QuestionWhat is the association between oral semaglutide and recognized cardiovascular risk factors vs placebo in the SOUL randomized clinical trial?FindingsIn this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with sustained improvements in multiple cardiovascular risk factors in high-risk participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease receiving standard of care.MeaningThese risk factor benefits may contribute to the overall benefit of oral semaglutide on outcomes for major adverse cardiovascular events, providing supporting evidence for the use of oral semaglutide in cardiovascular risk reduction. ImportanceIndividuals with type 2 diabetes (T2D) are at high risk of atherosclerotic cardiovascular disease (ASCVD). In the SOUL randomized clinical trial, once-daily oral semaglutide reduced risk of major adverse cardiovascular (CV) events by 14% vs placebo in people with T2D and ASCVD and/or chronic kidney disease (CKD) receiving standard of care (SoC); however, whether oral semaglutide modifies recognized CV risk factors in the long term is unclear.ObjectiveTo investigate whether treatment with oral semaglutide was associated with changes in ASCVD risk factors vs placebo.Design, Setting, and ParticipantsThis secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC. Participants underwent randomization from June 2019 to March 2021, with a mean (SD) of 47.5 (10.9) months of follow-up, and data were analyzed from February to December 2025.Intervention(s)Participants were treated with either once-daily oral semaglutide (maximum dose, 14 mg) or placebo, in addition to standard care.Main Outcomes and MeasuresThe primary outcome was the association of oral semaglutide vs placebo with glycated hemoglobin (HbA1c), body weight, and blood pressure (BP) using estimated treatment differences (ETDs) and with high-sensitivity C-reactive protein (hsCRP) and lipid plasma levels using estimated treatment ratios (ETRs).ResultsOf 9650 randomized participants (mean [SD] age, 66.1 (7.6) years; 2790 female participants [28.9%]), 9495 participants (98.4%) completed the trial. Early (13 weeks) improvements in HbA1c (-0.87 percentage points), body weight (-2.54%), systolic BP (SBP, -3.84 mm Hg), pulse pressure (-3.81 mm Hg), hsCRP (-18.08%), total cholesterol (TC, -7.00%), non-high-density lipoprotein cholesterol (non-HDL-C, -8.02%), HDL-C (-4.49%), and triglycerides (-8.15%) were observed with oral semaglutide vs placebo and sustained over the trial duration. Body weight reductions were gradual across both groups. At week 156, in favor of oral semaglutide were ETDs for HbA1c (-0.47 percentage points; 95% CI, -0.52 to -0.42), body weight (-3.26 percentage points; 95% CI, -3.55 to -2.98), SBP (-1.83 mm Hg; 95% CI, -2.47 to -1.18), and pulse pressure (-2.17 mm Hg; 95% CI, -2.72 to -1.61) and ETRs for hsCRP (0.77; 95% CI, 0.74-0.81), TC (0.99; 95% CI, 0.98-1.00), non-HDL-C (0.98; 95% CI, 0.97-0.99), HDL-C (1.01; 95% CI, 1.01-1.02), and triglycerides (0.94; 95% CI, 0.93-0.96). No significant treatment differences were observed for low-density lipoprotein cholesterol or diastolic BP.Conclusions and RelevanceIn this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with early and sustained improvements vs placebo in multiple ASCVD risk factors in high-risk participants with T2D and ASCVD and/or CKD, incremental to SoC.Trial RegistrationClinicalTrials.gov Identifier: NCT03914326 This post hoc secondary analysis of the SOUL randomized clinical trial investigates whether treatment with oral semaglutide was associated with changes in atherosclerotic cardiovascular disease risk factors vs placebo among participants with type 2 diabetes.

