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

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

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

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

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

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

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

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

SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects.

BACKGROUND: Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population. METHODS: Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected. RESULTS: Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016). CONCLUSIONS: SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin.

Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2.

BACKGROUND: Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in 'browning' of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2. MATERIAL AND METHODS: In this cross-sectional study, 164 Saudi adults: 81 non-DMT2 controls [age: (mean ± SD) 51.6 ± 10.9; BMI: 29.6 ± 4.3 kg/m(2) ] and 83 DMT2 subjects [age: 54.3 ± 10.3 year; BMI: 29.4 ± 4.7 kg/m(2) ] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme-linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity. RESULTS: We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0.001). FIT index was positively associated (r = 0.20, P = 0.03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0.75 ± 0.07 µg/mL) than tertile 1 (0.49 ± 0.06 µg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects. CONCLUSION: This cross-sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.

Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects.

BACKGROUND: Irisin, a novel myokine, increases energy expenditure and glucose tolerance and, thus, improves carbohydrate homeostasis in humans. This hormone has potential therapeutic applications for weight loss and improvement in insulin resistance in subjects with obesity and diabetes mellitus type 2 (T2DM). In this cross-sectional study, we aimed to associate circulating levels of irisin and several anthropometric and metabolic parameters among Arab children. METHODS: A cohort of 153 Saudi children, 81 boys [age: 12·4 ± 3·2 years; BMI: 19·5 ± 5·9 kg/m(2) ] and 72 girls: [age: 12·9 ± 3·2 years; BMI: 20·6 ± 5·2], were examined. Anthropometry was obtained, and fasted bloods were collected for biochemical analyses. Irisin was assessed by a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Girls had higher circulating irisin levels than boys (P = 0·04). There were several significant correlations between circulating irisin and fasting blood glucose (FBG) (r = -0·35, P < 0·001), sagittal abdominal diameter (SAD) (r = -0·34, P < 0·001) and HDL cholesterol (r = 0·17, P = 0·04) across the entire cohort studied. Notably in girls, but not in boys, HOMA-IR correlated negatively with irisin levels (r = -0·32, P = 0·02), as previously noted in adults. FBG was a significant predictor of circulating irisin (R(2)  = 0·16) followed by SAD. In multivariate linear regression analysis, after controlling for potential confounders such as gender, age and BMI, irisin levels were independently associated with FBG (ß = -0·34, P = 0·01), particularly in girls. CONCLUSION: Serum irisin levels were higher in girls than in boys and correlated negatively with HOMA-IR. They were also independently associated with FBG predominantly in girls, suggesting that this hormone may play a crucial role in glucose metabolism from an early age.

Maternal inheritance of circulating irisin in humans.

The recently discovered myokine irisin has been implicated in several observational studies as a potential therapeutic target for obesity-related diseases. However, no information is available as to the heritability of this hormone. The present study aims to fill this gap. A total of 120 families (n=254; 121 adults and 133 children) were included in the study taken from the Riyadh Biomarkers Research Program cohort. Information gathered include anthropometrics, and glycaemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Examining heritability between mother and offspring, the most significant heritable traits in sons included irisin (P=1.6×10(-5)), systolic blood pressure (P=3.6×10(-4)), total cholesterol (P=3.5×10(-7)) and LDL (low-density lipoprotein)-cholesterol (P=1.2×10(-6)). Heritable traits between mother and daughter again included irisin (P<0.002), as well as anthropometric associations such as waist (P<0.01) and hip (P<0.005) circumference and blood pressure (P<0.002); biochemically, principal associations were observed with HDL (high-density lipoprotein)-cholesterol (P<0.04) and TNF-α (tumour necrosis factor-α) (P<0.002). HDL-cholesterol was the single most significant predictor for irisin levels in adults, explaining 17% of the variance, whereas in children AngII (angiotensin II) was the most significant predictor of irisin levels, explaining 19% of the variance (P=0.003). Circulating irisin appears to be maternally inherited and is predicted by HDL-cholesterol in adults and AngII in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy-generating processes.

Does visceral adiposity index signify early metabolic risk in children and adolescents?: association with insulin resistance, adipokines, and subclinical inflammation.

BACKGROUND: Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap. METHODS: In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained. RESULTS: A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m(2)). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment-insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose. CONCLUSION: Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

Circulating Nitric Oxide and Metabolic Syndrome in Arab Children and Adolescents: A Case-Control Study.

