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Osteoporosis in men remains a significantly underrecognized condition, with notable differences in bone mineral density (BMD) and fracture risk between Asian and Western populations. Despite 30% of hip fractures globally occurring in men, they are less likely to be diagnosed or treated for osteoporosis, especially in resource-limited settings. Given these disparities, a deeper understanding of osteoporosis epidemiology and treatment efficacy in men is essential, particularly in Asian populations.This review synthesizes the latest evidence on the epidemiology, screening, and treatment of osteoporosis in men, with a focus on genetic, environmental, and epidemiological disparities between Eastern and Western populations. Additionally, the review examines existing controversies surrounding fracture risk screening in men and evaluates the efficacy and cost-effectiveness of pharmacological treatments such as bisphosphonates, denosumab, and anabolic agents.Asian men exhibit lower peak BMD compared to their Caucasian counterparts, leading to potential misdiagnoses when using Caucasian-based BMD reference ranges. Screening tools like the Fracture Risk Assessment Tool (FRAX)® show variability in performance across populations. Data on pharmacological treatment in men remain limited, although studies suggest comparable benefits to those observed in women. Larger studies, particularly in male and Asian populations, are urgently needed to refine diagnostic and therapeutic guidelines.Osteoporosis in men is underdiagnosed and undertreated globally, with pronounced disparities between populations. Current diagnostic tools and treatment protocols are not fully tailored to male and Asian populations. There is an urgent need for longitudinal studies focusing on male-specific osteoporosis management to reduce fracture risk and improve outcomes.

Aim: This study evaluated the pesticide residues in some fruits collected from different markets in Saudi Arabia (SA) and determined potential health risks associated with them. Methods: Concentrations of pesticide residues in 12 types of fruits from local markets in SA from 2020 to 2022 were collected and evaluated. Multiple residue extraction method QuEChERS followed by LC-MS/MS and GC–MS/MS, were used to analyze 161 samples. Results: Only 10 out of 161 samples (6.2 %) were free of pesticides. A total of 132 (87.4 %) pesticide residues were below MRLs, with 19 (12 %) of samples exceeding MRLs. Detected pesticide residues belonged to different chemical classes of pesticides including organophosphates, pyrethroids, organochlorines, neonicotinoids and fungicides. Risk assessment of human exposure to pesticides via the intake of the fruit types was performed. Hazard index (HI) for most fruit types were found to be less than 1. Oranges, grapes and pomegranates were the most consumed fruit types (31.6 g/day,15.8 g/day,10.8 g/day) and were contaminated with pesticide residues. Fluopyram, imazalil, chlorpyrifos, finamiphos and indoxacarb had HIs (1.32, 2.76,3.6,3.6,1.5) showed high risk index suggesting risk for systemic toxicity in consumers dependent on the amount of consumption. Conclusion: In summary, high detection rate of pesticide residues was found in different fruits sold in local markets in SA. Regular biomonitoring programs for food crops in SA markets should be enforced, particularly in identified crops with His >1 to increase food safety within the SA community.

Pesticide residues and persistent organic pollutants (POPs) are known hazardous chemicals that exhibits bioaccumulation in organisms and the ecosystem in general. There is limited evidence on the levels of these contaminants among common Saudi crops grown as well as the effects of season on their levels. Hence, the present investigated the levels of pesticide residues in major fruit and vegetable crops collected during the winter and summer seasons in Saudi Arabia (SA). A total of 392 samples taken from 28 locally produced vegetables and fruits were purchased from local markets in Riyadh, SA during peak summer (N = 263) (June-August 2022) and peak winter (N = 129) (December-February 2022). Food samples were extracted and cleaned up using the modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) technique. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC–MS/MS) instruments were used to determine pesticide residues. Crops that had the highest percentage exceeding the maximum residue limit (MRL) include pepper (7.9 %) as well as apricot, fig and pomegranates (3.1 %). Cypermethrin was the most prevalent pesticide residue in both winter and summer samples with detection rates of 13.2 % and 14.1 % respectively (p = 0.33). Thiamethoxam detection rates was significantly higher in winter (7.8 %) than summer (3.0 %) (p = 0.04). There is a high detection rate of pesticide residues in SA independent of season, with cypermethrin being the most common. Thiamethoxam is more commonly detected in winter than summer crops. The study should be extended to include other potential sources of pesticide residues such as fishes grown in aqua farms and other poultry products.