Importance:Individuals with type 2 diabetes (T2D) are at high risk of atherosclerotic cardiovascular disease (ASCVD). In the SOUL randomized clinical trial, once-daily oral semaglutide reduced risk of major adverse cardiovascular (CV) events by 14% vs placebo in people with T2D and ASCVD and/or chronic kidney disease (CKD) receiving standard of care (SoC); however, whether oral semaglutide modifies recognized CV risk factors in the long term is unclear. Objective:To investigate whether treatment with oral semaglutide was associated with changes in ASCVD risk factors vs placebo. Design, Setting, and Participants:This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC. Participants underwent randomization from June 2019 to March 2021, with a mean (SD) of 47.5 (10.9) months of follow-up, and data were analyzed from February to December 2025. Intervention(s):Participants were treated with either once-daily oral semaglutide (maximum dose, 14 mg) or placebo, in addition to standard care. Main Outcomes and Measures:The primary outcome was the association of oral semaglutide vs placebo with glycated hemoglobin (HbA1c), body weight, and blood pressure (BP) using estimated treatment differences (ETDs) and with high-sensitivity C-reactive protein (hsCRP) and lipid plasma levels using estimated treatment ratios (ETRs). Results:Of 9650 randomized participants (mean [SD] age, 66.1 (7.6) years; 2790 female participants [28.9%]), 9495 participants (98.4%) completed the trial. Early (13 weeks) improvements in HbA1c (-0.87 percentage points), body weight (-2.54%), systolic BP (SBP, -3.84 mm Hg), pulse pressure (-3.81 mm Hg), hsCRP (-18.08%), total cholesterol (TC, -7.00%), non-high-density lipoprotein cholesterol (non-HDL-C, -8.02%), HDL-C (-4.49%), and triglycerides (-8.15%) were observed with oral semaglutide vs placebo and sustained over the trial duration. Body weight reductions were gradual across both groups. At week 156, in favor of oral semaglutide were ETDs for HbA1c (-0.47 percentage points; 95% CI, -0.52 to -0.42), body weight (-3.26 percentage points; 95% CI, -3.55 to -2.98), SBP (-1.83 mm Hg; 95% CI, -2.47 to -1.18), and pulse pressure (-2.17 mm Hg; 95% CI, -2.72 to -1.61) and ETRs for hsCRP (0.77; 95% CI, 0.74-0.81), TC (0.99; 95% CI, 0.98-1.00), non-HDL-C (0.98; 95% CI, 0.97-0.99), HDL-C (1.01; 95% CI, 1.01-1.02), and triglycerides (0.94; 95% CI, 0.93-0.96). No significant treatment differences were observed for low-density lipoprotein cholesterol or diastolic BP. Conclusions and Relevance:In this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with early and sustained improvements vs placebo in multiple ASCVD risk factors in high-risk participants with T2D and ASCVD and/or CKD, incremental to SoC. Trial Registration:ClinicalTrials.gov Identifier: NCT03914326.

Abstract In this study, we investigated whether a structured aerobic exercise programme could enhance microRNA‐126 (miR‐126) expression and improve subclinical atherosclerosis markers [carotid intima–media thickness (CIMT) and ankle–brachial index (ABI)] in individuals with prediabetes. In this 12 week, multicentre, assessor‐blinded, randomized controlled trial, 64 adults aged 18–60 years with newly diagnosed prediabetes were randomized into exercise and control groups. The exercise group performed supervised moderate‐intensity aerobic exercise programme three times per week (treadmill and cycling, 50%–70% of maximum heart rate), and both groups received standard lifestyle advice. Circulating miR‐126 expression was assessed via ΔCt using qPCR at baseline and week 12. The mean age was 46.82 ± 7.94 years, and 75.0% were female. Within‐ and between‐group comparisons of ΔCt miR‐126 were evaluated using a two‐way repeated‐measures ANOVA, demonstrating a significant main effect of time (P < 0.001) and a significant group × time interaction (P = 0.007). A significant group × time interaction was observed for both ABI and CIMT, with the exercise group showing an increase in ABI and a reduction in CIMT compared with the control group (ABI, P = 0.017; CIMT, P = 0.007). Correlation analysis revealed a positive association between change in ΔCt and CIMT (r = 0.260, P = 0.045) and a negative correlation with ABI (r = −0.275, P = 0.034). A 12 week aerobic exercise intervention significantly increased miR‐126 expression and was associated with improvements in vascular markers of subclinical atherosclerosis, as evidenced by reduced CIMT and increased ABI. These vascular changes might be influenced, in part, by miR‐126‐related endothelial pathways among multiple mechanisms, highlighting the potential of miR‐126 as a biomarker and therapeutic target for early vascular protection in prediabetes.

