Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population.

OBJECTIVES: To evaluate some confounding factors that influence the concentrations of S100 calcium binding protein B (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxyl-terminal hydrolase L-1 (UCH-L1) in older individuals. Indeed, recent guidelines have proposed the combined use of S100B and the "GFAP-UCH-L1" mTBI test to rule out mild traumatic brain injuries (mTBI). As older adults are the most at risk of mTBI, it is particularly important to understand the confounding factors of those mTBI rule-out biomarkers in aging population. METHODS: The protein S100B and the "GFAP and UCH-L1" mTBI test were measured using Liaison XL (Diasorin) and Alinity I (Abbott), respectively, in 330 and 341 individuals with non-suspected mTBI from the SarcoPhAge cohort. RESULTS: S100B, GFAP and UCH-L1 were all significantly correlated with renal function whereas alcohol consumption, Geriatric Depression Score (GDS), smoking habits and anticoagulant intake were not associated with any of these three biomarkers. Body mass index (BMI) and age were associated with GFAP and UCH-L1 expression while sex and mini-mental state examination (MMSE) were only associated with GFAP. According to the manufacturer's cut-offs for mTBI rule-out, only 5.5 % of participants were positive for S100B whereas 66.9 % were positive for the "GFAP-UCH-L1" mTBI test. All positive "GFAP-UCH-L1" mTBI tests were GFAP+/UCH-L1-. Among individuals with cystatin C>1.55 mg/L, 25 % were positive for S100B while 90 % were positive for the mTBI test. CONCLUSIONS: Our data show that confounding factors have different impacts on the positivity rate of the "GFAP-UCH-L1" mTBI test compared to S100B.

The prevalence of sedentary behavior among university students in Saudi Arabia.

BACKGROUND: A considerable body of research has demonstrated that reducing sitting time benefits health. Therefore, the current study aimed to explore the prevalence of sedentary behavior (SB) and its patterns. METHODS: A total of 6975 university students (49.1% female) were chosen randomly to participate in a face-to-face interview. The original English version of the sedentary behavior questionnaire (SBQ) was previously translated into Arabic. Then, the validated Arabic version of the SBQ was used to assess SB. The Arabic SBQ included 9 types of SB (watching television, playing computer/video games, sitting while listening to music, sitting and talking on the phone, doing paperwork or office work, sitting and reading, playing a musical instrument, doing arts and crafts, and sitting and driving/riding in a car, bus or train) on weekdays and weekends. RESULTS: SBQ indicated that the total time of SB was considerably high (478.75 ± 256.60 and 535.86 ± 316.53 (min/day) during weekdays and weekends, respectively). On average, participants spent the most time during the day doing office/paperwork (item number 4) during weekdays (112.47 ± 111.11 min/day) and weekends (122.05 ± 113.49 min/day), followed by sitting time in transportation (item number 9) during weekdays (78.95 ± 83.25 min/day) and weekends (92.84 ± 100.19 min/day). The average total sitting time of the SBQ was 495.09 ± 247.38 (min/day) and 58.4% of the participants reported a high amount of sitting time (≥ 7 hours/day). Independent t-test showed significant differences (P ≤ 0.05) between males and females in all types of SB except with doing office/paperwork (item number 4). The results also showed that male students have a longer daily sitting time (521.73 ± 236.53 min/day) than females (467.38 ± 255.28 min/day). Finally, 64.1% of the males reported a high amount of sitting time (≥ 7 hours/day) compared to females (52.3%). CONCLUSION: In conclusion, the total mean length of SB in minutes per day for male and female university students was considerably high. About 58% of the population appeared to spend ≥7 h/day sedentary. Male university students are likelier to sit longer than female students. Our findings also indicated that SB and physical activity interventions are needed to raise awareness of the importance of adopting an active lifestyle and reducing sitting time.

The single point insulin sensitivity estimator (SPISE) is associated with bone health in Arab adults.