Abstract 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 correlation between ZAG and different components of MetS. In this case–control study, 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. There was an age-dependent significant increase in ZAG level among MetS subjects than controls (43.8 ± 19.5 vs 48.1 ± 14.8; P = 0.04). A significant inverse correlation between ZAG and serum HDL-cholesterol (r = − 0.20, P

Protein misfolding can result in amyloid fiber aggregation, which is associated with various types of diseases. Therefore, preventing or treating abnormally folded proteins may provide therapeutic intervention for these diseases. Valsartan (VAL) is an angiotensin II receptor blocker (ARB) that is used to treat hypertension. In this study, we examine the anti-aggregating effect of VAL against hen egg-white lysozyme (HEWL) amyloid fibrils through spectroscopy, docking, and microscopic analysis. In vitro formation of HEWL amyloid fibrils was indicated by increased turbidity, RLS (Rayleigh light scattering), and ThT fluorescence intensity. 10 μM VAL, amyloid/aggregation was inhibited up to 83% and 72% as measured by ThT and RLS respectively. In contrast, 100 μM VAL significantly increases the fibril aggregation of HEWL. CD spectroscopy results show a stabilization of HEWL α-helical structures in the presence of 10 μM VAL while the increase in β-sheet was detected at 100 μM concentration of VAL. The hydrophobicity of HEWL was increased at 100 μM VAL, suggesting the promotion of aggregation via its self-association. Steady-state quenching revealed that VAL and HEWL interact spontaneously via hydrogen bonds and van der Waals forces. Transmission electron microscopy (TEM) images illustrate that the needle-like fibers of HEWL amyloid were reduced at 10 μM VAL, while at 100 μM the fibrils of amyloid were increased. Additionally, our computational studies showed that VAL could bind to two binding sites within HEWL. In the BS-1 domain of HEWL, VAL binds to ASN59, ILE98, ILE58, TRP108, VAL109, SER50, ASP52, ASN59, ALA107, and TRP108 residues with a binding energy of −9.72 kcal mol−1. Also, it binds to GLU7, ALA10, ALA11, CYS6, ARG128, and ARG14 in the BS-2 domain with a binding energy of −5.89 kcal mol−1. VAL, therefore, appears to have dual effect against HEWL aggregation. We suggest that VAL stabilizes HEWL's aggregation-prone region (APR) at 10 μM, preventing aggregation. Also, we assume that at 100 μM, VAL occupies BS-2 beside BS-1 and destabilizes the folding structure of HEWL, resulting in aggregation. Further studies are needed to investigate the mechanism of action and determine its potential side effects.

There is a scarcity of evidence on the levels of pesticide residues among common crops grown in the different regions of the Kingdom of Saudi Arabia (KSA). The present study aims to fill this gap. We collected samples across four regions of KSA (N = 41 from the west, N = 146 from the central, N = 131 from the north and N = 74 samples from the east). Food samples were extracted and cleaned using the modified quick, easy, cheap, effective, rugged and safe (QuEChERS) methodology. Tandem mass (LC-MS/MS and GC-MS/MS) was used to detect pesticide residues. The highest pesticide residue detection rate was 89.7% in the central region, followed by 88.5% in the north, 83.8% in the east and 70.7% in the western region (p = 0.01). Pesticide residue detection rates were significantly higher in fruits than vegetables (p = 0.02). Cypermethrin detection was most common overall, particularly in the Western region (p = 0.002), and pyraclostrobin concentration was the highest among all residues investigated. In conclusion, high detection rates of moderately hazardous pesticide residues were found in various crops across regions in KSA. Routine biomonitoring programs across KSA regions should be implemented, as well as public health campaigns to decrease pesticide residue consumption and exposure.

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 (

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.

The present study aimed to determine the serum organochlorine pesticides (OCPs) levels and risk of exposure among Saudi adults. Most OCPs are considered as endocrine-disrupting chemicals, and exposure can induce adverse health effects in both humans and wildlife. Serum OCP levels have not been documented in the Saudi population. Serum OCP concentrations were quantified using gas chromatography mass spectrometry (GC-MS/MS) in 302 serum samples collected from adult Saudis. All studied OCPs were detected in all participants. High concentrations of DDT and its metabolites (DDE and DDD) were detected in both males and females, with concentrations being significantly higher in males. High concentrations of 2,4-DDE, 4,4-DDE, and gamma-HCH were detected (18.31, 16.12, and 15.15 ng g−1 lipid and 5.9, 7.1, and 8.6 ng g−1 lipid for males and females, respectively). Alpha-HCH, Beta-HCH, 2,4-DDT, and 4,4-DDT were detected at concentrations lower than 2 ng g−1. Levels of OCPs varied according to age and body mass index (BMI). Serum concentrations of OCPs significantly differed between Saudi males and females and were influenced by age and BMI. This study is the first to document serum OCP concentrations in Saudi adults from Riyadh, KSA. Monitoring programs are suggested for evaluating serum OCP concentrations in the general population to track toxicity levels and serve as an indicator of possible adverse health effects. Keywords: Organochlorine pesticides, GC-MS/MS, Public health, Saudi Arabia

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.

