Association of VDR gene variant rs2228570-FokI with gestational diabetes mellitus susceptibility in Arab women.

Gestational diabetes mellitus (GDM) has been linked with adverse pregnancy outcomes. Vitamin D receptor (VDR) gene variants have been associated with diabetes mellitus susceptibility and related complications. This study assessed the association between VDR gene polymorphism (rs2228570) and GDM risk among pregnant Arab women. A total of 368 pregnant Saudi women who were screened for GDM at 24-28 weeks of gestation and genotyped for the VDR gene variant (rs2228570) were included in this cross-sectional study. Circulatory insulin levels, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and vitamin D (25(OH)D) were measured. There were 108 women with GDM and 260 women without GDM. The genotype frequency of women with GDM was CC 60.2 %, CT 33.3 %, TT 6.9 %, and CT + TT 39.8 %; for non-GDM women, were CC 61.1 %, CT 31.5 %, TT 6.9 %, and CT + TT 38.4 %. No association was found between the VDR gene variant (rs2228570-FokI) and GDM susceptibility after adjustment for covariates. Serum 25(OH)D had a significant inverse association with FBG (r = -0.49, p = 0.01) and HbA1c (r = -0.45, p = 0.03) among carriers of the TT-genotype. Furthermore, a significant inverse correlation was observed between serum 25(OH)D and HOMA-ß (r = -0.20, p = 0.035) in individuals with the T-allele. Among pregnant Saudi women, glycemic indices appear to be influenced by vitamin D, suggesting a possible role it may play in mitigating the metabolic changes associated with GDM, particularly among individuals with specific genetic backgrounds. In our study population, rs2228570-FokI did not appear to be a significant contributor to GDM risk.

Hepatokines fetuin A and fetuin B status in women with/without gestational diabetes mellitus.

OBJECTIVES: To assess circulating fetuin A and fetuin B levels in participants with and without Gestational Diabetes Mellitus (GDM) and to find out their correlations with other different parameters relating to gestational diabetes in Saudi women. METHODS: A total of 123 Saudi pregnant women (N: 46 GDM and N: 77 healthy control) were included in this observational study. Fasting blood samples were collected to assess serum lipids, insulin and fetuin A and fetuin B. Serum fetuin A and fetuin B were quantified by commercially available kits. RESULTS: The median value of fetuin A was slight lower in GDM patients [2003 pg/ml (866-3369)] than in the control group [2015 pg/ml (1060-2951)] without significant difference (P=0.95). The median value of fetuin B was also slight lower in GDM patients [3292 ng/ml (782-6740)] than the control group [3514 ng/ml (364-14854)] but without significant difference (P=0.564). There was a significant inverse correlation between fetuin B and total cholesterol in control group. CONCLUSIONS: The present study did not find a significant association between fetuins A and B with GDM or insulin resistance, but there was a significant inverse correlation between fetuin B and total cholesterol in the control group, reflecting good glucose control and adequate use of lipids in the nutrition of the fetus. Further research is required in the future to understand fetuin's role in the progression of GDM in Saudi women.

Sex-Specific Cut-Offs of Single Point Insulin Sensitivity Estimator (SPISE) in Predicting Metabolic Syndrome in the Arab Adolescents.

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.

Associations of Perilipin 3 with Insulin Resistance in Arab Adults with Type 2 Diabetes.

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.

Vitamin D level and its relation to muscle and fat mass in adult male Arabs.

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) N = 325 (69.9%) and sufficient (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 < 0.05), while a significant inverse correlation between 25(OH)D and lean/height2, lean-arms-legs, lean-arms-legs/height2, fat (%) region, fat arms, fat legs, fat trunk, lean legs were noted. In conclusion, low circulating 25(OH)D is associated with enhanced fat infiltration in muscle tissues of adult Arab males.

The association between iron and vitamin D status in Arab adolescents.

OBJECTIVE: Both vitamin D and Fe micronutrient deficiencies are common in Saudi Arabia but the association between them is unclear. The present study aimed to determine whether Fe indices are associated with vitamin D status and other metabolic markers in Arab adolescents. DESIGN: Single-centre, cross-sectional study gathering anthropometrics, glucose and lipid profile. Serum 25-hydroxyvitamin D (25(OH)D), Fe, total iron-binding capacity (TIBC), transferrin saturation (%) and other parameters were measured. SETTING: Vitamin D School Project Database, King Saud University (2014-2016). PARTICIPANTS: Arab adolescents aged 10-17 years randomly selected from the Vitamin D School Project Database (170 Saudi students; 100 girls, seventy boys). RESULTS: Among Fe indices, only TIBC was found to be significantly and inversely associated with 25(OH)D (r = -0·20; P < 0·01) and only in girls (r = -0·20; P < 0·05). Among cardiometabolic parameters, serum Fe was associated with TAG in boys (r = 0·36; P < 0·01) and inversely associated with HDL-cholesterol in girls (r = -0·29; P < 0·05). Age was the most significant predictor of serum Fe for all participants, accounting for 5 % (R2 = 0·05; P = 0·004) of variance perceived. Serum 25(OH)D and age, on the other hand, were the most significant predictors for TIBC, accounting for 10·1 % (R2 = 0·10; P < 0·001) of variance perceived. CONCLUSIONS: Among healthy Arab adolescents, the association between vitamin D and Fe indices, particularly TIBC, is modest, inverse and sex-dependent. Larger studies with inclusion of markers such as hepcidin and ferritin, vitamin D metabolites and endogenous sex hormones may provide a clearer view of this complex association.

