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Background: In the wake of the warning by WHO that the prevalence of dementia may have a rise of 125% in the Middle East by 2050, identification of the genetic risk factors in Arab populations is urgent. Objective: To investigate the association of Single Nucleotide Polymorphisms (SNPs) in apolipoprotein E (ApoE), clusterin (CLU), tumor necrotic factor- α (TNF-α) and interleukin-6 (IL-6) genes, with risk of Alzheimer’s disease (AD) in Saudi Arabian participants. Method: A total of 42 Saudi AD patients and 23 age-matched control participants were genotyped for eight SNPs: rs429358, rs7412 (ApoE); rs11136000, rs1532278 (CLU); rs1800629, rs1799724 (TNF-α) and rs1800796, rs1800795(IL-6), by RT-PCR using the TaqMan assay. Serum concentrations of amyloid beta peptide 1–40(Aβ1-40), amyloid beta peptide 1–42(Aβ1- 42), CLU and some other biochemical markers were measured. Results: A significant increase (p=0.004) in the serum CLU level was detected in the AD group (340.4 ± 74.6) compared with control group (265.0 ± 80.9). For rs1532278 (CLU), genotype GA was significantly higher in AD patients (57.1%) than in the control participants (26.1%), [p=0.024, OR = 4.00, 95% CI (1.20-13.28)]. For the ApoE SNP rs7412, 40.4% of patients carried a TT genotype, whereas it was completely absent in the controls [p = 0.020, OR = 30.53, 95% CI (1.73 – 540.05)].For rs429358 (ApoE), patients showed a significantly increased frequency of the TC genotype [p = 0.006, OR = 9.33, 95% CI (1.89–46.19)] and TT [p = 0.045, OR = 19.76, 95% CI (1.07–366.0)] genotype than controls. AD patients with CC genotype for ApoE rs429358 had significantly lower levels of Aβ1-40 (p=0.04) in AD patients than controls. Carriers of genotype GG for rs1800629 (TNF-α) showed significantly higher levels of serum IL-6 (p = 0.04) in AD patients. Conclusion: Genetic variants in ApoE and CLU may influence susceptibility to AD among Saudi Arabian participants.

Summary The Saudi Osteoporosis Society (SOS) has updated its guidelines for the diagnosis and management of osteoporosis in Saudi Arabia (SA), with emphasis on postmenopausal women. This document is relevant to all healthcare professionals in SA involved in the care of patients with osteoporosis and osteoporosis-related fractures. Introduction The SOS launched the first national osteoporosis guidelines in 2015 and spearheaded the Gulf Cooperation Council Countries (GCC) osteoporosis consensus report in 2020 which was under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO). This paper highlights a major update of the guidelines in the SA setting. Methods This guideline is an adaptation of the current guidelines derived from ESCEO, the American Association of Clinical Endocrinologists (AACE), and the GCC osteoporosis consensus report and studies on osteoporosis done in SA. Where accessible, the timeliest systematic review, meta-analysis, and randomized controlled trials were used as evidence. Results The present update includes new recommendations for the assessment of osteoporosis taking into consideration the Saudi model of FRAX for fracture probabilities, appropriate doses for the maintenance of vitamin D status and calcium, the use of representative blood analytes for therapy monitoring, the use of romosozumab and sequential therapy in the pharmacological management strategies, and the establishment of fracture liaison services to prevent secondary fractures. Conclusion This updated guideline is for all healthcare professionals involved in osteoporosis and post-fracture care and management in SA and harmonized the most up-to-date changes in the field based on evidence-based medicine for use in the local setting.

Inflammasome activation of the nucleotide-binding domain, leucine-rich–containing family, and pyrin domain–containing-3 (NLRP3) has been observed to be involved in the pathogenesis of numerous inflammatory diseases, including prediabetes (PD) and type 2 diabetes mellitus (T2DM). Varying levels of glycemia can trigger inflammasome activation; yet, limited studies have reported the associations between NLRP3 levels or other circulating interleukins (ILs) and glycemic status. This study investigated the differences and associations between serum levels of NLRP3 and IL-1α, IL-1β, IL-33 and IL-37 in Arab adults with PD and T2DM. A total of 407 Saudi adults (151 males and 256 females) (mean age = 41.4 ± 9.1 years and mean BMI = 30.7 ± 6.4 kg/m2) were included. Overnight-fasting serum samples were collected. The participants were stratified according to T2DM status. Serum levels of NLRP3 and ILs of interest were assessed using commercially available assays. In all participants, age- and BMI-adjusted circulating levels of IL-37 were significantly higher in the T2DM group (p = 0.02) than in healthy controls (HC) and the PD group. A general linear model analysis revealed that NLRP3 levels were significantly influenced by T2DM status; age; and ILs 18, 1α and 33 (p-values 0.03, 0.04, 0.005, 0.004 and 0.007, respectively). IL-1α and triglycerides significantly predicted NLRP3 levels by as much as 46% of the variance perceived (p < 0.01). In conclusion, T2DM status significantly influenced NLRP3 expression and other IL levels in varying degrees. Whether these altered levels of inflammasome markers can be favorably reversed through lifestyle interventions needs to be investigated prospectively in the same population.