BACKGROUND: The Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ, its associations with non-invasive measures of extra-skeletal functions such as insulin sensitivity warrant investigation. AIMS: This study aimed to explore the relationship between the SPISE index and Bone Mineral Density (BMD) in an adult population. METHODS: Data from a total of 1270 Arab adults (84% females, mean age 56.7 ± 8.1 years) from the Osteoporosis Registry Database of the Chair for Biomarkers of Chronic Diseases in King Saud University, Riyadh, Saudi Arabia was used in this study. T-scores and SPISE were calculated. Regression models were used to determine associations between SPISE and bone health indices. RESULTS: The low BMD group (N = 853; T-score <-1.0) had significantly higher SPISE values than those with normal BMD (N = 417; T-score - 1.0 and above) (4.6 ± 1.3 vs. 4.3 ± 1.2, p < 0.001). Multivariate linear regression, adjusted for covariates, confirmed a significant inverse association between SPISE and BMD for all participants (ß=-0.22, p < 0.001), as well as both groups [normal BMD (ß = -0.10, p = 0.02) and low BMD groups (ß = -0.15, p < 0.001)]. SPISE, family history of T2DM, and history of fractures collectively account for 17% of the variances perceived in T-score for all participants (p < 0.001). CONCLUSIONS: A significant inverse association between the SPISE index and BMD was observed in adults, suggesting a link between BMD and extra-skeletal health. Underlying mechanisms need to be investigated prospectively using BMD as secondary outcomes in lifestyle modification programs.

Circulating Interleukins-33 and -37 and Their Associations with Metabolic Syndrome in Arab Adults.

Interleukins (ILs) are a group of cytokines known to have immunomodulatory effects; they include ILs-33 and -37 whose emerging roles in the pathogenesis of metabolic syndrome (MetS) remain under investigated. In this study, we compared circulating IL-33 and IL-37 in Arab adults with and without MetS to determine its associations with MetS components. A total of 417 Saudi participants (151 males, 266 females; mean age ± SD 41.3 ± 9.0 years; mean body mass index ± SD 30.7 ± 6.3 kg/m2) were enrolled and screened for MetS using the ATP III criteria. Anthropometrics and fasting blood samples were taken for the assessment of fasting glucose and lipids. Circulating levels of IL-33 and IL-37 were measured using commercially available assays. The results showed higher levels of serum IL-33 and IL-37 in participants with MetS than those without (IL-33, 3.34 3.42 (2.3-3.9) vs. (1-3.9), p = 0.057; IL-37, 5.1 (2.2-8.3) vs. 2.9 (2.1-6.1), p = 0.01). Additionally, having elevated levels of IL-33 was a risk factor for hypertension, low HDL-c, and hypertriglyceridemia. A stratification of the participants according to sex showed that males had higher IL-33 levels than females [3.7 (3.0-4.1) vs. 3.15 (1.4-3.8), p < 0.001], while females had higher levels of IL-37 than males [3.01 (2.2-7.0) vs. 2.9 (2.1-5.6), p = 0.06]. In conclusion, the presence of MetS substantially alters the expression of ILs-33 and -37. IL-33 in particular can be potentially used as a therapeutic target to prevent MetS progression. Longitudinal and interventional studies are warranted to confirm present findings.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Validity and reliability of the Arabic sedentary behavior questionnaire among university students aged between 18-30 years old.

PURPOSE: The study aimed to test the validity and reliability of the Arabic version of the sedentary behavior questionnaire (SBQ). METHODS: A total of 624 university students (273 males; 351 females, mean age = 20.8 years) were recruited from Taibah University, Madinah, Saudi Arabia. For criterion and constructive validity (n = 352), the Arabic SBQ was compared with total sitting time from the International Physical Activity Questionnaire-short form (IPAQ-SF) and the International Physical Activity Questionnaire-long form (IPAQ-LF). For concurrent validity, the English and Arabic SBQ versions were given concurrently to bilingual university students (n = 122) once. For test-retest reliability, the Arabic SBQ was given twice to participants (n = 150) at a one-week interval. RESULTS: Sitting time of IPAQ-SF (7th question: sitting time on weekdays) and IPAQ-LF (21st question: sitting time on weekdays and 22nd question: sitting time on weekends) correlated significantly with total sitting time/week of the Arabic SBQ (r = 0.29, p = 0.003; r = 0.14, p = 0.02, respectively). Motorized transportation measured with the IPAQ-LF correlated significantly with time spent driving in a car, bus, or train from the Arabic SBQ on weekdays and weekends (r = 0.53, p < 0.001; r = 0.44 p < 0.001, respectively). The total sitting time of the Arabic SBQ was inversely correlated with BMI (r = -0.18, p = 0.001). The correlations between the Arabic and the English SBQ versions ranged from 0.25-0.96; p < 0.001 on weekdays and 0.50-0.90; p < 0.001 on weekends. Moderate to good reliability was also found between test and retest for all SBQ items and total score during weekdays (0.72 to 0.8), and weekends (0.64 to 0.87), with exception of the 7th item "play musical instrument", ICC = 0.46). Mean difference of test-retest of the Arabic SBQ was not significantly different from zero for the total sitting time of the Arabic SBQ (t = -0.715, P = 0.476). CONCLUSION: The Arabic SBQ had satisfactory levels of reliability, with total sitting time of the Arabic SBQ correlating significantly with sitting times derived from IPAQ-SF, IPAQ-LF, and the English SBQ versions. Hence, the Arabic SBQ can be used as a tool to measure sedentary behavior among adult Arabs aged between 18 to 30 years old in future epidemiologic and clinical practice.

