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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.

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

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.

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

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

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 (

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

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = −0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p &lt, 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.

Background: Epidemiological studies suggest that the Zinc-α-2-glycoprotein (ZAG) plays significant physiological roles. In this study we investigate whether ZAG could be considered as a clinical biomarker in the diagnosis and prognosis of metabolic syndrome (MetS) in Saudi population. As such insights urgently required for management of MetS. Thus, we have determined serum levels of ZAG in patients with MetS and normal individuals. We have also assessed the association between ZAG and different components of MetS. Methodology: Clinical information of 200 Saudi male and female subjects (age range 30-65) with MetS (n=100) and healthy controls (n=100) were extracted from the database of the Chair of Biomarkers of Chronic Disease (CBCD) in King Saud University (KSU), Riyadh, Saudi Arabia. MetS was screened according to NCEP ATP III criteria (National Cholesterol Education Program Adult Treatment Panel III). Fasting glucose and lipid profile levels were measured using Konelab. Serum TNF-α, IL- 6, CRP and ZAG levels were measured using commercially available assays.Results: There was age-dependent significant increase in ZAG level among MetS subjects than controls (43.8 ± 19.5 vs 48.1 ± 14.8; p = 0.04). This study demonstrates, a significant inverse association between ZAG and serum HDL-cholesterol (R= -0.20, pConclusion: High level of circulating ZAG is associated with MetS in age dependent manner. Serum ZAG might be a biomarker for MetS screening.

Tristetraprolin (TTP) is an mRNA binding protein suggested to have a substantial role in regulating the mRNA expression of numerous inflammatory factors, but data on TTP and its association with metabolic syndrome (MetS), a chronic low-grade inflammatory disorder, are scarce. We hypothesize that TTP may modulate MetS and its components. A total of 200 Saudi adults (aged 38.6 ± 8.3 years) were included in this cross-sectional study. Anthropometrics data were collected and fasting blood glucose taken for the assessment of glycemic, lipids and inflammatory markers using commercially available assays. The National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria were used to define MetS. Results showed significantly higher levels of TTP in the MetS group than in controls [288.1 pg/mL vs. 150.9 pg/mL, p &lt, 0.001]. Circulating TTP was significantly associated with tumor necrosis factor alpha [TNF-α, R = 0.30, p &lt, 0.05], interleukin 1β [IL-1β, R = 0.41, p &lt, 0.01] and C-reactive protein [CRP, R = 0.36, p &lt, 0.01], adiponectin [R = 0.36, p &lt, 0.05], insulin [R = 0.37, p &lt, 0.05], and insulin resistance [HOMA-IR, R = 0.40, p &lt, 0.05]. Receiver operating characteristics (ROC) suggest a potential use of TTP as diagnostic biomarker for MetS [AUC = 0.819, p &lt, 0.001]. The findings suggest that TTP is associated with inflammation and glycemia, which may influence MetS. TTP is a promising diagnostic biomarker for MetS which can be confirmed in larger cohorts.

Objective: Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. Study Design and Setting: A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males, 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males, 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. Results: Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values &lt, 0.05) but was not clinically significant in between-group comparisons. Kaplan–Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8, p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7, p = 0.035). Conclusion: A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.

Summary Objective The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). Methods Saudi adults with naive T2DM (n = 30; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5 × 109 cfu/g of Ecologic®Barrier (multi-strain probiotics; n = 31; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. Results Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (−3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. Conclusion Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy. Trial registration ClinicalTrials.gov Identifier: NCT01765517 .

The homeostasis of trace elements were observed to contribute to certain diabetic outcomes. This cross-sectional study determined the differences and associations between serum levels of copper (Cu), iron (Fe) and zinc (Zn) in Saudi patients with and without type 2 diabetes mellitus (T2DM) as well as those with prediabetes. Anthropometrics were measured, 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 prediabetes (aged 35–57 years). Circulating trace minerals were determined using an inductively coupled plasma–mass spectrometer. Serum levels of Cu and Fe were significantly lower in T2DM than non-T2DM (adjusted p-values &lt, 0.001). There was no difference in the Zn levels of the T2DM and non-T2DM groups. The serum Cu levels were significantly lower in the prediabetes group than the non-T2DM group (p &lt, 0.05). The serum levels of Cu, Fe and Zn were inversely associated with circulating glucose in the T2DM and prediabetes subjects (p-values &lt, 0.001). In conclusion, the differences in circulating trace elements were observed in Saudi subjects with varying glycemic statuses, suggesting an inverse association between T2DM progression and the decreasing serum Cu, Fe and Zn levels. Intervention trials are warranted to determine whether early correction of trace mineral deficiencies is beneficial in populations at higher risk for T2DM.