To determine the prevalence, severity, and morphological subtypes of anemia among adults aged 35–70 years in Türkiye and to examine their distribution according to sex, age, educational level, and urban–rural residence. Cross-sectional analysis of baseline data from a nationally representative prospective cohort study. Community-based study conducted in urban and rural areas across eight provinces in Türkiye. A total of 4,050 adults aged 35–70 years enrolled in the Prospective Urban Rural Epidemiology (PURE) Türkiye cohort between 2008 and 2009 with available hemoglobin measurements. Anemia was defined and classified according to World Health Organization criteria. Primary outcomes were the prevalence and severity of anemia. Secondary outcomes included morphological subtypes based on mean corpuscular volume, mean corpuscular hemoglobin concentration, and red cell distribution width, as well as associations with sociodemographic characteristics and estimated dietary iron and vitamin B12 intake. Overall, 13.6% of participants had anemia, with a significantly higher prevalence in women than in men (19.3% vs. 4.8%; p < 0.001). Microcytic anemia was the most common subtype (51.9%), followed by normocytic anemia (48.1%). Among individuals with anemia, approximately 37% had hypochromic microcytic anemia with elevated red cell distribution width, suggestive of iron deficiency. Anemia prevalence showed an inverse association with educational level (p = 0.009) and was slightly higher in urban than in rural areas (14.4% vs. 12.2%; p = 0.049). Estimated dietary iron and vitamin B12 intake did not differ significantly across anemia subtypes or hemoglobin categories, except for lower vitamin B12 intake among anemic men. Anemia affects a substantial proportion of adults aged 35–70 years in Türkiye, particularly women and individuals with lower educational attainment. The predominance of hypochromic microcytic anemia indicates that iron deficiency and non-nutritional factors may play an important role. These findings support the need for targeted public health strategies and routine anemia screening in high-risk adult populations.

BACKGROUND Inadequate glycemic control in patients with type 2 diabetes (T2DM) is a major public health problem and a significant risk factor for the progression of diabetic complications. AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin (HbA1c) ≥ 10% and varying backgrounds of glycemic control. METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months. Participants were categorized into four groups based on prior glycemic history: Newly diagnosed, previously well controlled with recent worsening, previously off-target but now worsening, and HbA1c consistently above 10%. HbA1c levels were monitored quarterly, and patients received medical, educational, and dietary support as needed. The analysis focused on the success rates of good glycemic control and the associated factors within each group. RESULTS The study showed significant improvements in HbA1c levels in all participants. The most significant improvement was observed in individuals newly diagnosed with diabetes: 65% achieved an HbA1c target of ≤ 7%. The results varied between participants with different glycemic control histories, followed by decreasing success rates: 39% in participants with previously good glycemic control, 21% in participants whose glycemic control had deteriorated compared to before, and only 10% in participants with persistently poor control, with mean HbA1c levels of 6.3%, 7.7%, 8.2%, and 9.7%, respectively. After one year, 65.2% of the “newly diagnosed patients”, 39.3% in the “previously controlled group”, 21.9% in the “previously off-target but now worsened'” group and 10% in the “poorly controlled from the start” group had achieved HbA1c levels of 7 and below. CONCLUSION In poorly controlled diabetes, the rate at which treatment goals are achieved is associated with the glycemic background characteristics, emphasizing the need for tailored strategies. Therefore, different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.