Vitamin D Status Modestly Regulates NOD-Like Receptor Family with a Pyrin Domain 3 Inflammasome and Interleukin Profiles among Arab Adults.

Vitamin D (VD) deficiency has been associated with inflammation and dysregulation of the immune system. The NLRP3 inflammasome, a critical immune response component, plays a pivotal role in developing inflammatory diseases. VD hinders NLRP3 inflammasome activation and thus exerts anti-inflammatory effects. This study aimed to analyze the effect of VD deficiency on circulating levels of NLRP3 inflammasomes (NLRP3 and caspase-1) and associated interleukins (IL-1α, IL-1ß, IL-18, IL-33 and IL-37) in Saudi adults. Methods: A total of 338 Saudi adults (128 males and 210 females) (mean age = 41.2 ± 9.1 years and mean BMI 31.2 ± 6.5 kg/m2) were included. Overnight-fasting serum samples were collected. Participants were stratified according to their VD status. Serum levels of NLRP3 inflammasomes and interleukins of interest were assessed using commercially available immuno-assays. Individuals with VD deficiency had significantly lower mean 25(OH)D levels than those with a normal VD status (29.3 nmol/L vs. 74.2 nmol/L, p < 0.001). The NLRP3 levels were higher in the VD-deficient group than their VD-sufficient counterparts (0.18 vs. 0.16, p = 0.01). Significant inverse associations were observed between NLRP3 levels with age (r = -0.20, p = 0.003) and BMI (r = -0.17, p = 0.01). Stepwise regression analysis identified insulin (ß = 0.38, p = 0.005) and NLRP3 (ß = -1.33, p = 0.03) as significant predictors of VD status, explaining 18.3% of the variance. The findings suggest that the VD status modestly regulates NLRP3 inflammasome and interleukin activities. This may provide novel insights into the pathogenesis and management of inflammatory disorders.

Impact of Vitamin D Status Correction on Serum Lipid Profile, Carboxypeptidase N and Nitric Oxide Levels in Saudi Adults.

This study aimed to determine the impact on the lipid profile, carboxypeptidase N (CPN) and nitric oxide (NOx) associated with vitamin D (VD) status correction among Saudi adults with VD deficiency. A total 111 VD deficient (25(OH)D < 50 nmol/L)) adult Saudis aged 18-50 years old (57 females and 54 males) were enrolled in this 6-month interventional study. They were given 50,000 IU VD weekly for the first 2 months and then twice a month for the next 2 months, followed by 1000 IU daily for the last 2 months. The fasting lipid profile and the blood glucose, VD, NOx and CPN concentrations were measured at baseline and after intervention. Post-supplementation, the median VD was significantly higher (p < 0.001) in females [58.3 (50.6-71.2)] and males [57.8 (51.0-71.8)]. HDL cholesterol significantly increased (p = 0.05) and NOx significantly decreased (p = 0.02) in males post-supplementation. Triglycerides were positively associated with NOx in all subjects before (r = 0.44, p = 0.01) and after (r = 0.37, p = 0.01) VD status correction. There was a significant increase in serum levels of CPN2 (p = 0.02) in all subjects. Furthermore, CPN was inversely correlated with NOx (r = -0.35, p = 0.05) in males post-supplementation. In conclusion, VD status correction reduced serum NOx, particularly in males. The inhibition of NOx synthesis may be responsible for the anti-inflammatory effects of VD supplementation. An inverse association was found between NOx and CPN2.