Studies have explored how vitamin B12 status affects sleep among elders and children, but this remains to be investigated among young adults. We used the Pittsburgh Sleep Quality Index (PSQI) to assess the association between serum vitamin B12 and sleep among female college students in Saudi Arabia. In this cross-sectional study, we enrolled 355 participants (age (years), 20.7 ± 1.5, body mass index, 23.6 kg/m2 ± 5.2) at King Saud University, Riyadh, Saudi Arabia. Fasting blood samples were analyzed regarding the serum vitamin B12 and blood lipids. Anthropometric, socio-demographic, clinical history, stress, physical activity, and dietary data were collected. We assessed the sleep statuses of the participants using the PSQI. Around 72% of the participants were “poor” sleepers (PSQI &gt, 5). Subgroup analysis within the tertiles showed that participants with higher vitamin B12 in the second and third tertiles reported better scores for sleep quality (B ± SE = −12.7 ± 5.6, p = 0.03, B ± SE = −32.7 ± 16.4, p = 0.05, respectively) and also reported a lower use of sleep medication (B ± SE = −21.2 ± 9.9, p = 0.03, in the second tertile only), after adjusting for the waist–hip ratio and stress. However, sleep was not found to be directly associated with either serum vitamin B12 or dietary vitamin B12. In conclusion, the serum vitamin B12 results show that the participants with higher vitamin B12 in the second and third tertiles reported better scores on the sleep quality scale and a lower use of sleep medication. However, no such associations were observed with the overall PSQI. More studies with larger sample sizes are needed to establish a direct relationship between sleep and vitamin B12.

Aims/Introduction This 6‐month interventional study aimed to investigate the effectiveness of different educational programs among Saudi women with prediabetes referred by primary care. Materials and Methods A total of 253 (100 group education program [GEP], 84 WhatsApp education program [WEP] and 69 control group [CG]) eligible participants were invited to take part in the study, out of whom 120 received intervention (40 GEP, 43 WEP and 37 CG). GEP participants received focused, individualized lifestyle modification advice with bimonthly support sessions, WEP participants received the same intervention, but delivered through social media (WhatsApp). The CG received standard care. Anthropometrics, biochemical profiles and macronutrient intake were measured at baseline, and 3 and 6 months. The primary end‐points were glycated hemoglobin and weight, with lipids and dietary changes as secondary outcomes. Results Glycated hemoglobin significantly improved in all groups post‐intervention (GEP baseline 6.0 ± 0.2 vs 6 months 5.5 ± 0.54; P, Education programs whether delivered through a focused educational group, social media or standard care, are equally efficacious in improving HbA1c levels among Saudi women with prediabetes. This may have been due to reduced energy intakes and favourable increases in physical activity. Digital platforms may offer a more accessible and less resource intensive option that is equally effective.

This retrospective study aimed to characterize comorbidities and associated with mortality among hospitalized adults with Covid-19 managed as perthe Saudi Ministry of Health protocol in a specialized tertiary hospital in Riyadh, Saudi Arabia. Medical records of 300 adult patients with PCR-confirmed SARS-CoV2 infection and admitted in King Salman Hospital (KSH) from May 1 to July 31, 2020 were included. Medical history, management and outcomes were noted. Males significantly outnumber females (259 versus 41). South Asians comprise 41% of all admitted patients. Mortality rate was 10% and highest among Saudi males (28.9%). Type 2 diabetes mellitus (T2DM) was the most common comorbidity (45.7%). Almost all patients (99%) had pneumonia. Patients 50 years were three times more likely to die (confidence interval, CI 1.3-6.9; p = 0.01) from Covid-19. Congestive heart failure (odds ratio OR 19.4, CI-1.5-260.0; p = 0.02) and acute kidney injury (OR 11.7, CI-4.7-28.6; p 0.001) were significantly associated with higher mortality. Dexamethasone use significantly improved the final outcome based on net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (p 0.05). In this single-center study, T2DM was very common among hospitalized Covid-19 patients. Patients 50 years, those with congestive heart failure and acute kidney injury are at higher risk for worse Covid-19 outcome.