ABSTRACTAimsGrowth differentiation factor‐15 (GDF‐15) is an inflammatory cytokine that increases in prediabetes and is known for its anorexigenic effects. This study aims to evaluate the effects of a 12‐week exercise program on GDF‐15 in individuals with prediabetes.Materials and MethodsIn this multicenter, parallel‐group, randomized‐controlled trial, 64 patients aged 18–60 diagnosed with prediabetes were randomized in a 1:1 ratio into the exercise group (E) and the control group (C). Additionally, 32 patients who were planned to start metformin were included in the metformin group (M). Participants in the exercise group engaged in aerobic exercise at 50–70% of their maximum heart rate for 60 min, 3 days a week. Serum GDF‐15 levels were evaluated at the beginning and the end of the 12th week.ResultsThe mean age of the 91 participants who completed the study was 46.13 ± 8.52 years, and 23.1% were male. Basal GDF‐15 levels were similar among the groups (E = 668.6 ± 415.1, C = 651.8 ± 352.5, M = 603.6 ± 387.2, P = 0.47). At the 12th week, GDF‐15 levels were lower in the E compared to the C, while higher in the M compared to the C (E = 383.1 ± 215.6, C = 556.4 ± 285.6, M = 810.8 ± 498.0, P < 0.001). In inter‐group comparisons, no significant change was observed in the C between the 0th and 12th weeks, while GDF‐15 decreased in the E (P < 0.001) and increased in the M (P < 0.001).ConclusionsIt was determined that in individuals with prediabetes, GDF‐15, which serves both as a biomarker of metabolic disorder and has a negative regulatory effect on appetite, decreased with 12 weeks of aerobic exercise and increased with metformin administration.

Background and objectives Acute stroke is associated with a spectrum of functional deficits. The objective of this analysis was to explore whether the importance of individual risk factors differ by stroke severity, which may be of relevance to public health strategies to reduce disability. Methods INTERSTROKE is an international case-control study of risk factors of first acute stroke (recruitment 2007-August 2015) in 32 countries. Stroke severity was measured using the modified Rankin Scale (mRS) score within 72 hours of admission to hospital. Severe stroke is defined as mRS scores of 4-6 (and non-severe stroke, score of 0-3). We used multinomial logistic regression to estimate comparative odds ratios (ORs; 95% CIs) for severe and non-severe stroke and tested for heterogeneity (p(heterogeneity)). We also conducted a matched case-case analysis (matched for age, sex, country, and primary stroke subtype) to determine whether the prevalence of risk factors differed significantly between severe and non-severe stroke. A significant difference in the association of a risk factor of severe stroke compared with non-severe stroke was defined as p < 0.05 for both p(heterogeneity) and p(case-case). Results Of patients with acute stroke (n = 13,460), 64.0% (n = 8,612) were reported to have mRS scores of 0-3 and 36.0% (n = 4,848) scores of 4-6. The mean age was 61.7 years for patients with non-severe stroke and 62.9 years for patients with severe stroke (p = 0.72). 38.1% (n = 3,278) of patients with non-severe stroke and 44.6% (n = 2,162) of patients with severe stroke were female. Hypertension (OR 3.21; 95% CI 2.97-3.47 for severe stroke, OR 2.87; 95% CI 2.69-3.05 for non-severe stroke; p(heterogeneity) = 0.03; p(case-case) < 0.001), atrial fibrillation (OR 4.70; 95% CI 4.05-5.45 for severe stroke, OR 3.61; 95% CI 3.16-4.13 for non-severe stroke; p(heterogeneity) = 0.009; p(case-case) < 0.001), and smoking (OR 1.87; 95% CI 1.72-2.03 for severe stroke, OR 1.65; 95% CI 1.54-1.77 for non-severe stroke; p(heterogeneity) = 0.02; p(case-case) < 0.001) had a stronger association with severe stroke, compared with non-severe stroke. The waist-to-hip ratio had a stronger association with non-severe stroke compared with severe stroke (p(heterogeneity) < 0.001; p(case-case) < 0.001). Discussion Hypertension, atrial fibrillation, and smoking had a stronger magnitude of association with severe stroke (compared with non-severe stroke) while the increased waist-to-hip ratio had a stronger magnitude of association with non-severe stroke.