Acute Glycemic Control in Prediabetes Individuals Favorably Alters Serum NLRP3 Inflammasome and Related Interleukins.

Hyperglycemia associated with prediabetes (PD) alters NLRP3 inflammasome activity and related interleukins, yet no study has evaluated the expression of the NLRP3 inflammasome complex and related interleukins in individuals with a PD condition that did or did not develop type 2 diabetes mellitus (T2DM). This study investigated the effect of 6 months of lifestyle modification on the expression of the NLRP3 inflammasome and related interleukins (1α, 1ß, 18, 33 and 37) in the sera of individuals with a PD condition that did or did not develop T2DM. This interventional study included 67 Saudi adults (mean age = 41.9 ± 8.0 years, mean BMI = 33.2 ± 5.5 kg/m2). Overnight-fasting serum samples were collected at baseline and at the 6-month follow-up. Serum levels of NLRP3, capsase-1 and related ILs were analyzed at both visits using commercially available immunoassay kits. Results showed that IL-1α increased in the PD group that developed T2DM (p = 0.046), IL-33 decreased in the PD group that reverted to normal (p < 0.001) and NLRP3 decreased in the PD group that remained PD (p = 0.01). Results also showed a positive over-time correlation between NLRP3 and both IL-1α and IL-33 (p < 0.001 and p = 0.028, respectively). In conclusion, glycemic control favorably altered NLRP3 inflammasome complex activity, and lifestyle modification in PD individuals is crucial in reversing harmful metabolic and inflammatory phenotypes.

Cardiometabolic associations of circulating Lipocalin-2 in adults with varying degrees of adiposity and insulin resistance.

Lipocalin (Lcn2) acts as a mediator of several inflammatory processes. However, evidence on the role of Lcn2 in regulating adiposity and type 2 diabetes mellitus (T2DM) is scarce. Therefore, our study aimed to evaluate the associations between Lcn2 and cardiometabolic parameters among Arab adults with varying degrees of adiposity and insulin resistance. A total of 819 adult Saudi participants (307 males and 512 females) with and without T2DM were included. Anthropometrics, metabolic profile and circulating Lcn2 were assessed. Circulating Lcn2 was significantly highest in the obese group independent of age and sex (p = 0.004), but this significance was lost after stratification to T2DM status. Comparison within age groups revealed that among T2DM participants aged 60-70 years, Lcn2 levels were significantly lower than their younger counterparts in both non-obese and obese groups (unadjusted p = 0.04 and < 0.001, respectively). Lcn2 was inversely associated with diastolic blood pressure (R = -0.25, p = 0.01) and triglycerides (R = 0.23; p = 0.04) as well as positively associated with adiponectin (R = 0.27; p = 0.005) among non-obese, non-T2DM participants. In the T2DM/obese group (N = 328), Lcn2 was inversely associated with age (R = -0.15; p = 0.008) and positively associated with HDL-cholesterol (R = 0.12; p = 0.04) and adiponectin (R = 0.17; p = 0.002). Our study suggests that circulating Lcn2 maybe protective against obesity and T2DM, but prospective studies are needed to confirm findings.

Telomere length and telomere repeat-binding protein in children with sickle cell disease.