The plant flavonoid, fisetin alleviates cigarette smoke-induced oxidative stress, and inflammation in Wistar rat lungs.

In the present study, we tested the antioxidant and anti-inflammatory potential of the plant flavonoid, fisetin against cigarette smoke-induced oxidative stress, and inflammation in rat lungs. Male Wistar rats were chronically exposed to cigarette smoke (CS) with or without administration of fisetin. Fisetin administration to CS-exposed rats resulted in a significant reduction in neutrophils and macrophages in bronchoalveolar lavage fluid as well as malondialdehyde, 3-nitrotyrosine, 8-isoprostane, tumor necrosis factor-alpha, interleukin-1beta, granulocyte macrophage-colony stimulating factor, interleukin-4, and interleukin-10 levels in lung tissues compared to those in CS-exposed rats not treated with fisetin. Fisetin also significantly augmented lung hemoxinase-1, glutathione peroxidase-2, reduced glutathione, superoxide dismutase, nitric oxide, and nuclear factor erythroid 2-related factor (Nrf2) levels in CS-exposed rats. In addition, a marked reversal in CS-induced histopathological changes was noted in fisetin-treated rats. Collectively, these data demonstrate the potential of fisetin to blunt CS-induced oxidative stress and inflammation in the lung and to prevent tissue damage via the Nrf2-mediated upregulation of antioxidant gene expression. PRACTICAL APPLICATIONS: In the present study, we found that the plant flavonoid, fisetin significantly abrogated the oxidative stress, inflammation, and tissue damage induced by cigarette smoke, a powerful pro-oxidant in rat lungs. Additionally, fisetin markedly reversed cigarette smoke-induced increases in neutrophil and macrophage cell populations in bronchoalveolar lavage fluid. These findings are particularly significant considering the association of cigarette smoking with increased oxidative stress and inflammation, which are central to the pathologies of a wide variety of chronic diseases including chronic obstructive pulmonary disease, cancer, and cardiovascular diseases. Therefore, the present work underscores the beneficial effects of the regular consumption of plant-based foods with medicinal properties for the effective prevention of these chronic diseases.

The association of serum 25-OH vitamin D with asthma in Saudi adults.

The study aimed to assess the differences and associations of serum 25 (OH)D levels in Saudi adults with and without asthma. A total of 1070 Saudi adults aged 22 to 28 years (359 with known asthma and 711 matched nonasthmatic controls) were selected randomly from the Riyadh Cohort, Saudi Arabia. Serum 25(OH)D serum levels were measured. Asthma diagnosis was taken from questionnaires. In all participants, 359 (33.6%) were known asthmatic and 711 (66.5%) were nonasthmatic. The overall incidence of vitamin D deficiency (serum 25(OH)D <25 nmol/L) was 29.6% in controls and 35.6% in asthma group (P = .01). The asthma group have a significantly lower serum 25(OH)D than the control group (P = .01) but lost significance after adjusting for age, body mass index (BMI), and sex. Nonasthmatic and asthmatic females had a higher incidence of vitamin D deficiency (33% and 46%) than nonasthmatic and asthmatic males (17% and 33%). Vitamin D deficiency is significantly high among Saudi adults with asthma, but more so among women. Whether vitamin D deficiency exacerbates asthma attack remains to be proven in this population.

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus.

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 ß (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 < .01) and IL1ß (R = 0.41; p < .01). Stepwise regression analysis also suggested that IL1ß, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILß warrants further investigation as to the role of SPX in immune modulation.

IGF and IGFBP as an index for discrimination between vitamin D supplementation responders and nonresponders in overweight Saudi subjects.

Vitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25(OH)D level <50 nmol/L), aged 40.4 ±â€Š11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population.

Effects of Different Dietary and Lifestyle Modification Therapies on Metabolic Syndrome in Prediabetic Arab Patients: A 12-Month Longitudinal Study.

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.

Efficacy of Vitamin D interventional strategies in saudi children and adults.