Objective: The aim of the study was to evaluate the effectiveness and safety of insulin glargine 300 U/ mL (Gla-300) in insulin-naive patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drug (OADs) treatment in Turkey. Methods: One hundred eight patients from 20 centers enrolled in the study. Starting from baseline, Gla-300 was self-administered subcutaneously and once daily in the evening. The primary outcome was the mean change in glycated hemoglobin A1c (HbA1c) from baseline to week 24. Results: The mean (+/- SD) Hb1Ac level of 9.4% (+/- 0.8) at baseline decreased to 7.5% (+/- 0.9) at week 12 (P < .1) and to 7.3% (+/- 0.9) at week 24 (P < .1). Although none of the patients were within the target Hb1Ac level of <= 7% at baseline, the percentage of patients who achieved the target Hb1Ac level was 30.4% at week 12 and increased to 42.9% at week 24. Gla-300 treatment achieved the Hb1Ac target in 21 (19.4%) patients without experiencing a hypoglycemic event and in 27 (25.0%) patients who experienced at least one hypoglycemic event. For each self-monitoring blood glucose time point, significant improvements were observed as compared to baseline (P < .001). Statistically significant improvement (P < .001) was seen in the treatment satisfaction questionnaire - status version scores between baseline and week 24. Conclusion: This study indicated that Gla-300 is effective to provide a successful glycemic control with low risk of hypoglycemia added to OADs in insulin-naive patients with T2DM, and it has the potential to improve the quality of life of patients.

Background The focus of most epidemiological studies has been mortality or clinical events, with less information on activity limitations related to basic daily functions and their consequences. Standardised data from multiple countries at different economic levels in different regions of the world on activity limitations and their associations with clinical outcomes are sparse. We aimed to quantify the prevalence of activity limitations and use of assistive devices and the association of limitations with adverse outcomes in 25 countries grouped by different economic levels. Methods In this analysis, we obtained data from individuals in 25 high-income, middle-income, and low-income countries from the Prospective Urban Rural Epidemiological (PURE) study (175 660 participants). In the PURE study, individuals aged 35-70 years who intended to continue living in their current home for a further 4 years were invited to complete a questionnaire on activity limitations. Participant follow-up was planned once every 3 years either by telephone or in person. The activity limitation screen consisted of questions on self-reported difficulty with walking, grasping, bending, seeing close, seeing far, speaking, hearing, and use of assistive devices (gait, vision, and hearing aids). We estimated crude prevalence of self-reported activity limitations and use of assistive devices, and prevalence standardised by age and sex. We used logistic regression to additionally adjust prevalence for education and socioeconomic factors and to estimate the probability of activity limitations and assistive devices by age, sex, and country income. We used Cox frailty models to evaluate the association between each activity limitation with mortality and clinical events (cardiovascular disease, heart failure, pneumonia, falls, and cancer). The PURE study is registered with ClinicalTrials.gov, NCT03225586. Findings Between Jan 12, 2001, and May 6, 2019, 175 584 individuals completed at least one question on the activity limitation questionnaire (mean age 506 years [SD 98]; 103 625 [59%] women). Of the individuals who completed all questions, mean follow-up was 107 years (SD 44). The most common self-reported activity limitations were difficulty with bending (23 921 [136%] of 175 515 participants), seeing close (22 532 [134%] of 167 801 participants), and walking (22 805 [130%] of 175 554 participants); prevalence of limitations was higher with older age and among women. The prevalence of all limitations standardised by age and sex, with the exception of hearing, was highest in low-income countries and middle-income countries, and this remained consistent after adjustment for socioeconomic factors. The use of gait, visual, and hearing aids was lowest in low-income countries and middle-income countries, particularly among women. The prevalence of seeing close limitation was four times higher (6257 [165%] of 37 926 participants vs 717 [40%] of 18 039 participants) and the prevalence of seeing far limitation was five times higher (4003 [106%] of 37 923 participants vs 391 [22%] 2 2%] of 18 038 participants) in low-income countries than in high- income countries, but the prevalence of glasses use in low-income countries was half that in high-income countries. Walking limitation was most strongly associated with mortality (adjusted hazard ratio 132 [95% CI 125-139]) and most consistently associated with other clinical events, with other notable associations observed between seeing far limitation and mortality, grasping limitation and cardiovascular disease, bending limitation and falls, and between speaking limitation and stroke. Interpretation The global prevalence of activity limitations is substantially higher in women than men and in lowincome countries and middle-income countries compared with high-income countries, coupled with a much lower use of gait, visual, and hearing aids. Strategies are needed to prevent and mitigate activity limitations globally, with particular emphasis on low-income countries and women.