BACKGROUND: This study aimed to assess the telomere length and plasma telomere repeat-binding factor 2 (TRF2) levels in addition to other inflammatory markers in children with sickle cell disease (SCD). METHODS: We enrolled 106 children (90 SCD and 26 controls) aged 1-15 years from the Hematology unit of King Fahad Medical City (KFMC), Saudi Arabia. Genomic DNA extracted from blood and leukocyte TL was determined using quantitative reverse transcription PCR, whereas TRF2, C-reactive protein, interleukin-6, and DNA oxidative damage were determined by using respective commercially available assays. RESULTS: Leukocyte TL was inversely correlated with age in the SCD patients (r = -0.24, P = 0.02) and the controls (r = -0.68, P < 0.0001). In addition, SCD patients had significantly shorter TL (7.74 ± 0.81 kb) (P = 0.003) than controls (8.28 ± 0.73 kb). In contrast, no significant difference in TL among the SCD genotypes (HbSS and HbSß0) has been observed. A modest, positive correlation was seen between TL and reticulocyte % (r = 0.21; P = 0.06). There were no significant differences in the TL and TRF2 concentrations between subjects with HbSS and HbSß0 genotypes. CONCLUSIONS: Short leukocyte TL was significantly associated with SCD. An inverse association was observed between TL and hemoglobin. Hydroxyurea treatment revealed no impact on TL. IMPACT: This study explored the TL and plasma TRF2 in Saudi children with SCD. This is the first documentation that SCD children have shorter TL than their healthy counterparts, and no association between TL and TRF2 has been observed. Hydroxyurea treatment showed no impact on TL in children with SCD. This study is the first of its kind in children with SCD. It will pave the way for another study with a larger sample size in a diverse population to scrutinize these findings better.

Primary hyperparathyroidism in Saudi Arabia revisited: a multi-centre observational study.

PURPOSE: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and remains understudied within the Arabian population. The present study, the largest of its kind within the Gulf Cooperation Council (GCC) countries, aims to determine the demographics and clinical presentation of PHPT in Saudi Arabia. METHODS: In this multi-center retrospective study involving three tertiary hospitals in different geographic locations of Saudi Arabia namely, Riyadh, Al Ahsa and Jeddah, a total of 205 out of 243 confirmed PHPT cases aged 16 to 93 years old were included (N = 96 from Riyadh; N = 59 from Al Ahsa and N = 50 from Jeddah). Demographics, clinical manifestations and surgical outcomes were recorded as well as laboratory and radiologic investigations including serum parathyroid hormone (PTH), 25(OH)D, adjusted calcium, estimated glomerular filtration rate (eGFR) and nuclear scan outcome. RESULTS: PHPT cases appeared to increase over time when compared to other local studies published so far, with 12.8 cases per 100,000 hospital population. Females outnumber males (3:1) with 86% seen as out-patients. The average age was 59.8 ± 15.5 years. Abnormal PTH scan was seen in 171 patients (83.4%). Kidney stones was the most common renal manifestation (32 cases, 15.6%) and osteoporosis was the most common skeletal manifestation (67 cases, 32.7%). Al Ahsa had the highest prevalence of multiple comorbidities at 54% and the highest prevalence of obesity as a single comorbidity (17%) compared to other regions (p < 0.05). Jeddah recorded the highest prevalence of osteoporosis with bone and joint pains (30%) (p < 0.05). CONCLUSION: Comparison of present data with previous local studies suggest an increasing trend in PHPT cases in Saudi Arabia. Regional variations in the clinical presentation of PHPT were observed and warrant further investigation.

-2548G>A LEP Polymorphism Is Positively Associated with Increased Leptin and Glucose Levels in Obese Saudi Patients Irrespective of Blood Pressure Status

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6−8.4), p = 0.001; 3.2 (1.2−8.6), p = 0.03; 3.5 (1.6−7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2−3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.

Associations of Bone Mineral Density with RANKL and Osteoprotegerin in Arab Postmenopausal Women: A Cross-Sectional Study.

Background and objective: There is limited information as to the association of several key bone markers with bone mineral density (BMD) in understudied ethnic groups. This study investigated the relationship between circulating levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) with BMD in Arab postmenopausal women. Materials and methods: In this cross-sectional study, a total of 617 Saudi postmenopausal women from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases were included. Anthropometric data, BMD, and biochemical data were retrieved from the registry. Participants were stratified into three groups based on T-score; n = 169 with osteoporosis, n = 282 with osteopenia, and n = 166 normal. Analysis of bone markers including RANKL, OPG, osteocalcin, and N-terminal telopeptide (NTx) was completed using commercially available bioassays. Results: The results suggested that OPG was significantly and positively correlated with age in the osteoporosis group (r = 0.29, p < 0.05), while it was inversely correlated with BMD femoral neck left (r = −0.56, p < 0.001) and BMD femoral neck right (r = −0.37, p < 0.05) in the same group. Moreover, RANKL showed a significant inverse correlation with NTx in the osteopenia group (r = −0.37, p < 0.05). Furthermore, the RANKL/OPG ratio had a positive and significant correlation with BMI (r = 0.34, p < 0.05), BMD femoral neck left (r = 0.36, p < 0.05) and BMD femoral neck right (r = 0.35, p < 0.05) in the osteopenia group. By contrast, it showed a significant inverse correlation with waist to hip ratio in the osteoporosis group (r = −0.38, p < 0.05). Multiple regression analysis showed that OPG contributes to BMD variations in the osteopenia group (p = 0.03). Conclusions: In conclusion, changes in circulating levels of RANKL and OPG might be a protective mechanism contrary to the increased bone loss in postmenopausal women.