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.

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 r = 0.44 p r = -0.18, p = 0.001). The correlations between the Arabic and the English SBQ versions ranged from 0.25–0.96; p p th 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.

The Single Point Insulin Sensitivity Estimator (SPISE) is a novel surrogate marker for insulin sensitivity and was found comparable to the gold standard clamp test as well as for predicting the Metabolic Syndrome (MetS) in several populations. The present study aimed to assess for the first time, the validity of SPISE in predicting MetS among Arab adolescents. In this cross-sectional study, 951 Saudi adolescents aged 10–17 years were randomly recruited from different schools across Riyadh, Saudi Arabia. Anthropometrics were measured and fasting blood samples were collected for the assessment of glucose, lipid profile, adipokines, C-reactive protein and 25 hydroxyvitamin (OH) D. MetS was defined using the National Cholesterol Education Program’s (NCEP) criteria with age-specific thresholds for adolescents. The SPISE as well as insulin resistance (HOMA-IR) indices were calculated. The over-all prevalence of MetS was 8.6% (82 out of 951). SPISE index was significantly lower in MetS than non-MetS participants in both sexes (5.5 ± 2.5 vs. 9.4 ± 3.2, p < 0.001 in boys and 4.4 ± 1.4 vs. 8.6 ± 3.2, p < 0.001 in girls). The SPISE index showed a significant inverse correlation with resistin, leptin, and C-reactive protein, and a significant positive correlation with adiponectin and 25(OH) D. Areas under the curve (AUC) revealed fair and good accuracy for predicting MetS 84.1% and 90.3% in boys and girls, respectively. The sex-specific cut-off proposed was SPISE index ≤6.1 (sensitivity 72.2% and specificity 83.9%) for boys and ≤6.46 (sensitivity 96.3% and specificity 73.4%), for girls. This study suggests that the SPISE index is a simple and promising diagnostic marker of insulin sensitivity and MetS in Arab adolescents.

Polyphenols may modulate gut microbiota; however, limited studies have examined this relationship relative to obesity. We aim to investigate the association between polyphenol intake and gut microbiota composition in relation to obesity indices among Saudi Arabian females. This study included 92 adults stratified by body mass index (BMI) into controls (BMI ≥ 18.5–24.9 kg/m2; n = 48) and cases (BMI ≥ 30.0 kg/m2; n = 44), and further divided into high and low polyphenol intake by median intake (252 mg/1000 kcal/day). Fecal samples were collected to analyze the gut microbiota composition via the whole-genome shotgun sequencing technique. Results showed that Flavonifractor plautii and Clostridium bolteae were positively correlated with polyphenol intake in the total sample (r = 0.22, p = 0.03; r = 0.28, p = 0.01, respectively). There were inverse correlations between Blautia wexlerae and polyphenol intake (r = −0.56, p < 0.01) in the case group, and between Bacteroides thetaiotaomicron and polyphenol intake (r = −0.45, p = 0.03) in the control group. Those in the case group with low polyphenol intake, and those with high waist-to-hip ratio (WHR; ≥0.83), showed significantly lower alpha-diversity than those in the control group with normal WHR (

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 &lt, 0.05). Heterozygous AC of rs7975232 (1.6, 95% CI 1.1–2.3, p &lt, 0.023), CT of rs1544410 (1.6, 95% CI 1.1–2.4, 0.022), and AG of rs731236 (1.6, 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.

Several studies have found a correlation between inflammatory markers and sarcopenia; however, limited research has been conducted on the Arabic population. Therefore, this study aimed to investigate the value of inflammatory parameters in Saudi elderly women with sarcopenia. In this cross-sectional study, 76 elderly Saudi women (>65 years) were stratified according to the presence (n = 26) or absence (n = 50) of sarcopenia, using the operational definition of the Asian Working Group for Sarcopenia (AWGS). Demographics and clinical data were collected. Muscle mass, muscle strength, and physical performance were assessed using bioelectrical impedance, hand grip and timed-up-and-go (TUG) tests, respectively. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) were assessed using commercially available assays. Muscle mass and strength indicators were lower in the sarcopenia group (p-value < 0.05). Moreover, interleukin 6 (IL-6) was positively correlated with TUG (r = 0.48, p-value < 0.05), while CRP showed an inverse correlation with the right leg muscle (R-Leg-M) and a positive correlation with triceps skinfold (TSF) (r = −0.41, r = 0.42, respectively, p-values < 0.05). Additionally, TSF and R-Leg-M were independent predictors of CRP variation (R2 = 0.35; p < 0.01). Lastly, participants with a TNF-α > 71.2 were five times more likely to have sarcopenia [(OR = 5.85), 95% CI: 1.07–32.08; p = 0.04]. In conclusion, elevated levels of TNF-α are significantly associated with the risk of sarcopenia, while variations perceived in circulating CRP can be explained by changes in the muscle mass indices only among individuals with sarcopenia. The present findings, while promising, need further investigations on a larger scale to determine whether inflammatory markers hold any diagnostic value in assessing sarcopenia among elderly Arab women.