AimsWaist circumference (WC) is a reliable obesity surrogate but may not distinguish between visceral and subcutaneous adipose tissue. Our aim was to develop a novel sex-specific model to estimate the magnitude of visceral adipose tissue measured by computed tomography (CT-VAT).MethodsThe model was initially formulated through the integration of anthropometric measurements, laboratory data, and CT-VAT within a study group (n=185), utilizing the Multivariate Adaptive Regression Splines (MARS) methodology. Subsequently, its correlation with CT-VAT was examined in an external validation group (n=50). The accuracy of the new model in estimating increased CT-VAT (>130 cm2) was compared with WC, body mass index (BMI), waist-hip ratio (WHR), visceral adiposity index (VAI), a body shape index (ABSI), lipid accumulation product (LAP), body roundness index (BRI), and metabolic score for visceral fat (METS-VF) in the study group. Additionally, the new model’s accuracy in identifying metabolic syndrome was evaluated in our Metabolic Healthiness Discovery Cohort (n=430).ResultsThe new model comprised WC, gender, BMI, and hip circumference, providing the highest predictive accuracy in estimating increased CT-VAT in men (AUC of 0.96 ± 0.02), outperforming other indices. In women, the AUC was 0.94 ± 0.03, which was significantly higher than that of VAI, WHR, and ABSI but similar to WC, BMI, LAP, BRI, and METS-VF. It’s demonstrated high ability for identifying metabolic syndrome with an AUC of 0.76 ± 0.03 (p<0.001).ConclusionThe new model is a valuable indicator of CT-VAT, especially in men, and it exhibits a strong predictive capability for identifying metabolic syndrome.

Objective: This study aimed to investigate the associations between albuminuria and visceral adiposity in patients with type 2 diabetes (T2D). Materials and methods: This single-center crosssectional study included patients with T2D. Anthropometric measurements, urine analyses, and fasting blood tests, were conducted. Patients diagnosed with hepatosteatosis within the past 3 months were invited to undergo transthoracic echocardiography to measure epicardial fat thickness (EFT). The clinical, laboratory, and imaging findings of patients with microalbumi- nuria (> 30 mg/day) were compared with those of patients without microalbuminuria using chi-square tests and t-tests. Results: The study included 702 patients with a mean age of 58.9 +/- 10.9 years and a male predominance (57.8%). Microalbuminuria was present in 253 patients (36%). In the group with microalbuminuria, age, levels of glucose, triglycerides, HbA1c, FIB-4, and visceral adi posity index (VAI) scores were higher, while glomerular filtration rate (GFR), high-density lipoprotein (HDL) cholesterol levels, and the frequency of hypertension were lower compared to the patients without microalbuminuria (p < 0.05 for all). Out of 169 patients who underwent liver ultrasonography, hepatosteatosis was observed in 138 individuals (81.7%). Among the 59 patients who underwent echocardiography, an increased EFT was found in 25 (42.4%) patients. No significant differences were observed in EFT, hepatic steatosis presence, or stage between the microalbuminuria and non-microalbuminuria groups (p = 0.807, 0.834, and 0.351, respectively). Conclusions: While no associations were found between microalbuminuria and hepatosteatosis or EFT, patients with microalbuminuria showed higher VAI and FIB-4 scores. The findings underscore the potential of these scores in predicting microalbuminuria in patients with T2D.