Vitamin D Receptor Gene Variants Susceptible to Osteoporosis in Arab Post-Menopausal Women.

Post-menopausal osteoporosis (PMO) is a multifactorial bone disorder in elderly women. Various vitamin D receptor (VDR) gene variants have been studied and associated with osteoporosis in other populations, but not in a homogenous Arab ethnic group. Herein, the current study explores the association between VDR polymorphisms and susceptibility to osteoporosis in Saudi postmenopausal women. In total, 600 Saudi postmenopausal women (N = 300 osteoporosis; N = 300 control) were genotyped for VDR gene variants (rs7975232, rs1544410, rs731236) using TaqMan® SNP genotyping assays. Bone mineral density (BMD) for the lumbar spine and femur was assessed using dual-energy X-ray absorptiometry (DEXA). The heterozygous frequency distributions AC of rs7975232, CT of rs1544410, and AG of rs731236 were significantly higher in the osteoporosis group than controls (p < 0.05). Heterozygous AC of rs7975232 (1.6; 95% CI 1.1-2.3; p < 0.023), CT of rs1544410 (1.6; 95% CI 1.1-2.4; p < 0.022), and AG of rs731236 (1.6; 95% CI 1.1-2.4; p < 0.024) were significantly associated with increased risk of osteoporosis, independent of age and BMI. In conclusion, VDR gene variants rs7975232, rs1544410, rs731236 had a significant effect on BMD and were associated with osteoporosis risk in Saudi postmenopausal women.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study.

OBJECTIVES: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. METHODS: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. RESULTS: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity. CONCLUSIONS: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Difference on the prevalence, patterns and awareness of soft drink consumption among male and female Arab students.

BACKGROUND: The increase in soft drink (SD) consumption is emerging as a serious health issue. Our aim is to explore the prevalence and awareness regarding SD consumption among Saudi students. METHODS: This cross-sectional study included 1000 apparently healthy Saudi students (527 males, 473 females) aged 16-23 years. A designed questionnaire including various sections was used to obtain the required information. RESULTS: The BMI and frequency of SD consumption were significantly higher in males (P < 0.001) than females, whereas, females exhibited higher awareness and knowledge regarding SD consumption than males. The SD consumption in females was due to society, taste, availability and markets, whereas in males it was due to cheap price. Females support the implementation of new policies to prevent consumption of SD. CONCLUSIONS: Arab students exhibited a high prevalence of SD consumption especially in males. Although females showed more awareness and knowledge about SD, various misconceptions were notable in both sexes. New policies, health promotion campaigns must be organized to raise awareness among children and parents. Parents and health educators should motivate and encourage the children to consume more water in the context of a healthy balanced diet.

Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country.