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/., Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

Type 2 diabetes mellitus (T2DM) is a multifactorial non-communicable disease that is characterized by insulin resistance and chronic sub-clinical inflammation. Among the emerging inflammatory markers observed to be associated with β-cell damage is interleukin 1β (IL1β), a proinflammatory cytokine that modulates important metabolic processes including insulin secretion and β-cell apoptosis. The present systematic review and meta-analysis gathers available evidence on the emerging role of IL1β in T2DM. PubMed and Embase were searched for human studies that assessed 1L1β in T2DM individuals from 2016-2021. Thirteen studies (N=2680; T2DM=1182, controls=1498) out of 523 were included in the systematic review and only 3 studies in the meta-analysis. Assays were the most commonly used quantification method and lipopolysaccharides as the most common stimulator for IL1β upregulation. Random and fixed effects meta-analysis showed non-significant mean differences of IL1β concentrations between the T2DM and controls. Given the high heterogeneity and small subset of studies included, caution is advised in the interpretation of results. The present systematic review and meta-analysis highlights the limited evidence available that could implicate 1L1β as a potent biomarker for T2DM. Standardization of 1L1β assays with larger sample sizes are encouraged in future observational and prospective studies.

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 p 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.

Existing literature on the association between influenza vaccination and COVID-19 infection/outcomes is conflicting. Therefore, we aimed to investigate the association between influenza vaccination and COVID-19 outcomes in a large cohort of adults who participated in the SHARE (Survey of Health, Ageing, and Retirement in Europe). Information regarding influenza vaccination in the previous year, and medical and demographic characteristics, were self-reported. Positivity for COVID-19, symptomatology, and hospitalization were also ascertained using self-reported information. An adjusted logistic regression analysis (including 15 baseline factors or propensity score) was used to assess the association between influenza vaccination and COVID-19 outcomes. A total of 48,408 participants (mean age 67 years; 54.1% females) were included. The prevalence of influenza vaccination was 38.3%. After adjusting for 15 potential confounders, influenza vaccination was significantly associated with a lower risk of positivity for COVID-19 (OR = 0.95; p < 0.0001), symptomatic forms (OR = 0.87; p < 0.0001), and hospitalization for COVID-19 (OR = 0.95; p < 0.0001). The results were similar when using a propensity score approach. In conclusion, influenza vaccination may be beneficial for the prevention of COVID-19, as the present study found that influenza vaccination was associated with a small/moderate lower risk of COVID-19 infection and adverse outcomes.

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.

Since their inception in the commercial market in the mid-twentieth century, sulfonylureas (SUs) have remained a therapeutic option in the management of type 2 diabetes (T2D). Despite their established glucose-lowering effects, there is no consensus among global experts and modern guidelines regarding the priority of SUs in relation to other therapeutic options, given the lack of evidence that SUs are associated with a low risk of macrovascular events and excess mortality. However, findings from recent trials and real-time observations have resolved this contentious issue somewhat, albeit to varying degrees. The present consensus discusses the role of SUs in contemporary diabetes management in the Gulf Cooperation Council (GCC) countries. Regional experts from these countries gathered virtually to formulate a consensus following presentations of topics relevant to SU therapy with an emphasis on gliclazide, including long-term efficacy, cost, end-organ benefits, and side effects, based on up-to-date evidence. The present narrative review reflects the conclusions of this assembly and provides a platform upon which future guidelines for the use of SUs in the GCC can be tailored.

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 P = 0.003) than controls (8.28 ± 0.73 kb). In contrast, no significant difference in TL among the SCD genotypes (HbSS and HbSβ0) 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 HbSβ0 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.

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 60 years and pre-existing conditions (p

Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer’s disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.

Objective. To examine differences in maternal serum levels of adipokines (adiponectin, leptin, and resistin) and inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6)) from early to midpregnancy among Arab women with or without gestational diabetes mellitus (GDM), along with their links to GDM risk. Methods. This is a multicenter prospective study involving 232 Saudi women attending obstetric care. Both circulating adipokine and markers of inflammation were observed at the first (eight to 12 weeks) and second trimesters (24 to 28 weeks). GDM was screened at 24 to 28 weeks using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results. Age and body mass index- (BMI-) matched circulating TNF-α was significantly higher in women with GDM in comparison to non-GDM women ( p = 0.01 ). Adiponectin and resistin significantly decreased from the first to second trimester in women without GDM ( p = 0.002 and 0.026, respectively). Leptin presented a significant rise from the first to second trimester in both groups, with a higher increase in women with GDM ( p = 0.013 ). Multivariate logistic regression analysis revealed that TNF-α was significantly correlated with GDM ( p = 0.03 ). However, significance was lost after adjustments for maternal and lifestyle risk factors (OR 23.58 (0.50 to 1119.98), p = 0.11 ). Conclusion. Inflammatory and adipocytokine profiles are altered in Arab women with GDM, TNF-α in particular. Further studies are needed to establish whether maternal inflammatory and adipocytokine profile influence fetal levels in the same manner.