BACKGROUND: Metabolic syndrome (MetS) represents a cluster of known cardiometabolic risk factors, which elevates the risk of type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) in adults and, only recently, even in children and adolescents. Circulating nitric oxide (NOx) has been observed to influence MetS risk factors in adults, but this has been scarcely investigated in children. The aim of the present study was to determine whether circulating NOx levels correlate with known components of MetS in Arab children and adolescents. METHODS: Anthropometrics, serum NOx, lipid profile and fasting glucose levels were measured in 740 Saudi Arabs aged 10-17 years (68.8% girls). The presence of MetS was screened using the criteria of de Ferranti et al. Results: Overall, serum NOx levels were significantly higher in MetS participants compared to non-MetS (25.7 µmol/L (10.1-46.7) versus 11.9 µmol/L (5.5-22.9), p < 0.001) even after adjustments for age, BMI and sex. With the exception of elevated blood pressure, higher circulating NOx significantly increased the odds for MetS and its components. Lastly, receiver operating characteristics (ROC) showed that NOx, as a diagnostic marker for MetS, had good sensitivity and was higher in boys than girls (all MetS participants: area under the curve (AUC) = 0.68, p < 0.001), (girls with MetS: AUC = 0.62, p = 0.002), (boys with MetS: AUC = 0.83, p < 0.001)). CONCLUSIONS: MetS and most of its components were significantly associated with circulating NOx levels in Arab adolescents and may be a promising diagnostic biomarker for MetS.

Attendance-Based Adherence and Outcomes of Obesity Management Program in Arab Adolescents.

Pediatric obesity has become a global pandemic in the last century, contributing to short and long-term medical conditions that heighten the risk of morbidity and mortality in children. The 12-month school-based obesity management educational program aims to assess the effect of adherence to the lifestyle educational program and target outcomes, obesity, and hypertension. A total of 363 (nonadherent, N = 179; adherent, N = 184) Saudi school adolescents aged 12-18 were recruited from 60 schools in Riyadh City, Saudi Arabia. Anthropometrics, lipid profile, and blood glucose were measured at baseline and post-intervention. The level of adherence was based on the number of attended educational sessions, and participants were grouped accordingly into two groups: adherent group (attended ≥ 3 sessions) and nonadherent group (attended 1-2 sessions) out of a total of five sessions. Results demonstrated that significantly more participants in the adherent group achieved the primary program goal of reducing obesity indices [body weight, body mass index (BMI), and BMI z-score] than the nonadherent group. Additionally, among adherent obese participants, BMI z-score significantly decreased after the 12-month intervention (post-intervention: 1.5 ± 0.7 vs. baseline: 1.7 ± 0.6, p < 0.05), while the trend in BMI z-score modestly increased in the nonadherent obese participants post-intervention (post-intervention: 1.8 ± 0.7 vs. baseline: 1.7 ± 0.6, p > 0.05). Moreover, there was a substantial reduction in hypertension prevalence only in the adherent group (p = 0.003) and among adherent obese participants in particular (p = 0.03). Furthermore, adherence to session attendance was higher in girls than boys, which led to better outcomes among girls than boys. For the secondary outcomes, lipid profile indices increased in both groups, while no changes were observed in the glycemic profile. In conclusion, greater adherence to educational sessions achieved modest but favorable weight changes and improved blood pressure among obese adolescents. Future intervention studies should take into consideration the need to improve attendance to enhance adherence to the program among adolescents at risk.

Regional Variations in Pesticide Residue Detection Rates and Concentrations in Saudi Arabian Crops.

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.

Differences and Associations of NLRP3 Inflammasome Levels with Interleukins 1α, 1ß, 33 and 37 in Adults with Prediabetes and Type 2 Diabetes Mellitus.

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

Fenugreek extract as an inducer of cellular death via autophagy in human T lymphoma Jurkat cells.

