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

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

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

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

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

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

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

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

The study aimed to explore the influence of the COVID-19 lockdown on the mental status and dietary intake of residents in Saudi Arabia. In this cross-sectional study, an online survey was conducted from 11 May to 6 June 2020 corresponding to almost two weeks during and after Ramadan (23 April–23 May 2020). The Patient Health Questionnaire was used to assess anxiety, depression, and insomnia. Logistic regression analysis was used to identify predictors of anxiety, depression, and insomnia. The prevalence of anxiety, depression, and insomnia among the participants was 25.4%, 27.7%, and 19.6%, respectively. Participants aged ≥50 years with high income (≥8000 SAR) were at a lower risk of developing depression, whereas participants of the same age group with income 5000–7000 SAR were at high risk of developing anxiety. Students and master-educated participants suffer from median elevated depression and are required to take more multivitamins and vitamin D than others. Anxiety and depression were more common among married participants with low income. There is a wide range of Saudi residents who are at a higher risk of mental illness during the COVID-19 pandemic. Policymakers and mental healthcare providers are advised to provide continuous monitoring of the psychological consequences during this pandemic and provide mental support.

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19&ndash, 30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of &lt, 148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = &minus, 0.26, p &lt, 0.001), low-density lipoprotein cholesterol levels (B = &minus, 0.30, 0.001), and triglyceride (B = &minus, 0.16, 0.01) after adjusting for potential confounders, while obesity indices of body mass index, central obesity, and fat percentage showed no association. Therefore, we conclude that low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women. Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles.

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.

This three-arm, randomized, controlled study aimed to determine the differences in the effects of general advice (GA) on lifestyle change, intensive lifestyle modification programme (ILMP) and GA + metformin (GA + Met) in reducing the prevalence of full metabolic syndrome (MetS) in subjects with prediabetes; 294 Saudis with prediabetes (fasting glucose 5.6–6.9 mmol/L) were initially randomized, 263 completed 6 months and 237 completed 12 months. They were allocated into three groups: GA group which received a standard lifestyle change education; ILMP which followed a rigorous lifestyle modification support on diet and physical activity; and a GA + Met group. Anthropometric and biochemical estimations were measured. Full MetS (primary endpoint) and its components (secondary endpoint) were screened at baseline, 6 and 12 months. Full MetS in the ILMP group decreased by 26% (p < 0.001); in GA + Met group by 22.4% (p = 0.01) and in GA group by 8.2% (p = 0.28). The number of MetS components decreased significantly in the ILMP and GA + Met groups (mean change 0.81, p < 0.001 and 0.35, p = 0.05, respectively). Between-group comparison revealed a clinically significant decrease in MetS components in favor of the ILMP group (−0.58 (−0.88–0.28), p < 0.001). This study highlights the clinical potency of ILMP versus other diabetes prevention options in reducing MetS in Saudi adults with elevated fasting glucose.

While moderate to severe vitamin D deficiency is prevalent in Saudi Arabia, skeletal effects associated with this deficiency are not common in this population. In this interventional study we measured the effects of improving vitamin D status on bone biochemical markers in overweight and obese adult Saudis. A total of 47 volunteers (21 males, 26 females) out of the initial 95 subjects were given verbal advice to expose themselves to sunlight for 5–30 min twice weekly and were encouraged to increase their intake of vitamin D–rich foods. Serum 25(OH)D, osteocalcin, and type 1 collagen cross-linked C-telopeptide (CTx), were measured at baseline and after one year. A significant decrease in the prevalence of vitamin D deficiency was observed (44% to 27%) after one year follow-up (p = 0.025). Also, a parallel significant increase in osteocalcin and a decrease in CTX and osteoprotegerin were observed. The results suggest that a modest increase in vitamin D levels among overweight and obese subjects through the promotion of lifestyle changes for one year have marginal effects in bone turnover markers as well as obesity itself.