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 90 µmol/l [adjusted HR 2.1 (CI 1.3–3.5); p = 0.004] and 25(OH)D 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, β-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.

Sarcopenia is the loss of skeletal muscle mass, and is most common in older people. The present multi-center cross-sectional study aimed to determine the prevalence of sarcopenia and possible risk factors among Arab elderly females. A total of 131 ambulatory Saudi elderly females aged 60–85 years (mean age 65.9 ± 5.5 years) were recruited to participate. A general questionnaire with questions related to sociodemographic factors, medical history, diet, physical activity, and lifestyle was administered. Anthropometrics and muscle assessments were done. Fasting blood glucose and lipids were measured routinely. Circulating 25(OH)D and irisin levels were measured using commercially available assays. Sarcopenia was assessed using the criteria of the Asian Working Group for Sarcopenia (AWGS). Over-all prevalence of sarcopenia was 19.8% (26 out of 131 participants). Novel measures such as abdominal volume index (AVI), dietary fiber, and irisin were found to be significantly lower in the sarcopenia group than those without sarcopenia, independent of age. No associations were found with physical activity or dietary and lifestyle habits. In conclusion, sarcopenia is relatively common among Arab elderly females. Longitudinal studies are needed to determine whether lifestyle modifications can decrease the incidence of sarcopenia in this population. Irisin maybe a promising biomarker for sarcopenia but needs to be confirmed using larger sample sizes.

Type 2 diabetes mellitus (T2DM) outcomes were observed to be influenced by circulating trace elements' status. The differences and correlations between serum levels of chromium (Cr), manganese (Mn), nickel (Ni), and selenium (Se) in Saudi patients with and without T2DM as well as those with prediabetes (pre-DM) were examined in this retrospective cross-sectional study.Anthropometrics and fasting blood samples were collected from 119 patients with T2DM (aged 41-64 years), 95 non-T2DM (aged 27-55 years), and 80 with pre-DM (aged 35-57 years). An inductively coupled plasma-mass spectrometer was used to measure trace minerals in the blood.T2DM patients had significantly lower Mn serum concentrations than controls. There was no difference in Cr and Ni levels between groups. Serum Mn and Ni levels were lower in pre-DM subjects than controls. Serum Se concentrations were higher in pre-DM and T2DM patients than controls. In T2DM patients, serum Cr and Mn levels were inversely correlated with glucose, while Ni and Se levels were positively correlated with glucose in the T2DM group.Because of their roles in glucose metabolism, impaired trace element status may also play a role in T2DM pathogenesis. Appropriate dietary control and mineral supplementation are recommended.

ObjectiveWe aimed to evaluate and compare the impact of COVID-19 lockdown on lifestyle changes and other common related effects of the lockdown in Saudi adults with diabetes mellitus (DM), both type 1 (T1D) and type 2 diabetes (T2D).Methods265 T1D and 285 T2D individuals were included in this cross-sectional survey during lockdown using an online questionnaire and compared with 297 participants without DM. Variables included demographics, treatment changes, use of supplements, change in sleeping habits and physical activity, dietary changes, social and mental health, and education and awareness during COVID-19 lockdown.ResultsThe COVID-19 lockdown was associated with more treatment doses in people with T1D but not in those with T2D (p = 0.003). More participants with T1D and T2D than the control group reported that they felt symptoms of depression during lockdown (ORs of 1.83, p = 0.008 and 2.2, p = 0.001, respectively) and that lockdown affected them psychologically (ORs of 1.64, p = 0.019 and 1.85, p = 0.005, respectively). More participants with T1D than controls reported that their physical activity decreased during lockdown (OR of 2.70, p = 0.024). Furthermore, significantly lesser participants in both DM groups than controls agreed that the health education regarding COVID-19 covered everything (ORs of 0.41, p < 0.001 and 0.56, p < 0.001, respectively for T1D and T2D groups). Regarding dietary habits, the DM groups reported more changes in either the number of daily meals, meal content, or mealtimes than the control group.ConclusionsCOVID-19 lockdown-associated lifestyle changes were more prevalent in individuals with T1D and T2D compared to control. Findings may assist public health authorities in outlining their responses in pandemics and promote healthy lifestyle adaptations in this high-risk cohort to limit adverse effects in future lockdowns.

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people.