Despite the amount of sunshine in Saudi Arabia, vitamin D (25(OH)D) deficiency is highly prevalent among Saudis. Several strategies are known to improve 25(OH)D status. The aim of this study was to evaluate the efficacy of different interventional strategies in improving 25(OH)D status in Saudi children and adults. This interventional study was undertaken among 593 out of 1152 Saudi subjects [530 students (aged 13-17 years) and 63 teachers (aged 26-46 years)] over a 6-month period from different secondary schools in Riyadh, Saudi Arabia. 25(OH)D status was taken at baseline and after 6 months post interventions. Subjects were divided into 3 groups and requested to implement different vitamin D correction schemes: sun-exposure, vitamin D-fortified milk consumption, and oral vitamin D supplementation (1000IU/day). Follow-up results revealed that all correction strategies used could decrease the deficiency of serum 25(OH)D with different potencies, with the highest positive percentage change observed in oral supplementation in both adults and children (11% men, 17% women, 16% boys and 8% girls). The oral vitamin D supplementation strategy also showed significant positive associations between delta (Δ) changes and HDL-cholesterol in both adults and children. In conclusion, oral vitamin D supplementation was the most effective strategy in improving vitamin D status in Saudi adults and children than sunlight exposure or consumption of vitamin D-fortified dairy products.

Sex-specific expression of apolipoprotein levels following replenishment of vitamin D.

Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency [25(OH)D < 50nmol/l] were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ±â€¯16.5nmol/l at end of study vs. 32.5 ±â€¯10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.

Parathyroid hormone in relation to various vitamin D metabolites in adult females.

Vitamin D binding protein (DBP) and albumin are the important determinants of circulatory 25(OH)D in adults. Physiological function of vitamin D is particularly regulated by DBPs. Serum parathyroid hormone (PTH) is considered as the biological activity reader of circulating 25(OH)D. We therefore examined the relationships between serum total, free, and bioavailable 25(OH)D versus PTH in apparently healthy Saudi female adults.A total of 350 apparently healthy Saudi female adults ([Mean ±â€Šstandard deviation] age [years] 52.9 ±â€Š9.2; body mass index [kg/m] 32.9 ±â€Š5.4) were included in this observational study. Anthropometrics was measured as well as fasting glucose, lipid profile, calcium and phosphorous using routine methods. Serum 25(OH)D was measured using an electrochemiluminescence immunoassay. Serum DBP was determined by ELISA. Free and bioavailable 25(OH)D were calculated by comparing concentrations of total 25(OH)D, DBP, and albumin.Data revealed that circulating total 25(OH)D had weak but significant inverse association with DBP (R = -0.24; P < .01), and strong inverse associations with free 25(OH)D (R = -0.87; P < .001), albumin-bound 25(OH)D (R = -0.88; P < .001), and bioavailable 25(OH)D (R = -0.89; p < 0.001). None of the vitamin D metabolites, including 25(OH)D, correlated with serum PTH.Various metabolites of 25(OH)D are not correlated with serum PTH in Saudi adult females. Bioavailable, albumin-bound and free 25(OH)D cannot be surrogate measures for vitamin D status, at least in this population.

Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Saudi Type 2 Diabetic Patients.

This study aimed to investigate whether uric acid to creatinine (UA/Cr) ratio is associated with higher risk of metabolic syndrome (MetS) and its components. 332 adult Saudi type 2 diabetes mellitus (T2DM) patients were divided into UA/Cr tertiles. Risk for full MetS was significantly highest in individuals that constitutes the uppermost serum UA/Cr tertile [Odds ratio (OR): 1.80, 95% confidence interval (CI): 1.0-3.3; p < 0.001) after adjustment for age, gender and BMI. Similarly, risk for individual components of MetS like central obesity, hypertriglyceridemia, low HDL-cholesterol and hypertension was significantly highest in this tertile with OR's of 2.61 (1.2-5.6), 1.42 (0.7-2.3), 1.45 (0.7-2.8) and 1.16 (0.6-2.2) respectively (all p-values < 0.001) after adjustment for age, gender, BMI and other components of MetS. Furthermore, serum UA/Cr levels increased with increasing number of MetS components (mean values of 4.44, 4.49, 4.64, 4.89 and 4.91 respectively for 1,2,3,4 and 5 MetS components, p-values < 0.001 after adjusting for age, gender and BMI). Our data suggest that serum UA/Cr in T2DM patients is strongly associated with full MetS as well as its individual components. These findings are of considerable clinical importance as serum UA/Cr may be used as a marker in the pathogenesis of MetS.

Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients.

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 ß-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.

Gender-Specific Association Between FGFR4 Gly388Arg Gene Variants and Hypertension.

