% CI: 0.83-1.29, P < 0.001; respectively). Multi-variable linear regressions further found an increase of HbA1c was independently associated with higher retinal age gaps among all subjects or subjects without T2D. Significant positive associations were noted across the increasing HbA1c and glucose groups with retinal age gaps compared to the normal level group. These findings remained significant after excluding diabetic retinopathy., Conclusions: Dysglycemia was significantly associated with accelerated ageing indexed by retinal age gaps, highlighting the importance of maintaining glycemic status., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Plasma metabolomic profile is disturbed in dementia patients, but previous studies have discordant conclusions., Methods: Circulating metabolomic data of 110,655 people in the UK Biobank study were measured with nuclear magnetic resonance technique, and incident dementia records were obtained from national health registers. The associations between plasma metabolites and dementia were estimated using Cox proportional hazard models. The 10-fold cross-validation elastic net regression models selected metabolites that predicted incident dementia, and a 10-year prediction model for dementia was constructed by multivariable logistic regression. The predictive values of the conventional risk model, the metabolites model, and the combined model were discriminated by comparison of area under the receiver operating characteristic curves (AUCs). Net reclassification improvement (NRI) was used to estimate the change of reclassification ability when adding metabolites into the conventional prediction model., Results: Amongst 110,655 participants, the mean (standard deviation) age was 56.5 (8.1) years, and 51 186 (46.3%) were male. A total of 1439 (13.0%) developed dementia during a median follow-up of 12.2 years (interquartile range: 11.5-12.9 years). A total of 38 metabolites, including lipids and lipoproteins, ketone bodies, glycolysis-related metabolites, and amino acids, were found to be significantly associated with incident dementia. Adding selected metabolites (n=24) to the conventional dementia risk prediction model significantly improved the prediction for incident dementia (AUC: 0.824 versus 0.817, p =0.042) and reclassification ability (NRI = 4.97%, P = 0.009) for identifying high risk groups., Conclusions: Our analysis identified various metabolomic biomarkers which were significantly associated with incident dementia. Metabolomic profiles also provided opportunities for dementia risk reclassification. These findings may help explain the biological mechanisms underlying dementia and improve dementia prediction., (© 2022. The Author(s).)

Background: Dual sensory impairment is affecting over 10% of older adults worldwide. However, the long-term effect of dual sensory impairment (DSI) on the risk of mortality remains controversial. We aim to investigate the impact of single or/and dual sensory impairment on the risk of mortality in a large population-based sample of the adult in the UK with 14-years of follow-up., Methods: This population-based prospective cohort study included participants aged 40 and over with complete records of visual and hearing functions from the UK Biobank study. Measurements of visual and hearing functions were performed at baseline examinations between 2006 and 2010, and data on mortality was obtained by 2021. Dual sensory impairment was defined as concurrent visual and hearing impairments. Cox proportional hazards regression models were employed to evaluate the impact of sensory impairment (dual sensory impairment, single visual or hearing impairment) on the hazard of mortality., Results: Of the 113,563 participants included in this study, the mean age (standard deviation) was 56.8 (8.09) years, and 61,849 (54.5%) were female. At baseline measurements, there were 733 (0.65%) participants with dual sensory impairment, 2,973 (2.62%) participants with single visual impairment, and 13,560 (11.94%) with single hearing impairment. After a follow-up period of 14 years (mean duration of 11 years), 5,992 (5.28%) participants died from all causes. Compared with no sensory impairment, dual sensory impairment was significantly associated with an estimated 44% higher hazard of mortality (hazard ratio: 1.44 [95% confidence interval, 1.11-1.88], p = 0.007) after multiple adjustments., Conclusions: Individuals with dual sensory impairment were found to have an independently 44% higher hazard of mortality than those with neither sensory impairment. Timely intervention of sensory impairment and early prevention of its underlying causes should help to reduce the associated risk of mortality., (© 2022. The Author(s).)

Objective: Few studies have investigated the associations of sleep duration and sleep quality with incident cardiovascular diseases (CVDs), cancer, and mortality in the same large population. This study aimed at estimating the independent risk factors of long or short sleep durations and several typical characteristics of poor sleep quality for incident CVDs, cancer, and mortality., Methods: In this prospective cohort study, 407 500 individuals were enrolled. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals (HR, 95%CI) of associations of sleep duration and quality with incident CVDs, cancer, and mortality., Results: Compared with the sleep duration of 7 h, sleep duration of ≤5 h and ≥9 h were both associated with higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.16-1.34 and HR = 1.30, 95% CI: 1.22-1.38, respectively), CVD mortality (HR = 1.27, 95% CI: 1.09-1.49 and HR = 1.32, 95% CI: 1.16-1.50, respectively), and CVD incidence (HR = 1.23, 95% CI: 1.16-1.31 and HR = 1.08, 95% CI: 1.02-1.15, respectively). Additionally, long sleep duration (≥9 h) was associated with a higher risk of cancer mortality (HR = 1.19, 95% CI: 1.10-1.30) and cancer incidence (HR = 1.08, 95% CI: 1.04-1.12). Moreover, CVD incidence was significantly associated with snoring, insomnia and narcolepsy, increasing the risk by 7%, 26%, and 20%, respectively., Conclusion: Long sleep durations may substantially increase the risk of mortality and morbidity. Snoring, insomnia, and narcolepsy were independent risk factors for incident CVD., (Copyright © 2021 Elsevier B.V. All rights reserved.)