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Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs., Methods: Updated systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Subgroup analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, dosing regimen, or age. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov between May 1, 2020 (end-date of search of our previous meta-analysis) and April 30, 2024. No language restrictions were imposed. Double-blind RCTs supplementing vitamin D for any duration, with placebo or lower-dose vitamin D control, were eligible if approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. The study was registered with PROSPERO (no. CRD42024527191)., Findings: We identified six new RCTs (19 337 participants). Data were obtained for 16 085 (83·2%) participants in three new RCTs and combined with data from 48 488 participants in 43 RCTs identified in our previous meta-analysis. For the primary comparison of any vitamin D versus placebo, the intervention did not statistically significantly affect overall ARI risk (OR 0·94 [95% CI 0·88-1·00], p=0·057; 40 studies; 61 589 participants; I 2 =26·4%). Pre-specified subgroup analysis did not reveal evidence of effect modification by age, baseline vitamin D status, dosing frequency, or dose size. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0·96 [95% CI 0·90-1·04]; 38 studies; I 2 =0·0%). A funnel plot showed left-sided asymmetry (p=0·0020, Egger's test)., Interpretation: This updated meta-analysis yielded a similar point estimate for the overall effect of vitamin D supplementation on ARI risk to that obtained previously, but the 95% CI for this effect estimate now includes 1·00, indicating no statistically significant protection., Funding: None., Competing Interests: Declaration of interests ARM reports grants from the Fischer Family Trust, Pharma Nord, DSM Nutritional Products, the AIM Foundation, Cytoplan, and Thornton & Ross outside the submitted work. CG reports grants from the Health Technology Assessment Program of the UK National Institute of Health Research during conduct of the study and is supported by the National Institute for Health and Care Research ARC North Thames. The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care. WJ reports grants from Chiesi and AstraZeneca outside the submitted work. REN reports grants from the Australian National Health and Medical Research Council during the conduct of the study. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: This large population-based study aimed to investigate whether arterial stiffness, assessed oscillometrically, was associated with incident diabetes/prediabetes., Methods: The study sample comprised 4240 participants from the Vitamin D Assessment (ViDA) Study (mean±SD age = 66 ± 8). Arterial stiffness was assessed from 5 April 2011-6 November 2012 by way of aortic PWV (aPWV) and estimated carotid-femoral PWV (ecfPWV). Incident diabetes/prediabetes was determined by linkage to dispensed prescription and national hospital discharge registers. Cox proportional hazards regression was used to assess the risk of diabetes/prediabetes in relation to chosen arterial stiffness measures both overall and over quartiles., Results: During a mean±SD follow-up of 10.5 ± 0.4 years, 470 participants developed diabetes/prediabetes. Following adjustment for potential confounders, aPWV (hazard ratio (HR) per SD increase, 1.40, 95 % CI, 1.19-1.64) was associated with the incidence of diabetes. The risk of incident diabetes was, compared to the first quartile, higher in the fourth quartile of aPWV (HR, 1.98, 95 %CI, 1.26-3.11)(P trend =0.01)., Conclusions: Arterial stiffness, as measured by aPWV may be a useful predictor of incident diabetes that can be utilized in clinical practice., Competing Interests: Conflict of Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This systematic review and meta-analysis assesses the association of arterial stiffness with age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO) and retinopathy (diabetic and hypertensive)., Methods: Medline and Embase were systematically searched for observational studies of arterial stiffness and eye disease. Cohort studies were included if they estimated arterial stiffness using any measures based on the arterial waveform, with cross-sectional and case-control studies limited to measures of pulse wave velocity. We assessed the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation., Results: The systematic review of 61 studies (six for AMD, ten for glaucoma, six for RVO and 39 for retinopathy) showed that arterial stiffness overall was higher in people with eye disease than people without eye disease. Forty-four cross-sectional and case-control studies were included in the meta-analysis. Arterial stiffness estimated by way of pulse wave velocity was associated with AMD (mean difference: 0.92 m/s, 95% CI 0.37 to 1.46; 2 studies; n=381; low certainty evidence), glaucoma (mean difference: 0.97 m/s, 95% CI 0.31 to 1.64; 7 studies; n=3418; low certainty evidence), RVO (mean difference: 2.79 m/s, 95% CI 2.02 to 3.55; 5 studies; n=414; very low certainty evidence) and retinopathy (1.48 m/s, 95% CI 0.1.16 to 1.81; 22 studies; n=10 074; low certainty evidence). The 19 cohort studies identified (five for AMD, three for glaucoma, one for RVO and 10 for retinopathy) indicated overall that increased arterial stiffness was associated with the future