Background: This study aimed to assess the influence of hypokalemia on mortality among hospitalized patients diagnosed with COVID-19 pneumonia. Methods: A cohort of 300 patients aged>18 diagnosed with COVID-19 pneumonia were included in this study. Demographic data, symptoms, comorbidities, medications, duration of hospitalization, and blood potassium levels were recorded, and hypokalemia was defined as having at least three potassium values below 3.5 mmol/L within the first five days of hospitalization. The study investigated whether hypokalemia serves as a risk factor for mortality in COVID-19 patients. Results: Among the 300 patients, 57 (19%) were identified with hypokalemia. Patients with hypokalemia were older compared to those without this disturbance (P=0.012). No significant correlation was found between hypokalemia and the presence of diabetes mellitus (P=0.999), hypertension (P=0.193), or cardiovascular disease (P=0.781). However, patients with hypokalemia had a higher usage rate of diuretics (P=0.035). The use of corticosteroids, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, insulin, beta-2 agonists, beta-blockers, antipsychotic drugs, and digoxin was similar between patients with and without hypokalemia (P>0.05). Hypokalemia was associated with a 4.79-fold increase in mortality (P=0.003), and each additional day of hospitalization increased mortality by 1.14 times (P<0.001). Conclusion: Advanced age and diuretic usage could elevate the risk of hypokalemia in COVID-19 patients. Prolonged hospital stays and higher mortality rates among patients with hypokalemia suggest a need for the careful management of electrolyte imbalances.

BACKGROUND:The built environment can influence human health, but the available evidence is modest and almost entirely from urban communities in high-income countries. Here we aimed to analyse built environment characteristics and their associations with obesity in urban and rural communities in 21 countries at different development levels participating in the Prospective Urban and Rural Epidemiology (PURE) Study. METHODS:Photographs were acquired with a standardised approach. We used the previously validated Environmental Profile of a Community's Health photo instrument to evaluate photos for safety, walkability, neighbourhood beautification, and community disorder. An integrated built environment score (ie, a minimum of 0 and a maximum of 20) was used to summarise this evaluation across built environment domains. Associations between built environment characteristics, separately and combined in the integrated built environment score, and obesity (ie, a BMI >30kg/m2) were assessed using multilevel regression models, adjusting for individual, household, and community confounding factors. Attenuation in the associations due to walking was examined. FINDINGS:Analyses include 143 338 participants from 530 communities. The mean integrated built environment score was higher in high-income countries (13·3, SD 2·8) compared with other regions (10·1, 2·5) and urban communities (11·2, 3·0). More than 60% of high-income country communities had pedestrian safety features (eg, crosswalks, sidewalks, and traffic signals). Urban communities outside high-income countries had higher rates of sidewalks (176 [84%] of 209) than rural communities (59 [28%] of 209). 15 (5%) of 290 urban communities had bike lanes. Litter and graffiti were present in 372 (70%) of 530 communities, and poorly maintained buildings were present in 103 (19%) of 530. The integrated built environment score was significantly associated with reduced obesity overall (relative risk [RR] 0·58, 95% CI 0·35-0·93; p=0·025) for high compared with low scores and for increasing trend (0·85, 0·78-0·91; p<0·0001). The trends were statistically significant in urban (0·85, 0·77-0·93; p=0·0007) and rural (0·87, 0·78-0·97; p=0·015) communities. Some built environment features were associated with a lower prevalence of obesity: community beautification RR 0·75 (95% CI 0·61-0·92; p=0·0066); bike lanes RR 0·58 (0·45-0·73; p<0·0001); pedestrian safety RR 0·75 (0·62-0·90; p=0·0018); and traffic signals RR 0·68 (0·52-0·89; p=0·0055). Community disorder was associated with a higher prevalence of obesity (RR 1·48, 95% CI 1·17-1·86; p=0·0010). INTERPRETATION:Community built environment features recorded in photographs, including bike lanes, pedestrian safety measures, beautification, traffic density, and disorder, were related to obesity after adjusting for confounders, and stronger associations were found in urban than rural communities. The method presents a novel way of assessing the built environment's potential effect on health. FUNDING:Population Health Research Institute, Hamilton Health Sciences Research Institute, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research's Strategy for Patient Oriented Research, Ontario Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, and GlaxoSmithKline.