This 12-month school-based intervention study investigated the effects of hybrid educational lifestyle modifications on glycemic control among Saudi youth with different glycemic statuses. A total of 2600 Arab adolescents aged 12–18 years were recruited from 60 randomly selected schools. Anthropometrics, blood glucose, and HbA1c were measured pre- and post-intervention. Participants were grouped according to baseline HbA1c into normal, prediabetes, and diabetes groups. All participants received lifestyle education at base line and at every 3-month interval to improve diet and exercise behavior. Diabetic and prediabetic participants received a tailored lifestyle intervention. Post-intervention, 643 participants were analyzed as follows: 20 participants from the diabetes group, 39 from prediabetes, and 584 from the normal group. A modest but significant improvement in the glycemic status of diabetic and prediabetic participants was observed, but not in the normal group. In the diabetes group, 11 (55%) participants achieved normal HbA1c levels, 5 had prediabetes levels, and only 4 remained within diabetes HbA1c levels. In the prediabetes group, 34 (87.2%) participants achieved normal HbA1c levels, while 2 (5.1%) participants remained prediabetic and 3 (7.7%) had diabetes HbA1c levels (p < 0.001). This hybrid lifestyle intervention program modestly reduces the risk of T2DM among youth with elevated HbA1c levels. The challenge of sustaining interest in adopting lifestyle changes for a longer duration should be addressed in further studies in this population.

BackgroundChildhood obesity and pediatric metabolic syndrome (MetS) have steadily increased during the last decade in Saudi Arabia. Intervention programs to prevent cardiometabolic disorders in Arab youth are needed.ObjectiveIn this multi-school intervention study which was disrupted by COVID-19-imposed lockdowns (September 2019–April 2021), a 12-month lifestyle education program focused on improving the cardiometabolic status of Arab adolescents was investigated.MethodsA total of 2,677 Saudi students aged 12–18 years were recruited from 60 different secondary and preparatory year schools in Riyadh city, Saudi Arabia. The intervention was initially in-person counseling sessions and the subsequent sessions conducted virtually post-pandemic. Baseline anthropometrics and fasting blood samples for glucose, HbA1c, and lipid assessments were collected at baseline and after 12 months (704 participants).ResultsOnly 704 out of 2,677 (73.7% dropout) completed the intervention. At baseline, 19.6% of the participants were overweight and 18.1% were obese. A modest but significant decrease in the prevalence of central obesity [11.2 vs. 6.7% (−4.5% change, p = 0.002)], hypertension [22.3 vs. 11.4% (−10.9% change, p < 0.001)], and low-HDL cholesterol [61.6 vs. 23.3% (−38.3% change, p < 0.001)] was noted. Consequently, the prevalence of hypertriglyceridemia increased from 22.7 to 56.3% (+ 33.6%, p < 0.001) overtime. Also, the proportion of subjects who were able to change their status from MetS to non-MetS was significantly more in overweight/obese at baseline than normal weight (16.9 vs. 3.6%, adjusted OR = 3.42, p < 0.001).ConclusionInterrupted lifestyle education programs secondary to COVID-19-imposed lockdowns still provided modest effects in improving cardiometabolic indices of Arab adolescents. Given the high digital literacy of Arab youth, improving the delivery of virtual lifestyle education programs may prove beneficial.

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 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.

Introduction Type 1 diabetes mellitus (T1DM) is on the rise in Saudi Arabia. Management of T1DM is crucial in curbing the economic burden of this disease. Studies on insulin pump issues are scarce in the region. The present study aims to fill this gap. Methods In this single-centre, retrospective study done in King Abdulaziz Medical City (KAMC) from March 2018 to March 2019, a total of 118 known Saudi T1DM adults (34 males and 84 females) were included. Data on demographics, glycated haemoglobin (HbA1c) and CSII use were collected. Results The most common problem encountered by the patients on CSII was breaking down of the pump (30.0%), relocation of the cannula or tubing (22%) and air bubbles affecting delivery (16.1%). Eighty-one subjects (68.6%) claimed to have been admitted for DM management while on CSII. The use of CSII led to a significant reduction in HbA1c in all subjects (p

Low levels of vitamin D have been linked with increased adiposity and diminished muscle strength. Whether it is also related to fat deposition in muscle tissues is not studied well. This study explored the associations between circulating 25-hydroxyvitamin D (25(OH)D) and fat deposition in muscle tissues of adult Arab males. A total 465 adult Saudi males were included in this cross-sectional study. Anthropometrics, body composition and muscle strength were assessed. Serum 25(OH)D was determined and quantified enzymatically. They were grouped according to vitamin D status: deficient (25(OH)D 50 nmol/l)140 (30.1%). Mean level of lean/height2, lean-arm-legs and lean-arms-legs/height2 were significantly higher in 25(OH)D deficient participants (p-values 0.03; 0.05 and 0.01 respectively). Thigh strength was significantly higher in 25(OH)D sufficient participants than their deficient counterparts (p = 0.02). In all participants, a significant correlation between 25(OH)D was observed with age and thigh-strength (p-values