BACKGROUND: Drugs used both in classical chemotherapy and the more recent targeted therapy do not have cancer cell specificity and, hence, cause severe systemic side effects. Tumors also develop resistance to such drugs due to heterogeneity of cell types and clonal selection. Several traditional dietary ingredients from plants, on the other hand, have been shown to act on multiple targets/pathways, and may overcome drug resistance. The dietary agents are safe and readily available. However, application of plant components for cancer treatment/prevention requires better understanding of anticancer functions and elucidation of their mechanisms of action. The current study focuses on the anticancer properties of fenugreek, a herb with proven anti-diabetic, antitumor and immune-stimulating functions. METHOD: Jurkat cells were incubated with 30 to 1500 µg/mL concentrations of 50% ethanolic extract of dry fenugreek seeds and were followed for changes in viability (trypan blue assay), morphology (microscopic examination) and autophagic marker LC3 transcript level (RT-PCR). RESULTS: Incubation of Jurkat cells with fenugreek extract at concentrations ranging from 30 to 1500 µg/mL for up to 3 days resulted in cell death in a dose- and time-dependent manner. Jurkat cell death was preceded by the appearance of multiple large vacuoles, which coincided with transcriptional up-regulation of LC3. GC-MS analysis of fenugreek extract indicated the presence of several compounds with anticancer properties, including gingerol (4.82%), cedrene (2.91%), zingerone (16.5%), vanillin (1.52%) and eugenol (1.25%). CONCLUSIONS: Distinct morphological changes involving appearance of large vacuoles, membrane disintegration and increased expression of LC3 transcripts indicated that fenugreek extract induced autophagy and autophagy-associated death of Jurkat cells. In addition to the already known apoptotic activation, induction of autophagy may be an additional mechanism underlying the anticancer properties of fenugreek. This is the first report showing fenugreek as an inducer of autophagy in human cells and further work is needed to define the various intermediates of the autophagic pathway.

Effects of a 12-Month Hybrid (In-Person + Virtual) Education Program in the Glycemic Status of Arab Youth.

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

Cardiometabolic Effects of a 12-Month, COVID-19 Lockdown-Interrupted Lifestyle Education Program for Arab Adolescents.

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

Evaluation of 34 Cytokines and Vitamin D Status Reveal A Sexually-Dimorphic Active Immune Response to SARS-CoV-2.

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

Increasing Prevalence of Pediatric Metabolic Syndrome and Its Components among Arab Youth: A Time-Series Study from 2010-2019.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of cardiometabolic disorders, mostly studied in adults with certain ethnic groups, such as Arabs with higher predisposition and heritability. In this time-series study, we tried to determine the prevalence of MetS in the Arabic pediatric population from 2010-2019 to gauge the need to intervene in the younger population. METHODS: A total of 7985 Saudi school children aged 12-18 coming from different sets of cohorts in different timepoints were included in this time-series studies (Year 2010, n = 2081, 877 boys and 1204 girls; Year 2015, n = 3360, 1625 boys and 1735 girls, Year 2019, n = 2544, 956 boys and 1588 girls). Anthropometrics were measured as well as fasting blood samples for the assessment of lipids and glucose. Screening for MetS was conducted using the pediatric definition obtained from the 2004 definition of de Ferranti et al. Results: In 2010, the prevalence of MetS was 11.8%, which increased sharply to 20.1% in 2015 and again in 2019 to 20.6%. Stratified according to sex, the increased prevalence of MetS was more evident in boys with only 7.8% in 2010 jumping to 25.3% in 2019. In girls, the increase in prevalence was modest with 14.8% in 2010 to 17.7% in 2019. In both boys and girls, the highest increase in prevalence among MetS components was observed to be low HDL-cholesterol, elevated triglycerides, and central obesity, respectively. CONCLUSIONS: The alarming increase in pediatric MetS among Arab children and adolescents over a short timespan have significant clinical and economic implications if not addressed immediately. Health policy makers should implement lifestyle interventions aimed at high-risk children or overweight youths.

Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.

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 < 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.

Tristetraprolin, Inflammation, and Metabolic Syndrome in Arab Adults: A Case Control Study.

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 < 0.001]. Circulating TTP was significantly associated with tumor necrosis factor alpha [TNF-α, R = 0.30, p < 0.05], interleukin 1ß [IL-1ß, R = 0.41, p < 0.01] and C-reactive protein [CRP, R = 0.36, p < 0.01], adiponectin [R = 0.36, p < 0.05], insulin [R = 0.37, p < 0.05], and insulin resistance [HOMA-IR, R = 0.40, p < 0.05]. Receiver operating characteristics (ROC) suggest a potential use of TTP as diagnostic biomarker for MetS [AUC = 0.819, p < 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.