Alpha-amylase (α-amylase) is a key player in the management of diabetes and its related complications. This study was intended to have an insight into the binding of caffeic acid and coumaric acid with α-amylase and analyze the effect of these compounds on the formation of advanced glycation end-products (AGEs). Fluorescence quenching studies suggested that both the compounds showed an appreciable binding affinity towards α-amylase. The evaluation of thermodynamic parameters (ΔH and ΔS) suggested that the α-amylase-caffeic/coumaric acid complex formation is driven by van der Waals force and hydrogen bonding, and thus complexation process is seemingly specific. Moreover, glycation and oxidation studies were also performed to explore the multitarget to manage diabetes complications. Caffeic and coumaric acid both inhibited fructosamine content and AGE fluorescence, suggesting their role in the inhibition of early and advanced glycation end-products (AGEs). However, the glycation inhibitory potential of caffeic acid was more in comparison to p-coumaric acid. This high antiglycative potential can be attributed to its additional –OH group and high antioxidant activity. There was a significant recovery of 84.5% in free thiol groups in the presence of caffeic acid, while coumaric attenuated the slow recovery of 29.4% of thiol groups. In vitro studies were further entrenched by in silico studies. Molecular docking studies revealed that caffeic acid formed six hydrogen bonds (Trp 59, Gln 63, Arg 195, Arg 195, Asp 197 and Asp 197) while coumaric acid formed four H-bonds with Trp 59, Gln 63, Arg 195 and Asp 300. Our studies highlighted the role of hydrogen bonding, and the ligands such as caffeic or coumaric acid could be exploited to design antidiabetic drugs.

Introduction: This study aimed to investigate the association between components of metabolic syndrome (MetS) at first trimester and development of Gestational diabetes mellitus (GDM) in 498 Saudi pregnant women.Materials and Methods: Biochemical and anthropometric parameters were determined at the first trimester and MetS components were defined. Participants were screened for GDM at follow up according to International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. The main outcome measures were development of GDM and GDM risk vs. MetS components at first trimester.Results: One hundred twenty three (24.7%) were diagnosed with GDM according to IADPSG criteria. GDM risk was significantly higher for participants with hypertriglyceridemia at 1st trimester even after adjusting for age, BMI and parity (OR: 1.82; CI: 1.1–3.7, p = 0.04). Furthermore, the odds of hyperglycemia at 1st trimester was significantly higher in GDM than in non-GDM participants even after adjustments (OR: 2.13, 95% CI: 1.1 to 4.3, p = 0.038). The receiver operating characteristic (ROC) for predicting GDM revealed an area under the curve (AUC) of 0.69 (95% CI: 0.64 to 0.74, p < 0.001) and 0.71 (95% CI: 0.65 to 0.77, p < 0.001) for first-trimester hyperglycemia and hypertriglyceridemia respectively.Conclusions: The incidence of GDM in Saudi pregnant women was strongly associated with hyperglycemia and hypertriglyceridemia at first trimester. These findings are of clinical importance, as an assessment of MetS in early pregnancy can identify women at higher risk of developing GDM.

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.

Abstract Background The present randomized clinical trial characterized the beneficial effects of a multi-strain probiotics supplementation on improving circulating endotoxin levels (primary endpoint) and other cardiometabolic biomarkers (secondary endpoint) in patients with T2DM. Methods A total of 78 adult Saudi T2DM patients (naïve and without co-morbidities) participated in this clinical trial and were randomized to receive twice daily placebo or probiotics [(2.5 × 109 cfu/g) containing the following bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58 (Ecologic®Barrier)] in a double-blind manner for 12 weeks. Anthropometrics and cardiometabolic profiles were obtained at baseline and after 12/13 weeks of treatment. Results After 12/13 weeks of intervention and using intention-to-treat analysis, no difference was noted in endotoxin levels between groups [Placebo − 9.5% vs. Probiotics − 52.2%; (CI − 0.05 to 0.36; p = 0.15)]. Compared with the placebo group however, participants in the probiotics groups had a significant but modest improvement in WHR [Placebo 0.0% vs. Probiotics 1.11%; (CI − 0.12 to − 0.01; p = 0.02)] as well as a clinically significant improvement in HOMA-IR [Placebo − 12.2% vs. Probiotics − 60.4%; (CI − 0.34 to − 0.01; p = 0.04)]. Conclusion Using a multi-strain probiotic supplement daily for 12/13 weeks significantly improved HOMA-IR and modestly reduced abdominal adiposity among medication naïve T2DM patients. Trial Registration: ClinicalTrials.gov Identifier: NCT01765517 , Registered January 10, 2013