Objective Osteoporosis is a bone disease characterized by bone mass reduction with a prevalence of approximately 34–48% in Saudi Arabia. Many risk factors can increase osteoporosis fracture, including low vitamin K levels. However, its exact role on bone mineral density (BMD) remains under investigated. This study aims to determine whether dietary vitamin K is associated with BMD, inflammation, undercarboxylated osteocalcin (ucOC) and other bone markers among adult Saudi females. Methods A total of 138 Saudi females aged 25 and above were recruited from different primary health care centers in Riyadh, Saudi Arabia, and were divided according to BMD status (N = 53 normal; N = 85 low BMD). Each participant completed a food frequency questionnaire. Anthropometrics were measured and serum 25(OH)D and vitamin K, bone markers (ucOC and CTX) and cytokines (IL-6, TNF-α) were assessed using assays. Results Low dietary vitamin K intakes were observed in both groups, ranging only 16–19 µg/day. A positive association was seen between dietary vitamin K and IL-6 in low BMD group and TNF-α in all participants. No significant association was seen between dietary vitamin K and BMD. Conclusion Dietary vitamin K is significantly associated with inflammation and not BMD in adult Saudi females. The alarmingly low dietary vitamin K intake is worth investigating further.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital., SCOPUS: re.j, info:eu-repo/semantics/published

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

This study aimed to assess the relationship between vitamin D [25(OH)D] status and parathyroid hormone (PTH) in Saudi adults to determine the optimum 25(OH)D cut-off in the Saudi adult population. A total of 1093 apparently healthy Saudi subjects (720 women and 373 men) aged 50.7 ± 13.9 years were included in this cross-sectional study. Serum 25(OH)D, PTH, calcium and albumin levels were determined. The over-all prevalence of 25(OH)D deficiency (

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of ‘alternative’ therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects. Electronic supplementary material The online version of this article (10.1007/s40520-020-01515-1) contains supplementary material, which is available to authorized users.

Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.

Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall −0.34, p

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.

Metabolic syndrome (MetS) is a serious health condition that is becoming extremely threatening in Saudi Arabia. The link between vitamin D receptor (VDR) gene polymorphisms and maternal MetS has been observed in several ethnic groups, but is yet to be clarified in the Arabian population. This study aims to investigate the relationship between the FokI VDR genotype and the risk of MetS and its components in pregnant Saudi women. A cross-sectional study was conducted using 368 pregnant Saudi women on first trimester screened for MetS (44 with MetS and 324 without MetS). Measurements included anthropometrics, glycemic and lipid profile and 25(OH)D. TaqMan genotyping assay was used to determine Fokl VDR genotype of participants. Vitamin D deficiency (25(OH)D FokI VDR genotyping frequencies for FF, Ff, and ff genotypes were 50%, 36.4% and 13.6%, respectively. In controls, the frequencies were 62.7%, 31.4% and 5.9%, respectively. No significant association between the individual MetS components and FokI VDR genotypes were observed. Nevertheless, carriers of the ff allele had a significant risk for full maternal MetS [Odds Ratio 4.2 (95% Confidence Interval 1.4-12.2; adjusted p=0.009). The study suggests that the ff FokI VDR genotype is a genetic marker of maternal MetS in pregnant Arabian women. Prospective studies that include neonatal outcomes may confirm present findings.

The present study aims to investigate the association of the serum levels of Fetuin-A and Fetuin-B with type 2 diabetes mellitus (T2DM) in obese Saudi patients and explore the mechanism that links obesity and T2DM in Saudi patients. In this study, a total of 240 adult Saudis (116 men and 124 women) in the age group of 42.7±11.6 years were divided into three groups based on fasting blood glucose (FBG) levels: controls, T2DM and prediabetic. The levels of FBG, lipid profile and serum insulin were measured. Enzyme-linked immunosorbent assay (ELISA) was done to measure Fetuin-A, Fetuin-B and C-reactive protein (CRP). The results show that participants of the prediabetic and T2DM groups had significantly higher body mass index (BMI) values and elevated blood pressure (BP), FBG, total cholesterol (TC), triglyceride (TG), insulin, homeostatic model assessment-IR (HOMA-IR) and homeostatic model assessment-β (HOMA-β) as compared to the control group (P0.05). When results were segregated according to gender, FBG and HDL-C were significantly elevated (P=0.043 and P=0.002, respectively) in T2DM women (12.6±3.6 mmol/l and 1.0±0.3 mmol/l, respectively) compared to T2DM men (11.0±3.3 mmol/l and 0.86±0.2 mmol/l, respectively). However, the diastolic BP and waist-hip ratio (WHR) were significantly increased (P=0.010 and P=0.006, respectively) in T2DM men. The BMI and TC and all other measured parameters were similar between the two genders. Fetuin-A was significantly and positively associated with insulin levels (R=0.19, P=0.05), HOMA-IR (R=0.25, P=0.01) and TG (R=0.20, P=0.01) among overall participants of this study. The T2DM participants exhibited a significantly positive correlation with body weight. Fetuin-A was significantly and positively correlated with Fetuin-B in prediabetic participants, but this relation was not observed in the T2DM participants. Fetuin-B correlated inversely (P