AIMS: Variations in fibroblast growth factor (FGF) levels have been associated with alterations in blood pressure. FGFs mediate their function through binding to their FGF receptor (FGFR). The FGFR4 Gly388Arg polymorphism is associated with cancer and cardiovascular diseases, but its association with hypertension is unclear. Here, we aimed to investigate the association between the FGFR4 Gly388Arg polymorphism and hypertension. MATERIALS AND METHODS: Three hundred Saudi individuals (150 normotensive controls and 150 hypertensive subjects) were genotyped for the FGFR4 Gly388Arg (G/A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method. Anthropometrics, glucose and lipid profiles were measured for all subjects. The frequency of the FGFR4 Arg388 (A) allele was significantly higher in hypertensive subjects (36%) than controls (24.3%) (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.5-3.83, p < 0.001). In addition, GA (OR 2.51, 95% CI 1.3-4.85, p = 0.006), AA (OR 5.58, 95% CI 1.79-11.8, p = 0.003), and GA + AA (OR 2.91, 95% CI 1.55-5.46, p = 0.001) genotypes were significantly associated with the risk of hypertension, even after adjusting for age, body mass index, and glucose. Gender stratification showed a significant association only in female subjects (p < 0.001). Furthermore, subjects with GA and AA genotypes showed significantly higher diastolic blood pressure than those with GG genotype (p = 0.004). CONCLUSION: The FGFR4 Arg388 allele is associated with an increased risk of hypertension in Saudi female subjects. The lack of association in men needs to be further investigated.

Susceptibility to type 2 diabetes may be modulated by haplotypes in G6PC2, a target of positive selection.

BACKGROUND: The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the common terminal reaction in the gluconeogenic/glycogenolytic pathways and plays a central role in glucose homeostasis. In most mammals, different G6PC subunits are encoded by three paralogous genes (G6PC, G6PC2, and G6PC3). Mutations in G6PC and G6PC3 are responsible for human mendelian diseases, whereas variants in G6PC2 are associated with fasting glucose (FG) levels. RESULTS: We analyzed the evolutionary history of G6Pase genes. Results indicated that the three paralogs originated during early vertebrate evolution and that negative selection was the major force shaping diversity at these genes in mammals. Nonetheless, site-wise estimation of evolutionary rates at corresponding sites revealed weak correlations, suggesting that mammalian G6Pases have evolved different structural features over time. We also detected pervasive positive selection at mammalian G6PC2. Most selected residues localize in the C-terminal protein region, where several human variants associated with FG levels also map. This region was re-sequenced in ~560 subjects from Saudi Arabia, 185 of whom suffering from type 2 diabetes (T2D). The frequency of rare missense and nonsense variants was not significantly different in T2D and controls. Association analysis with two common missense variants (V219L and S342C) revealed a weak but significant association for both SNPs when analyses were conditioned on rs560887, previously identified in a GWAS for FG. Two haplotypes were significantly associated with T2D with an opposite effect direction. CONCLUSIONS: We detected pervasive positive selection at mammalian G6PC2 genes and we suggest that distinct haplotypes at the G6PC2 locus modulate susceptibility to T2D.

Calculated adiposity and lipid indices in healthy Arab children as influenced by vitamin D status.

BACKGROUND: Both childhood obesity and vitamin D deficiency are common in the Middle East. This study aims to determine whether the associations of vitamin D status to traditional anthropometric parameters hold true for nonconventional measures of adiposity, such as body adiposity index (BAI), a measure of body fat percentage, waist-to-hip ratio, waist-to-height ratio (WHtR), and lipid indices, in apparently healthy Arab children. METHODS: A total of 4183 apparently healthy Saudi school students (1906 boys; 2277 girls) aged 12 to 17 years were recruited in this cross-sectional study. Anthropometrics were obtained. Fasting blood glucose and lipids were measured routinely. Serum 25(OH)D was measured using chemiluminescence. RESULTS: In all subjects, age, BAI, waist-to-hip ratio, and high-density lipoprotein cholesterol (HDL-C) accounted for 4% of the variance in serum 25(OH)D (P < .001). All adiposity indices were inversely associated with 25(OH)D, with WHtR being the most inferior in terms of strength of association. Vitamin D deficiency significantly increased risk for low HDL-C in all subjects (odds ratio [95% confidence interval]: 1.70 [1.24-2.3]; P < .001). CONCLUSION: BAI is significantly associated with 25(OH)D levels in Arab children. WHtR is inferior than other anthropometric measures of obesity regarding the strength of association with 25(OH)D. Risk for or low HDL-C is significantly increased with vitamin D deficiency. Interventional studies may determine the potential cardioprotective effects of vitamin D correction in this population.

Association of Vitamin B12 with Pro-Inflammatory Cytokines and Biochemical Markers Related to Cardiometabolic Risk in Saudi Subjects.

BACKGROUND: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. METHODS: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. RESULTS: Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05). CONCLUSIONS: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.