Abstract Background Altered expression of receptor tyrosine kinases (RTKs) is a major driver of growth and metastasis of cancers. Recepteur d’origine nantais (RON) receptor is a single-pass transmembrane RTK aberrantly expressed in a number of cancers. Efforts to block deregulated RON signaling in tumors using small molecule kinase inhibitors or antibodies are complicated by the presence of unknown number/types of isoforms of RON, which, despite having similar sequences, are localized differently and mediate varied functions. The objective of this study was to identify splice variants of RON transcripts between exons 1 and 10 that code for the extracellular region. Methods Direct cDNA sequencing was performed for the transcript between exons 1–10 of RON by Sanger sequencing in various lung cancer cell lines. Results PCR amplification and bi-directional sequencing of cDNA for section between exons 1 and 10 from lung cancer cell lines revealed the presence of several splice variants of RON transcripts; the variants were formed by skipping of exons 2, 2–3, 5–6, 6 and 8–9. Each of these transcript variants were found in one or more cell lines. While the variants formed by skipping of exons 2, 2–3 and 5–6 resulted in loss of 63, 106 and 109 amino acids, respectively, and didn’t cause reading-frameshift, the transcripts formed by skipping of exons 6 and 8–9 caused reading-frameshift. Splice variant lacking exons 8–9 was found in 13 out of 23 cell lines tested. Conclusion Lung cancer cell lines contain several splice variants of RON which involve skipping of exons coding for extracellular region. Some of the splicing changes result in reading-frameshift and the N-terminally truncated isoforms are expected to be secreted out. The ubiquitous nature of alternative splicing events in RON suggests the need for isoform specific approaches to functional analysis and therapeutic targeting of RON.

Abstract There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p

The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150–250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

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 (11.5−59.0) vs 26.7 (11.4−59.9) p < 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 = −0.26, p < 0.01) and body mass index (BMI) (r = −0.20, p < 0.05), while positively correlated with age (r = 0.18, p < 0.05) and systolic blood pressure (r = 0.19, p < 0.05). In conclusion, vitamin D supplementation favourably enhanced GPx1 levels in adult Arabs with prediabetes, particularly in males.

A possible role of Snap25 polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 in Snap25 using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f=4.41, df=1, and p=0.03 and f=5.31, df=1, and p=0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f=7.29, df=1, and p=0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p=0.01 and OR: 1.05), HbA1c levels (OR: 5.06 and p=0.02), and lower insulinemia (p=0.03 and OR: 0.95) in T2DM patients. The minor Snap25 rs363050 (G) allele, which results in a reduced expression of Snap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin.

To explore the mechanisms underlying the suggested role of the vitamin D/vitamin D receptor (VDR) complex in the pathogenesis of obesity we performed genetic and immunologic analyses in obese and non-obese Saudi individuals without other concomitant chronic diseases. Genomic DNA was genotyped for gene single nucleotide polymorphisms (SNPs) of VDR by allelic discrimination in 402 obese (body mass index -BMI≥30 kg/m2) and 489 non-obese (BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m(2)), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m(2)), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m(2)) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m(2)). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p

Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFα), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFα, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ∼50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.

A decade has passed since metabolic syndrome (MetS) was documented to be highly prevalent in the kingdom of Saudi Arabia. No follow-up epidemiologic study was done. This study aims to fill this gap. In this cross-sectional, observational study, a total of 2850 randomly selected Saudi adults aged 18-55 years were recruited. Subjects' information was generated from a database of more than 10,000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort), Saudi Arabia. Anthropometrics included body mass index (BMI), blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The definition of ATP-III (NHANES III) was used for the diagnosis of the full MetS. The overall prevalence of complete MetS was 35.3% [Confidence-Interval (CI) 33.5-37.01]. Age-adjusted prevalence according to the European standard population is 37.0%. Low HDL-cholesterol was the most prevalent of all MetS risk factors, affecting 88.6% (CI 87.5-89.7) and hypertriglyceridemia the second most prevalent, affecting 34% (CI 32.3-35.7) of the subjects. The prevalence of the full MetS decreased from previous estimates but remains high, while dyslipidemia remains extremely high, affecting almost 90% of middle-aged Arabs. Screening for dyslipidemia among Saudi adults is warranted, especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of etiologic therapies.