development of eye disease., Conclusions: Higher arterial stiffness is associated with AMD, glaucoma, RVO and retinopathy PROSPERO REGISTRATION NUMBER: CRD42019129563., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: To investigate whether arterial stiffness, assessed oscillometrically, is associated with incident glaucoma in the Vitamin D Assessment (ViDA) Study cohort, aged 50 to 84 years., Design: Prospective, population-based cohort study., Methods: Arterial stiffness was assessed in 4,713 participants without known glaucoma (mean ± SD age = 66 ± 8 years) from 5 April 2011 to 6 November 2012 by way of aortic PWV (aPWV), estimated carotid-femoral PWV (ePWV) and aortic PP (aPP). Incident glaucoma was identified through linkage to national prescription and hospital discharge registers. Relative risks of glaucoma for each arterial stiffness measure were estimated by Cox proportional hazards regression, over the continuum of values and by quartiles., Results: During a mean ± SD follow-up of 10.5±0.4 years, 301 participants developed glaucoma. Arterial stiffness, as measured by aPWV (Hazard ratio (HR) per SD increase, 1.36, 95% CI 1.14-1.62) and ePWV (HR per SD increase, 1.40, 95% CI 1.14-1.71) but not aPP (HR per SD increase, 1.06, 95% CI 0.92-1.23) was associated with incident glaucoma. When arterial stiffness was analyzed as a categorical variable, the highest quartiles of aPWV (HR, 2.62, 95% CI 1.52-4.52; P trend = .007), ePWV (HR, 2.42, 95%CI 1.37-4.27; P trend = .03), and aPP (HR, 1.68, 95%CI 1.10-2.5; P trend = .02) were associated with the development of glaucoma., Conclusions: Arterial stiffness measured with a simple oscillometric device predicted the development of glaucoma and could potentially be used in clinical practice to help identify people at risk of this condition. It may also present a new therapeutic research avenue, including in respect of systemic antihypertensives., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are numerous cross-sectional studies showing an association between arterial stiffness and diabetes, but the temporality of the association is unclear., Objective: To investigate the temporal relationship between arterial stiffness and diabetes., Methods: We searched MEDLINE and Embase from inception to 31 August 2023, to identify cohort studies that assessed whether arterial stiffness, as measured by pulse wave velocity (PWV), was predictive of the development of diabetes and vice versa. We summarised study data, and where possible undertook meta-analysis., Results: We identified 19 studies that included people with type 1, type 2 and gestational diabetes. All 11 studies investigating arterial stiffness as a predictor of diabetes found a significant relationship. Six of those studies were suitable for meta-analysis. The risk of developing diabetes was greater in people with higher PWV at baseline than lower PWV (RR = 2.14, 95%CI 1.65 to 2.79, p < 0.00001) and the mean difference in baseline PWV was higher in people who developed diabetes than those who did not (mean difference: 0.77 m/s, 95%CI 0.47 to 1.06, p < 0.00001). Of 8 studies investigating diabetes as a predictor of arterial stiffness, 7 found a significant relationship., Conclusion: There is evidence of a bidirectional relationship between arterial stiffness and diabetes. Arterial stiffness may provide a causal link between diabetes and future cardiovascular disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Significant kidney function may be lost before CKD is diagnosed. Arterial stiffness may be a risk factor for CKD and the relationship may be bi-directional. A systematic review of cohort studies was undertaken to ascertain the temporal relationship of arterial stiffness and CKD., Methods: MEDLINE and Embase were searched to 4 October 2023 to identify studies that investigated whether arterial stiffness, as estimated by pulse wave velocity, was predictive of the development or progression of CKD, rapid decline in kidney function, and vice versa. The characteristics and outcomes of the included studies were set out in a qualitative summary. The review protocol is registered with PROSPERO (CRD42019129563)., Results: Forty-two studies were included, all of which were high quality with respect to bias. Thirteen of seventeen studies that investigated arterial stiffness as a predictor of incident CKD found a positive association (p &lt; 0.05). Of the 10 studies that controlled for CKD risk factors, 6 found a positive association. Eight of seventeen studies that investigated arterial stiffness as a predictor of progression of CKD, and five out of eight studies, which investigated rapid kidney decline, found a positive association. One study of six found kidney function was able to predict future elevated arterial stiffness., Conclusion: Arterial stiffness may predict incident CKD and a rapid decline in CKD. It is uncertain if arterial stiffness is associated with CKD progression or whether reduced kidney function is predictive of increased arterial stiffness. Further longitudinal research is required., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Evidence is uncertain about the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and health outcomes in people with type 2 diabetes., Objectives: We aimed to assess the association between vitamin D status and all-cause mortality and cardiovascular disease in people with type 2 diabetes., Methods: We did a