The association between LEP G-2548A gene polymorphism with increased plasma leptin and glucose levels and blood pressure in a sample of obese Saudi patients has been evaluated. This is a cross-sectional study involved 206 Saudi adult subjects (94 males and 112 females), randomly selected from the primary health care centers, Riyadh, Saudi Arabia. The study sample was categorized into three groups: 50 normotensive ND controls (age: 47.9±5.4 yr.; BMI 22.9±2.1 Kg/m2), 80 obese normotensive ND (age: 47.7±6.0 yr.; BMI 34.1±4.2 Kg/m2) and 76 obese hypertensives with T2D patients (age: 49.4±5.9 yr.; BMI: 35.1±4.7 Kg/m2). A blood sample was collected from the participants for PCR-RFLP, chemical autoanalyzer Konelab, and Luminex instruments. Analyses of LEP G-2548A gene polymorphism were determined using polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) with 2U of HhaI restriction enzyme. Plasma leptin and insulin levels were measured using the Luminex instrument. Fasting plasma glucose, total cholesterol, HDL-cholesterol, and triglycerides were measured using a chemical autoanalyzer Konelab machine. Also, blood pressure and anthropometric data were measured. The association analysis with metabolic parameters showed that homozygous AA of the LEP gene had significantly higher plasma glucose levels and HOMA-IR compared with homozygous GG (6.8±0.55 vs. 5.8±0.30; p< 0.04; 4.1±0.84 vs. 2.6±0.67; p=0.03) respectively. Besides, heterozygous GA had significantly higher plasma leptin levels compared with homozygous GG (40.0±2.6 vs. 29.6±2.6; P= 0.04). GA, AA, GA+AA genotypes of the LEP G-2548A gene polymorphism are more prevalent among individuals with hyperglycemia (OR= 3.7, 95% CI= 1.6 to 8.4, P= 0.001; OR= 3.2, 95% CI= 1.2 to 8.6, P= 0.03; OR= 3.5, 95%CI= 1.6 to 7.7, P= 0.001) respectively. A allele of the LEP gene is more prevalent among subjects with hyperglycemia (OR= 1.9, 95%CI= 1.2 to 3.0, P=0.006). G-2548A variant of the LEP gene may not be considered as a genetic risk factor for hypertension in Saudi obese patients. However, the genotypes (GA and AA) and -2548AA allele of this gene may represent important risk factors predisposing healthy subjects to develop T2DM irrespective of the status of blood pressure.

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 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.

Objective. The role of lipid metabolism disorders in the pathogenesis of T2DM has been recognized. Lipid droplets (LDs) are dynamic organelles that store lipids. Perilipin 3 (PLIN3) is one of the five LD coat proteins that is relatively understudied as compared to other LDs. This study is aimed at determining levels of PLIN3 among adults with varying levels of obesity and insulin resistance to determine metabolic associations of PLIN3. Methodology. A total of 280 Saudi adults ( n = 127 males ; n = 153 females ) were randomly recruited and divided into three groups according to their body mass index (BMI) and fasting glucose levels: healthy and lean (HL), obese and T2DM (OD), or obese and nondiabetic (OND). Lipid profiles, fasting glucose levels, insulin, and perilipin 3 levels were measured. Results. Circulating PLIN3 was significantly lower in the OD group [8.3 ng/mL (1.2–22.5; p < 0.001 )] than the HL group [23.1 ng/mL (6.2–39.1; p < 0.001 )]. Triglycerides, total cholesterol, glucose, and insulin levels were inversely correlated with PLIN3 in all subjects. Lastly, glucose, insulin, and total cholesterol cumulatively predict circulating levels of PLIN3 by as much as 11% of the variances perceived ( p < 0.001 ). Conclusion. Circulating PLIN3 is significantly associated with insulin resistance markers and maybe a promising candidate as a protective biomarker for T2DM.

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture (R) program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

Widespread vitamin D deficiency (serum 25-hydroxyvitamin D 50 nmol/L) in Saudi Arabia (SA) has been documented, yet a time trend is needed to establish where the prevalence is headed. This study aims to fill this gap.This cross-sectional series (N = 7360) were conducted in the central region of SA from 2008 to 2017. Participants of all ages were taken from multiple cohorts that included the Biomarker Screening in Riyadh (2008-2010; N = 1460), the Osteoporosis Registry (2014-2017; N = 1225), Gestational Diabetes Mellitus cohort (2014-2017, N = 281), Vitamin D School Project (2011-2017; N = 3039) and Prediabetes cohort (2012-2017; N = 1355) master databases.Vitamin D deficiency in SA has a 10-year prevalence of 73.2 %. Between 2008-2017, the prevalence of vitamin D deficiency decreased from 87.1% to 64.7% for participants aged 18-40 years (p-trend0.001), and from 86.2% to 45.7% in participants aged40 years (p-trend0.001). During this period, vitamin D deficiency in females decreased from 80.1% to 69.6% (p-trend0.001), whereas in males, it decreased from 93.2% to 49.3% (p-trend0.001). Serum 25(OH)D was observed to have an overall increase of 2.2 ± 0.1 nmol/l (p 0.001) along with the seasonally adjusted annual increase of 1.3 ± 0.2 nmol/l from 2008 to 2017 (p 0.001).The decreasing trend in vitamin D deficiency in SA across all demographics suggests successful public health campaigns over time. It will be interesting to investigate further whether the general improvement in the vitamin D status at the community level also translated in lesser incidences of vitamin d-related diseases over time.