Nutrition-acquired osteomalacia is a bone mineralization disorder associated with dietary calcium and/or solar vitamin D deficiency, risk factors considered common in the Middle Eastern region. Establishing less invasive, cheap, and widely available diagnostic markers for this underdiagnosed entity is essential, in particular for screening in high-risk groups. This study assessed the prevalence of biochemical osteomalacia in Arab adolescents. In this cross-sectional study performed between September 2019 and March 2021, adolescents aged 12–17 years from 60 different secondary and preparatory year schools in Riyadh, Saudi Arabia were included. Anthropometrics and fasting blood samples were collected. Biochemical osteomalacia was defined as any two of the following four serum markers of hypomineralization, namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high alkaline phosphatase (ALP), low calcium (Ca), and/or inorganic phosphorous (Pi). A total of 2938 Arab adolescents [1697 girls; mean age (years) 14.8 ± 1.8; 1241 boys; mean age 15.1 ± 1.6] were recruited. Vitamin D deficiency was noted in 56.2% (n = 953) of girls and 27.1% (n = 336) of boys (p < 0.001). The overall prevalence of biochemical osteomalacia was 10.0% (n = 295/2938) and was higher in girls than boys (14.7% vs. 3.6%, p < 0.001). The prevalence of low serum Ca and/or Pi was also higher in girls than in boys (24.2% vs. 12.5%, respectively, p < 0.001), as well as elevated ALP (5.1% vs. 1.5%, p < 0.001). Overall, girls were 4.6 times (95% CI 3.3–6.4) more likely to have biochemical osteomalacia than boys. Screening of apparently healthy Arab adolescents revealed a high prevalence of deranged mineralization markers suggestive of biochemical osteomalacia, which was significantly more common in girls than boys and was likely associated with Arab traditional clothing and diet. The proposed combination of typically altered mineralization markers for the diagnosis of osteomalacia is, at best, suggestive until further comparisons with established diagnostic tools (histological analysis of bone biopsies) are conducted.

Diabetes mellitus (DM) is a major health issue in Saudi Arabia. Prevention of DM and its complications requires an understanding of the disease and modifiable behaviors (e.g., physical activity—PA). The purpose of this study was to examine the trends in knowledge of the general population regarding DM to better understand the shortcomings in the current awareness programs. This article presents a cross-sectional series study where a survey was distributed to a total of 3493 participants over four years, from 2017 till 2020, to assess general knowledge about DM, including information about PA. The mean percentage of correct responses of DM general knowledge was 63.8 ± 19.0 in 2017, which decreased to 61.3 ± 18.7 in 2020 with a significant beta coefficient of −0.8 ± 0.2 (p < 0.001). Participants’ awareness about PA remained constantly high for four years: the mean percentage of correct responses was 82.1 ± 23.6 in 2017 and 82.0 ± 23.1 in 2020, and the beta coefficient was −0.5 ± 0.3 (p = 0.147). Furthermore, stratification by demographics showed that the majority of the subgroups (age, sex, educational status, marital status, having relative with DM, nationality) reported a significant declining trend in general DM knowledge. In addition, some of the subgroups also showed a declining trend in PA awareness. Future prevention efforts should assess the community’s DM knowledge regularly to tailor awareness efforts to the population segments that need heightened educational interventions.

The relation between knowledge and awareness of vitamin D (VD) and physical activity in adults has not been well studied. The present cross-sectional study aims to demonstrate this relation among adults living in Saudi Arabia. A total of 774 adults participated and were stratified based on self-reports of whether they were physically active (PA group, N = 562) or not (non-PA, N = 212). The prevalence of VD awareness and its health effects were significantly higher in the PA group compared with their counterparts (97 vs. 93.4%; p = 0.02 and 92.3 vs. 81.6%; p < 0.001, respectively). Sunlight was the preferred overall source of VD among the PA group (91.1%) followed by food, supplements, and fortified foods. Sardine, salmon, oily fish (63.7%) and eggs (54.6%) were reported as good dietary sources. Other positive attitudes, represented by taking supplement or multivitamins (51.2%), high sun exposure (33.1%), and daily duration of exposure to sunlight (15–30 min; 53.4%) were higher in the PA than the non-PA group (p values < 0.05). The body parts exposed to the sun among the PA group were arms (67.1%), hands (64.1%), face and hands (62.5%), legs (58.5%), and face (53.2%), while sunscreen cream (47.2%) was their preferred sun-protection method. High levels of knowledge and positive attitudes were reported by the PA group compared with the non-PA group in regard to walking outdoors for sun exposure (80.6 vs. 62.7%; p < 0.001). Information about good dietary sources, the role of VD in human health, associated diseases, positive attitudes to sun exposure, and the use of supplements or multivitamins were among the determinants of VD knowledge and awareness. In conclusion, VD knowledge and awareness are positively associated with self-reported physical activity in adults. Further objective classifications of PA may strengthen the results of the present investigation.