PURPOSE: As the world continues to cautiously navigate its way through the coronavirus disease 2019 (COVID-19) pandemic, several breakthroughs in therapies and vaccines are currently being developed and scrutinized. Consequently, alternative therapies for severe acute respiratory coronavirus 2 (SARS-CoV-2) prevention, such as vitamin D supplementation, while hypothetically promising, require substantial evidence from countries affected by COVID-19. The present retrospective case-control study aims to identify differences in vitamin D status and clinical characteristics of hospitalized patients screened for SARS-CoV-2, and determine associations of vitamin D levels with increased COVID-19 risk and mortality. METHODS: A total of 222 [SARS-CoV-2 (+) N = 150 (97 males; 53 females); SARS-CoV-2 (-) N = 72 (38 males, 34 females)] out of 550 hospitalized adult patients screened for SARS-CoV-2 and admitted at King Saud University Medical City-King Khalid University Hospital (KSUMC-KKUH) in Riyadh, Saudi Arabia from May-July 2020 were included. Clinical, radiologic and serologic data, including 25(OH)D levels were analyzed. RESULTS: Vitamin D deficiency (25(OH)D < 50 nmol/l) was present in 75% of all patients. Serum 25(OH)D levels were significantly lower among SARS-CoV-2 (+) than SARS-CoV-2 (-) patients after adjusting for age, sex and body mass index (BMI) (35.8 ± 1.5 nmol/l vs. 42.5 ± 3.0 nmol/l; p = 0.037). Multivariate regression analysis revealed that significant predictors for SARS-CoV-2 include age > 60 years and pre-existing conditions (p < 0.05). Statistically significant predictors for mortality adjusted for covariates include male sex [Odds ratio, OR 3.3 (95% confidence interval, CI 1.2-9.2); p = 0.02], chronic kidney disease [OR 3.5 (95% CI 1.4-8.7); p = 0.008] and severe 25(OH)D deficiency (< 12.5 nmol/l), but at borderline significance [OR 4.9 (95% CI (0.9-25.8); p = 0.06]. CONCLUSION: In hospital settings, 25(OH)D deficiency is not associated with SARS-CoV-2 infection, but may increase risk for mortality in severely deficient cases. Clinical trials are warranted to determine whether vitamin D status correction provides protective effects against worse COVID-19 outcomes.

Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study.

BACKGROUND: Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap. METHODS: In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed. RESULTS: A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7-5.3); p < 0.001], congestive heart failure [adjusted HR 3.5 (CI 1.4-8.3); p = 0.006], smoking [adjusted HR 5.8 (CI 2.0-17.2); p < 0.001], ß-blocker use [adjusted HR 1.7 (CI 1.0-2.9); p = 0.04], bilateral lung infiltrates [adjusted HR 1.9 (CI 1.1-3.3); p = 0.02], creatinine > 90 µmol/l [adjusted HR 2.1 (CI 1.3-3.5); p = 0.004] and 25(OH)D < 12.5 nmol/l [adjusted HR 7.0 (CI 1.7-28.2); p = 0.007] were significant predictors of mortality among hospitalized Covid-19 patients. Random blood glucose ≥ 11.1 mmol/l was significantly associated with intensive care admission [adjusted HR 1.5 (CI 1.0-2.2); p = 0.04], as well as smoking, ß-blocker use, neutrophil > 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l. CONCLUSION: The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, ß-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.

The association between iron and vitamin D status in Arab adolescents.

OBJECTIVE: Both vitamin D and Fe micronutrient deficiencies are common in Saudi Arabia but the association between them is unclear. The present study aimed to determine whether Fe indices are associated with vitamin D status and other metabolic markers in Arab adolescents. DESIGN: Single-centre, cross-sectional study gathering anthropometrics, glucose and lipid profile. Serum 25-hydroxyvitamin D (25(OH)D), Fe, total iron-binding capacity (TIBC), transferrin saturation (%) and other parameters were measured. SETTING: Vitamin D School Project Database, King Saud University (2014-2016). PARTICIPANTS: Arab adolescents aged 10-17 years randomly selected from the Vitamin D School Project Database (170 Saudi students; 100 girls, seventy boys). RESULTS: Among Fe indices, only TIBC was found to be significantly and inversely associated with 25(OH)D (r = -0·20; P < 0·01) and only in girls (r = -0·20; P < 0·05). Among cardiometabolic parameters, serum Fe was associated with TAG in boys (r = 0·36; P < 0·01) and inversely associated with HDL-cholesterol in girls (r = -0·29; P < 0·05). Age was the most significant predictor of serum Fe for all participants, accounting for 5 % (R2 = 0·05; P = 0·004) of variance perceived. Serum 25(OH)D and age, on the other hand, were the most significant predictors for TIBC, accounting for 10·1 % (R2 = 0·10; P < 0·001) of variance perceived. CONCLUSIONS: Among healthy Arab adolescents, the association between vitamin D and Fe indices, particularly TIBC, is modest, inverse and sex-dependent. Larger studies with inclusion of markers such as hepcidin and ferritin, vitamin D metabolites and endogenous sex hormones may provide a clearer view of this complex association.