Background: Pro-inflammatory cytokines and adipokines upregulation through NF-κB activation in adipose tissue has been considered to have an important function in the pathogenesis of obesity-related hypertension. Objective: to ascertain the effect of NF-κB inhibitor, (SN50) on TNF-α and AGT secretion and expression in mediating the anti-inflammatory effect through its effects on NF-κB activity in human adipose tissue. Methods: Primary human adipocytes were isolated from 10 overweight and 10 obese with and without hypertension, cultured, then treated with 10 ng/ml LPS, with and without NF-κB inhibitor, SN50 (50 μg/ml) at different time points. TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cell treated and untreated with LPS and SN50 by ELISA. NF-κB p65, TNF-α and AGT proteins expression were detected by western blot. TNF-α and AGT gene expression was detected in cells and performed using quantitative RT-PCR. The study was carried out at the Obesity Research Center, King Saud University, Riyadh, KSA. Results: Treatment of AbdSc adipocytes with LPS caused a significant increase in NF-κB p65 in overweight and obese, while, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight and obese persons at all time points. Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all time points, whereas, SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours. Treatment of with LPS caused increased TNF-α and AGT gene expression, whereas, in the presence of SN50, it reduces mRNA AGT levels. Conclusion: these adipokines with NF-κB activation may represent important biomarkers to evaluate hypertension risk and provide a mechanistic insight into the pathogenesis of obesity-related hypertension.

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.

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise because of the pathogenic inflammatory nature of the abdominal fat depot. Pro-inflammatory cytokine and adipokine upregulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered to have an important function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the effect of an NF-κB inhibitor (SN50) on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its effects on NF-κB activity in human adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight subjects and 10 obese subjects with and without hypertension and treated with 10 ng/mL of lipopolysaccharides (LPS) in the presence and absence of NF-κB inhibitor SN50 (50 μg/mL). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10 ng/mL) and SN50 (50 μg/mL) using commercially available assays. The NF-κB p65 protein and AGT were detected by the western blot technique. Gene expression of TNF-α and AGT were detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of abdominal subcutaneous (AbdSc) adipocytes with LPS (10 ng/mL) caused a significant increase in NF-κB p65 in overweight subjects and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation, whereas, SN50-NF-κB inhibitor caused a reduction in NF-κB p65 in overweight subjects (p < 0.001) and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation. Treatment of AbdSc adipocytes with 10 ng/mL LPS caused a significant increase in TNF-α secretion in overweight subjects and obese subjects at all time points (p < 0.001), whereas SN50 led to a decrease in TNF-α secretion at 3 and 12 h of incubation. Treatment of AbdSc adipocytes with LPS (10 ng/mL) caused a twofold increase in TNF-α and AGT gene expression compared with untreated cells, whereas, in the presence of SN50, it reduced mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent important biomarkers to evaluate hypertension risk and may provide insight into the pathogenesis of obesity-related hypertension.

Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.\ud \ud The subjects were 64 consenting pre-menopausal women, grouped into 3: control [n = 14 lean, non-T2DM, BMI = 22.2 ± 2.2 kg/m2]; overweight [n = 16, non-T2DM, BMI = 28.5 ± 1.5 kg/m2] and T2DM [n = 34, BMI = 35.2 ± 7.7 kg/m2]. After an overnight fast, all subjects were given a standardized high-glucose (75 g) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.\ud \ud At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values