Angiogenin (ANG), a multifunctional protein known to induce blood vessel formation, is a potential biomarker for cardiovascular diseases; however, whether it is affected by vitamin D supplementation is not known. This interventional study in vitamin D-deficient Saudi adults was designed to investigate it. A total of 100 vitamin D-deficient Saudi adults aged 30–50 years were randomly selected to undergo 6-month vitamin D supplementation. Circulating levels of fasting glucose, lipids, vitamin D, apolipoproteins (AI, AII, B, CI, CII, CIII, E, and H), and ANG were measured using commercially available assays at baseline and after six months. Overall, vitamin D levels increased significantly post intervention. With this, levels of apo-CIII and apo-E significantly increased (p-values of 0.001 and 0.009, respectively) with a significant parallel decrease in apo-B (p = 0.003). ANG levels were significantly positively associated with most apolipoproteins and inversely correlated with HDL-cholesterol. Post intervention, the changes in ANG levels were positively correlated with apo-E (r = 0.32; p < 0.01 in all subjects and r = 0.40; p < 0.05 in males). Vitamin D supplementation may modestly affect ANG levels. The association observed between ANG and apo-E is worthy of further investigation since both biomarkers have been linked to neurodegenerative disorders.

Recent literature suggests that sarcopenia, often represented by low lower limbs muscle mass and strength, can be considered a potential risk factor for knee osteoarthritis (OA), but the available literature is still limited. We therefore aimed to investigate whether sarcopenia is associated with a higher risk of radiographic (ROA) and symptomatic knee OA (SxOA) in a large cohort of North American people in the context of the OA initiative. Sarcopenia at baseline was diagnosed in case of low skeletal muscle mass (i.e., lower skeletal mass index) and poor performance in the chair stands test. The outcomes of interest for this study included ROA (radiographical osteoarthritis) if a knee developed a Kellgren and Lawrence (KL) grade ≥2 at follow-up, and SxOA (symptomatic osteoarthritis) defined as new onset of a combination of painful knee OA. Altogether, 2,492 older participants (mean age: 68.4 years, 61.4% females) were included. At baseline, sarcopenia was present in 6.1% of the population. No significant difference in ROA prevalence was observed between those with and without sarcopenia (p=0.76), whilst people with sarcopenia reported a significant higher prevalence of SxOA (p

Background: Several observational studies have inconsistently demonstrated that vitamin D deficiency is a risk factor for coronavirus disease-19 (COVID-19) infection and severity. Discrepancies in results may partially be explained by the individuals’ immune profiles, which are modulated, in varying degrees, by vitamin D status and sex hormones. Methods: In this study we evaluated the differences and associations of serum levels of 25(OH)D with 34 cytokines in 220 adults (82 controls (41 males; 41 females) and 138 SARS-CoV-2 patients (79 males and 59 females)) with and without COVID-19. Results: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 group than in the controls. Serum IP-10, MCP-1, CRP, IFNγ, IL-10, IL-13, IL-17α, IL-23, and IL-6 were significantly higher in COVID-19 patients compared to controls. Serum levels of VEGF, IFNγ, IL-13, and IL-5 were significantly higher in male patients than in females. 25(OH)D was significantly correlated with EFG (R = 0.39, p < 0.05) and IL-15 (R = 0.39, p < 0.05) in male patients, while it was inversely correlated with CRP (R = −0.51, p < 0.05) in female patients. Conclusions: Altered levels of cytokines, chemokines, and vitamin D were observed in SARS-CoV-2 adult patients. These expressions were sexually dimorphic and thus highlight the sex-specific nature of the active immune response following SARS-CoV-2 infection.

Summary: Assessment and treatment pathways based on age-specific intervention thresholds in Saudi Arabi can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk. Purpose: Intervention thresholds for the treatment of osteoporosis have historically been based on the measurement of bone mineral density. The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Saudi Arabia based on fracture probabilities derived from FRAX®. Methods: The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Saudi Arabia. The methodology was applied to women age 40 years or more drawn from a tertiary referral population for skeletal assessment. Missing data for the calculation of FRAX was simulated using data from the referral and FRAX derivation cohorts. Results: Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.0% at the age of 50 years increasing to 7.6% at the age of 70 years. A total of 163 of 1365 women (11.9%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 5 women were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended for 593 women (43.4%) so that FRAX could be recalculated with the inclusion of femoral neck BMD. Of these, 220 individuals would be eligible for treatment after a BMD test and 373 women categorised at low risk after a BMD test. Conclusion: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Saudi Arabia to help guide decisions about treatment.