systematic search in PubMed, Scopus, CENTRAL, and Web of Science until May 2022. We selected 1) cohort studies investigating the association between serum 25(OH)D concentration and mortality or cardiovascular disease in people with type 2 diabetes or prediabetes and 2) randomized trials of vitamin D supplementation in these patients. We used random-effects pairwise meta-analyses to calculate summary relative risks (RRs) and 95% confidence intervals (CI)., Results: 21 cohort studies and 6 randomized trials were included. Compared with sufficient vitamin D status (≥50 nmol/L), the RR of all-cause mortality was 1.36 (95% CI: 1.23, 1.49; n = 11 studies, GRADE = moderate) for vitamin D insufficiency (25 to <50 nmol/L), and 1.58 (1.33, 1.83; n = 16, GRADE = moderate) for deficiency (<25 nmol/L). Similar findings were observed for cardiovascular mortality and morbidity but not for cancer mortality. The certainty of evidence ranged from very low to moderate. Dose-response meta-analyses indicated nonlinear associations, with the lowest risk at 25(OH)D ∼60 nmol/L for all-cause and cardiovascular mortality. Supplementation with vitamin D did not reduce the risk of all-cause mortality (RR: 0.96, 95% CI: 0.79, 1.16; risk difference per 1000 patients: 3 fewer, 95% CI: 16 fewer, 12 more; n = 6 trials with 7316 participants; GRADE = low) or the risk of cardiovascular mortality and morbidity (very low- to low-certainty evidence)., Conclusions: Vitamin D deficiency and insufficiency are associated with a higher risk of all-cause and cardiovascular mortality in patients with type 2 diabetes or prediabetes. Vitamin D deficiency should be corrected in patients with type 2 diabetes to reach normal serum 25(OH)D concentrations, preferably 60 nmol/L., Systematic Review Registration: This systemic review was registered at PROSPERO as CRD42022326429 (=https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=326429)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Context: Conventional prediction models for vitamin D deficiency have limited accuracy., Background: Using cross-sectional data, we developed models based on machine learning (ML) and compared their performance with those based on a conventional approach., Methods: Participants were 5106 community-resident adults (50-84 years; 58% male). In the randomly sampled training set (65%), we constructed 5 ML models: lasso regression, elastic net regression, random forest, gradient boosted decision tree, and dense neural network. The reference model was a logistic regression model. Outcomes were deseasonalized serum 25-hydroxyvitamin D (25(OH)D) <50 nmol/L (yes/no) and <25 nmol/L (yes/no). In the test set (the remaining 35%), we evaluated predictive performance of each model, including area under the receiver operating characteristic curve (AUC) and net benefit (decision curves)., Results: Overall, 1270 (25%) and 91 (2%) had 25(OH)D <50 and <25 nmol/L, respectively. Compared with the reference model, the ML models predicted 25(OH)D <50 nmol/L with similar accuracy. However, for prediction of 25(OH)D <25 nmol/L, all ML models had higher AUC point estimates than the reference model by up to 0.14. AUC was highest for elastic net regression (0.93; 95% CI 0.90-0.96), compared with 0.81 (95% CI 0.71-0.91) for the reference model. In the decision curve analysis, ML models mostly achieved a greater net benefit across a range of thresholds., Conclusion: Compared with conventional models, ML models predicted 25(OH)D <50 nmol/L with similar accuracy but they predicted 25(OH)D <25 nmol/L with greater accuracy. The latter finding suggests a role for ML models in participant selection for vitamin D supplement trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic syndrome (MetS) is a clustering of metabolic risk factors, including large waist circumference (WC). Other anthropometric parameters and visceral fat mass (VFM) predicted from these may improve MetS detection. Our aim was to assess the ability of such parameters to predict this clustering in a cross-sectional, diagnostic study., Method: Participants were 82 males and 86 females, aged 20-74 years, of Asian Indian ethnicity. VFM was estimated by dual-energy X-ray absorptiometry (DXA) through identification of abdominal subcutaneous fat layer boundaries. Non-anthropometric metabolic risk factors (triglycerides, HDL cholesterol, blood pressure and glucose) were defined using MetS criteria. We estimated the ability of anthropometry and VFM to detect ≥ 2 of these factors by receiver operating characteristic (ROC) and precision-recall curves., Results: Two or more non-anthropometric metabolic risk factors were present in 45 (55%) males and 29 (34%) females. The area under the ROC curve (AUC) to predict ≥ 2 of these factors using WC was 0.67 (95% confidence interval: 0.55-0.79) in males and 0.65 (0.53-0.77) in females. Optimal WC cut-points were 92 cm for males (63% accuracy) and 79 cm for females (53% accuracy). VFM, DXA-measured sagittal diameter and suprailiac skinfold thickness yielded higher AUC point estimates (by up to 0.06), especially in females where these measures improved accuracy to 69%, 69% and 65%, respectively. Pairwise combinations that included WC further improved accuracy., Conclusion: Our findings indicate that cut-points for readily obtained measures other than WC, or in combination with WC, may provide improved detection of MetS risk factor clusters., (© 2022. The Author(s).)