Vitamin D (VD) has been observed to have anti-inflammatory properties. However, the effects of VD supplementation on the serum amyloid P component (SAP) has not been established. This study aimed to investigate the effect of VD supplementation on serum SAP levels in Arab adults. A total of 155 VD-deficient adult Saudis (56 males and 99 females) were recruited in this non-randomized, 6-month, single-arm trial. The intervention was as follows, cholecalciferol 50,000 international units (IU) every week for the first 2 months, followed by 50,000 twice a month for the next two months, and for the last two months, 1000 IU daily. Serum 25(OH)D, SAP, C-reactive protein (CRP), lipid profile, and glucose were assessed at baseline and post-intervention. At post-intervention, VD levels were significantly increased, while SAP levels significantly decreased in all study participants. Remarkably, this reduction in SAP was more significant in males than females after stratification. SAP was inversely correlated with VD overall (r = &minus, 0.17, p &lt, 0.05), and only in males (r = &minus, 0.27, p &lt, 0.05) after stratification according to sex after 6 months of VD supplementation. Such a relationship was not observed at baseline. VD supplementation can favorably modulate serum SAP concentrations in Arab adults, particularly in males.

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18-22) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in -vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and -vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women.

Vitamin D supplementation may be used to lower oxidative stress. This interventional study aimed to investigate the effects of vitamin D supplementation on glutathione peroxidase 1 (GPx1) levels and other parameters in Arab adults with prediabetes. A total of 203 Saudi adults with prediabetes and vitamin D deficiency [intervention group, N = 146 (53 males and 93 females), control group, N = 57 (25 males and 32 females)] were included in this non-randomized, six-month intervention study. The intervention group received 50,000 international units (IU) cholecalciferol tablets once a week for two months, then twice a month for the next two months, followed by 1000 IU daily for the last two months. The control group received no supplementation. Serum 25(OH)D, lipid profile, glucose, C-reactive protein (CRP) and GPx1 were measured at baseline and after six months. Post-intervention, GPx1 concentrations increased significantly in the intervention group [17.3 (11.5&ndash, 59.0) vs 26.7 (11.4&ndash, 59.9) p &lt, 0.01] while no changes were observed in the control group (p = 0.15). This significant increase in 25(OH)D and GPx1 levels persisted after adjusting for age and BMI. Stratification according to sex revealed that this favourable increase in GPx1 was true only for males (p = 0.002). In all groups, baseline GPx1 was inversely correlated with low density lipoprotein (LDL)-cholesterol (r = &minus, 0.26, p &lt, 0.01) and body mass index (BMI) (r = &minus, 0.20, p &lt, 0.05), while positively correlated with age (r = 0.18, p &lt, 0.05) and systolic blood pressure (r = 0.19, p &lt, 0.05). In conclusion, vitamin D supplementation favourably enhanced GPx1 levels in adult Arabs with prediabetes, particularly in males.

Background: Asprosin, a novel adipokine, has been implicated in glucose regulation, insulin production, and appetite stimulation. Hence, the current study explores circulating asprosin levels and their associations with insulin resistance (IR) and other parameters in obese and type 2 diabetes mellitus (T2DM) Saudi subjects. Methods: A total of N = 291 (89 control, 105 T2DM/obese and 97 obese) subjects were included in this cross-sectional study. Fasting glucose and lipid profiles were measured routinely. Adiponectin, leptin, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1, and asprosin were measured using commercially available assays. Results: Serum asprosin levels were found to be significantly highest in obese subjects [3.7 ng/ml (2.6–5.0)] than T2DM/obese [0.1 ng/ml (0.0–0.4)] and controls [0.2 ng/ml (0.1–0.3)] (p

Introduction. Nitric oxide (NOx) is an important biomolecule which interacts with other molecules including 25(OH)D to mediate various metabolic pathways. Interactions and associations of NOx with 25(OH)D have been well studied bothin vitroandin vivo, yet associations in apparently healthy adolescents have never been studied.Methods. A total of 740 (245 boys and 495 girls) apparently healthy Saudi adolescents aged 10-17 years were included in this cross-sectional study, to determine the associations of NOx with 25(OH)D and other biomarkers in Saudi adolescents. Serum NOx, 25(OH)D, and other biochemical and anthropometric parameters were measured following standard protocols and manufacturers’ guidelines.Results. NOx level was significantly higher in boys than girls (pConclusion. The significantly inverse association of NOx and 25(OH)D among apparently healthy adolescents is influenced by sex and further strengthens the extraskeletal role of 25(OH)D in maintaining endothelial homeostasis in this age group, particularly in boys. Whether vitamin D correction can influence NOx production over time among adolescents remains to be proven.