Background:Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods:The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings:Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation:There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding:The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Purpose:It is estimated that type 2 diabetes mellitus affects 530 million people worldwide and 10.5 per cent of these patients have diabetic retinopathy. This study aims to investigate the predictive value of cardiometabolic control, GGT and malnutrition-related inflammation markers for predicting Diabetic retinopathy prevalence and prognosis. Materials and Methods:Type 2 Diabetes Mellitus patients who were consecutively admitted to Internal and Ophthalmology outpatient clinics were included in this study. Clinical, haematological and biochemical data were recorded. Cut-off values of GGT, PNI, NRI and HALP scores were determined by receiver operator characteristic curve analysis. Univariate and multivariate analyses were performed to determine the association of all variables with Diabetic retinopathy. As a result, we evaluated which of these tests were predictive and prognostic for the development of diabetic retinopathy. Results:This study included 166 patients. Fasting blood glucose(p

Metabolically healthy obesity (MHO) refers to obese individuals with a favorable metabolic profile, without severe metabolic abnormalities. This study aimed to investigate the potential of follistatin, a regulator of metabolic balance, as a biomarker to distinguish between metabolically healthy and unhealthy obesity. This cross-sectional study included 30 metabolically healthy and 32 metabolically unhealthy individuals with obesity. Blood samples were collected to measure the follistatin levels using an enzyme-linked immunosorbent assay (ELISA). While follistatin did not significantly differentiate between metabolically healthy (median 41.84 [IQR, 37.68 to 80.09]) and unhealthy (median 42.44 [IQR, 39.54 to 82.55]) individuals with obesity (p = 0.642), other biochemical markers, such as HDL cholesterol, triglycerides, C-peptide, and AST, showed significant differences between the two groups. Insulin was the most significant predictor of follistatin levels, with a coefficient of 0.903, followed by C-peptide, which exerted a negative influence at −0.624. Quantile regression analysis revealed nuanced associations between the follistatin levels and metabolic parameters in different quantiles. Although follistatin may not serve as a biomarker for identifying MHO and metabolically unhealthy obesity, understanding the underlying mechanisms that contribute to metabolic dysfunction could provide personalized strategies for managing obesity and preventing associated complications.

BACKGROUND AND PURPOSE:Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS:INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS:Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION:Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

OBJECTIVE:The rate of cardiovascular disease is increasing in developed countries progressively with estimates predicting 22 million by 2030. Based on these cardiovascular events lies atherosclerosis, a condition intricately linked to chronic inflammatory processes. Among fundamental clinical biomarkers, C-reactive protein (CRP) stands out as a backbone of inflammatory activity. Notably, the excessive production of CRP, often linked with obesity, plays a pivotal role in the dysregulation of triglyceride apo B-100 fractional catabolism, thus emerging as a significant cardiovascular risk factor. Apart from atherosclerotic processes, the interplay between high CRP levels and impaired fasting glucose (IFG) is also gaining recognition as a messenger of disrupted glucose metabolism, potentially ushering in the onset of a prediabetic state. METHODS:Our retrospective analysis scrutinized the biochemical data - namely low-density lipoprotein cholesterol (LDL-C), triglycerides, fasting blood sugar, and CRP levels-of 3500 patients from an internal medicine outpatient clinic seen from August 2006 to May 2007. Our objective was to dissect the correlations among these parameters. Exclusion criteria were omitting individuals with acute or chronic inflammation, known inflammatory diseases, diagnosed diabetes, coronary artery disease, lipid metabolism disorders, those on lipid-lowering agents, and anyone outside the age bracket of 18-65 years. This study was conducted in strict adherence to the ethical principles outlined in the Declaration of Helsinki. RESULTS:As a result of our study, the ratio of CRP levels above 0.8 was significantly higher in patients with IFG according to the World Health Organization criteria (6.1-6.9 mmol/L or 109-124 mg/dL) than in individuals with normal fasting glucose (70-108 mg/dL). (19.7%, 17.2%, respectively) (p<0.001). In addition, the ratio of CRP levels above 0.8 was also higher in patients with triglyceride levels between 151 and 199 mg/dL) and over 500 mg/dL. (23.2%, 24.1%, respectively) (p<0.012). However, the relationship between CRP levels and LDL-C total cholesterol was not statistically significant (p>0.05). CONCLUSION:This retrospective study suggests the imperative for a proactive approach in the clinical evaluation of patients exhibiting elevated CRP, especially in the context of preemptive management of prediabetes. In light of these findings, we think that elevated CRP may be a warning sign for prediabetic status and may be useful in early diagnosis.