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N = 63) and those without (N = 54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R = 0.18; p = .08) and HOMA β (R = −0.19; p = .09) as well as significant positive associations with total cholesterol (R = 0.25; p = .02), LDL-cholesterol (R = 0.25; p = .02), 25(OH)D (R = 0.22; p = .04), albumin (R = 0.30; p

The RANKL/RANK/OPG pathway regulates bone remodelling and turnover. However, the genetic background of bone mineral density (BMD) and osteopenia in Saudi postmenopausal women is yet to be studied. We studied the genetic polymorphism of RANKL/RANK/OPG with BMD and other associated factors in Saudi postmenopausal osteopenic women. A total of 439 (223 osteopenia and 216 control) postmenopausal women were recruited from the orthopaedic department of the King Khalid University Hospital, Riyadh, KSA. Genetic variants of RANK (rs1805034 and rs35211496), RANKL (rs2277438 and rs9533156), and OPG (rs2073618 and rs3102735) were genotyped using RT-PCR. Anthropometrics, bone mineral density, and other bone markers were measured. The levels of bone turnover markers, PTH, and RANKL were found to be significantly different between control and the osteopenia group. The odds ratio of 2.37 (1.00–5.69) for RANK SNP (rs1805034) indicates that subjects with CC genotype are more vulnerable to developing osteopenia as compared to subjects with TT genotype. Similarly, for RANKL SNP (rs2277438), the significant odds ratio of 20.56 (9.82–43.06) indicates that the subjects with GG genotype are at significantly higher risk of having osteopenia compared with the AA genotype subjects. In addition, G allele in rs2277438 also found to be a risk factor for osteopenia 4.54 (3.18–6.49) compared with A allele. However, none of the OPG genotypes shows association with osteopenia. The association of RANK polymorphisms with osteopenia shows its clinical importance in the diagnosis and prognosis of the bone diseases; here, we suggest that the subjects with RANK and RANKL polymorphisms may develop osteoporosis.

Summary Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods Clinical perspective and updated literature search. Results The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions.

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18–22) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in –vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and –vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women.

Gasparik, Andrea Ildiko/0000-0002-1848-2410; Gasparik, Andrea Ildiko/0000-0002-1848-2410; Cooper, Cyrus/0000-0003-3510-0709; Vrijens, Bernard/0000-0002-9090-1253; Abrahamsen, Bo/0000-0002-2730-6080; Dennison, Elaine/0000-0002-3048-4961 WOS:000501843100001 PubMed ID: 31388696 A Summary Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. Introduction Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. Methods A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. Results Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. Conclusion These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions. European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) The meeting was funded by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

The present study aimed to investigate the changes in dietary patterns of adult Saudis with prediabetes who underwent a six-month lifestyle modification program. A total of 160 Saudis with prediabetes (baseline fasting glucose 5.6&ndash, 6.9 mmol/L), aged 20&ndash, 60 years, were enrolled in one of the two arms: A one-time general advice about lifestyle modification (GA group) at orientation or a well-structured and monitored nutrition and lifestyle counseling for six months (guidance group). Fasting blood samples and a dietary recall for daily intakes of macro/micronutrients using a validated computerized food database &ldquo, ESHA&mdash, the Food Processor Nutrition Analysis program&rdquo, were collected pre- and post-intervention. Compliance to reference daily intake (RDI) was also calculated at both time points. At baseline, overall, severe deficiencies in the majority of micronutrient intakes were observed. Post intervention, clinically significant improvements in the glycemic indices (fasting glucose and insulin resistance) were seen over time in the guidance group. Also, significant improvements in dietary habits and physical activity levels were more apparent in the guidance group than the GA group, particularly in the daily intakes of total carbohydrate (46.9% compliance post vs. 20.3% at baseline), dietary fiber (21.9% vs. 3.1%), and some micronutrients like vitamin B6 (21.3% vs. 6.7%), vitamin B12 (45.3% vs. 28%), vitamin C (21.9% vs. 7.8%), riboflavin (40% vs. 10.7%), niacin (41.3% vs. 14.7%), magnesium (18.8% vs. 4.7%), iron (54.7% vs. 34.4%), and copper (37.3% vs. 13.3%). The study highlights the effects of a six-month lifestyle modification program in improving dietary micronutrient intakes of Saudis with prediabetes. Since micronutrient intake was observed to be low, fortification of these micronutrients in the Saudi diet is recommended.

Angiopoietin-like protein 8 (ANGPTL8) has a role in lipid metabolism, beta-cell proliferation and diabetes progression, however, the association between different variants in the ANGPTL8 gene and metabolic syndrome (MetS) components has not been studied widely especially in Arab ethnic groups. In this study, the associations of ANGPTL8 variants on MetS risk in Saudi Arab adults were investigated. A total of 905 unrelated Saudi adults (580 healthy controls and 325 MetS) were included. MetS was screened based on the International Diabetes Federation (IDF) criteria. The genotype and allele frequency distribution of rs737337 (T/C) and rs2278426 (C/T) polymorphism in ANGPTL8 gene was studied. Participants with MetS were significantly older, had higher BMI, and rs737337 polymorphism frequency was significantly lower than in control. Furthermore, the TC + CC genotype and C allele of rs737337 (T/C) was associated with decreased risk of hypercholesterolemia and hyperglycemia [odds ratio (OR) 0.61, 95%CI 0.40–0.93, p = 0.016 and OR 0.58, 0.39–0.86, p = 0.007 respectively for hypercholesterolemia; and OR 0.66, 0.45–0.97, p = 0.032 and OR 0.65, 0.46–0.93; p = 0.016 respectively for hyperglycemia]. Similarly, CT, CT + TT genotype and T allele of rs2278426 (C/T) were associated with decreased risk of hyperglycemia (p

There are discrepancies in the reports on the association of metabolic syndrome (MetS) and its components with bone mineral density (BMD) and hence more population-based studies on this subject are needed. In this context, this observational study was aimed to investigate the association between T-scores of BMD at lumbar L1&ndash, L4 and full MetS and its individual components. A total of 1587 participants (84.7% females), &gt, 35 years and with risk factors associated with bone loss were recruited from February 2013 to August 2016. BMD was done at L1&ndash, L4 using dual-energy X-ray absorptiometry (DXA). T-Scores were calculated. Fasting blood samples and anthropometrics were done at recruitment. Fasting lipid profile and glucose were measured. Screening for full MetS and its components was done according to the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) criteria. Logistic regression analysis revealed that the odds of having full MetS increased significantly from the lowest T-score tertile to the highest one in both sexes (OR, odd ratio (95% CI, confidence interval) of tertile 2 and 3 at 1.49 (0.8 to 2.8) and 2.46 (1.3 to 4.7), p = 0.02 in males and 1.35 (1.0 to 1.7) and 1.45 (1.1 to1.9), p &lt, 0.01 in females). The odds remained significant even after adjustments with age, body mass index (BMI), and other risk factors associated with bone loss. Among the components of MetS, only central obesity showed a significant positive association with T-score. The study suggests a significant positive association of T-score (spine) with full MetS irrespective of sex, and among the components of MetS this positive association was seen specifically with central obesity.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis, The Working Group was entirely funded by ESCEO, a Belgian not-for-profit organization. ESCEO receives unrestricted educational grants, to support its educational and scientific activities, from non-governmental organizations, not-for-profit organizations, and noncommercial and corporate partners

The study aimed to determine the influence of DBP gene polymorphisms in vitamin D metabolites before and after vitamin D supplementation. Out of 234 participants (126 females and 108 males), 146 had vitamin D deficiency (25(OH)D

The current recommended cutoff value for low vitamin D may result in overestimation of hypovitaminosis D. Vitamin D levels at 30.0 nmol/L can diagnose the hyperparathyroid cases leading to bone loss, with moderate accuracy, in the Saudi population. The new cutoff may help in identifying true cases that need clinical treatment and can reduce the burden on healthcare system. Different regions of the world have reported varying cutoff points as optimal values for vitamin D status to maintain bone health. A cross-sectional study comprising of interviews, anthropometrics, and blood samples was conducted in primary healthcare centers in Riyadh, Saudi Arabia. Standardized serum 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) were measured using electrochemiluminescence immunoassays. Independent sample and paired sample t test were conducted to compare the true means. Pearson correlation co-efficient was calculated to measure the association between original and standardized 25(OH)D. Software program, MedCalc, was utilized to measure the receiver operating curve (ROC) for determining the optimal threshold value for vitamin D. The mean standardized 25(OH)D levels for 846 males and 1285 females were (32.0 ± 14.4 nmol/L vs 31.6 ± 16.7 nmol/L) respectively. Using the gold standard PTH cutoff > 6.9 pmol/L, the ROC had an optimal criterion value for males and females at 30.0 and 24.0 nmol/L, respectively. In the males, the sensitivity and specificity were 72% and 51%, whereas in females, it was 58.2% and 66.7%, respectively. The area under the curve (AUC) was at 0.62 and 0.65 (p

Objective: Statins have several pleiotropic effects, but the literature regarding the possible relationship between use of statins and outcomes in knee osteoarthritis (OA) is limited. The aim of this study was to investigate whether statin use is associated with a lower risk of radiographic OA (ROA), radiographic symptomatic knee OA, and pain in North American individuals. Methods: A total of 4,448 community-dwelling adults from the Osteoarthritis Initiative were followed for 4 years. Statin use (including the time from baseline and the type of statin) was defined through self-report information and confirmed by a trained interviewer. Knee OA outcomes included incident ROA, symptomatic knee OA (new onset of a combination of a painful knee and ROA), and knee pain worsening (i.e., a Western Ontario and McMaster Universities Osteoarthritis Index difference between baseline and each annual examination ≥14%). Results: At baseline, 1,127 participants (25.3% of the total population) used statins. Based on a multivariable Poisson regression analysis with robust variance estimators, any use of statins was not associated with a lower risk of pain worsening (relative risk [RR] 0.97, 95% confidence interval [95% CI] 0.93–1.02), incident ROA, or symptomatic knee OA. However, statin use for more than 5 years (RR 0.91, 95% CI 0.83–0.997) and use of atorvastatin (RR 0.95, 95% CI 0.91–0.996) were associated with a reduced risk of developing pain, while rosuvastatin use was associated with a higher risk (RR 1.18, 95% CI 1.12–1.24). Analysis with adjustment for the propensity score confirmed these findings. Conclusion: The effect of statin use on knee OA outcomes remains unclear, although in our study, a significantly lower risk of developing knee pain was observed in individuals using statins for >5 years and those using atorvastatin. © 2018, American College of Rheumatology

Objectives: Mediterranean diet has several beneficial effects on health, but data regarding the association between Mediterranean diet and knee osteoarthritis (OA) are limited mainly to cross-sectional studies. We investigated whether higher Mediterranean diet adherence is prospectively associated with lower risk of radiographic OA (ROA), radiographic symptomatic knee OA (SxOA) and pain worsening in North American people at high risk or having knee OA. Methods: Adherence to the Mediterranean diet was evaluated using a validated Mediterranean diet score (aMED), categorized in five categories (Q1 to Q5, higher values reflecting higher adherence to Mediterranean diet). Knee OA outcomes included incident (1) ROA, (2) SxOA, as the new onset of a combination of a painful knee and ROA, (3) knee pain worsening, i.e. a Western Ontario and McMaster Universities Osteoarthritis Index difference between baseline and each annual exam of ≥14%. Results: 4330 subjects (mean age: 61.1 years; 58.0% females) were included. Based on a multivariable Poisson regression analysis, during a mean follow-up period of 4 years, participants who were more highly adherent to a Mediterranean diet (Q5) reported lower risk of pain worsening (relative risk, RR = 0.96; 95% CI: 0.91–0.999) compared to those in Q1. In 2994 people free from SxOA at baseline, higher adherence to a Mediterranean diet was associated with a lower risk for SxOA during follow-up by 9% (Q5 vs. Q1; RR = 0.91; 95% CI: 0.82–0.998). No significant associations emerged between aMED and incident ROA. Conclusion: Higher adherence to Mediterranean diet is associated with a lower risk of pain worsening and symptomatic forms of knee OA. © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

The study examined the associations between physical activity and appendicular lean mass (ALM), fat mass, and bone mineral density (BMD) and examined the role of physical activity on these variables. The participants included 497 men (age: 32.2±10.4 years and body mass index: 28.2±5.4 kg/m2). The study was cross-sectional, and measurements included body composition measured on dual-energy X-ray absorptiometry and self-reported physical activity assessed using the International Physical Activity Questionnaire. Physical activity, including light physical activity, was associated with increased ALM (P≤0.05). Fat indicators, including waist circumference, were positively associated with ALM (P≤0.05), but not with BMD. Physical activity, including moderate-to-vigorous physical activity, was not associated with BMD, whereas ALM and handgrip strength were significantly associated with BMD (P≤0.05). Physical activity independent of exercise intensity was directly associated with ALM and indirectly associated with BMD through increased muscle mass and strength.

Objectives: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. Methods: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. Results: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. Conclusions: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues., The meeting was funded by the ESCEO, a Belgian not-for-profit organization. The authors thank the Chair for Biomarkers of Chronic Diseases and the International Scientific Partnership Program (ISPP#0111) at King Saud University, Riyadh, Saudi Arabia for their support