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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.

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  < 0.05) was observed. Whereas, triglycerides (r = 0.25, P  < 0.01), waist circumference (WHR) (r = 0.17, P  < 0.05) and CRP (r = 0.24, P  < 0.01) were all significantly and positively associated with ZAG. Circulating ZAG is associated with MetS in an age-dependent manner. Serum ZAG is a potential biomarker for MetS.

Spexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body-weight regulatory functions, we aimed to determine whether lifestyle intervention programs on weight loss and fasting glucose (FG) improvement among people with impaired glucose regulation also alter levels of circulating SPX. A total of 160 Saudi adult males and females with prediabetes were randomly selected from a larger cohort (N = 294) who underwent a 6-month lifestyle modification program to improve their glycemic status. Participants were split into two groups based on differences in glucose levels post-intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured at baseline and after 6 months. Changes in SPX was significant only in the improved group [baseline: median (Q1–Q3) of 164 pg/ml (136–227) vs follow-up: 176 pg/ml (146–285); p < 0.01]. When stratified by sex, the significant increase was observed only in females [159 pg/ml (127–252) vs 182.5 (152,369.1); p < 0.01]. Furthermore, SPX levels showed a significant inverse association with FG (β = −0.22, p = 0.003) even after adjustment with age and BMI, again only in females. Circulating SPX levels increase over time in people with prediabetes, particularly women who responded favorably in a 6-month lifestyle intervention program. Whether an unknown mechanism regulating the sexual disparity seen in SPX levels post-intervention exists should be further investigated using a larger sample size.

Prediabetes is a reversible, intermediate stage of type 2 diabetes mellitus (T2DM). Lifestyle changes that include healthy diet and exercise can substantially reduce progression to T2DM. The present study explored the association of 37 T2DM- and obesity-linked single nucleotide polymorphisms (SNPs) with prediabetes risk in a homogenous Saudi Arabian population. A total of 1129 Saudi adults [332 with prediabetes (29%) and 797 normoglycemic controls] were randomly selected and genotyped using the KASPar SNP genotyping method. Anthropometric and various serological parameters were measured following standard procedures. Heterozygous GA of HNF4A-rs4812829 (0.64; 95% CI 0.47–0.86; p < 0.01), heterozygous TC of WFS1-rs1801214 (0.60; 95% confidence interval (CI) 0.44–0.80; p < 0.01), heterozygous GA of DUSP9-rs5945326 (0.60; 95% CI 0.39–0.92; p = 0.01), heterozygous GA of ZFAND6-rs11634397 (0.75; 95% CI 0.56–1.01; p = 0.05), and homozygous AA of FTO-rs11642841 (1.50; 95% CI 0.8–1.45; p = 0.03) were significantly associated with prediabetes, independent of age and body mass index (BMI). Additionally, C-reactive protein (CRP) levels in rs11634397 (AA) with a median of 5389.0 (2767.4–7412.8) were significantly higher than in the heterozygous GA genotype with a median of 1736.3 (1024.4–4452.0) (p < 0.01). In conclusion, only five of the 37 genetic variants previously linked to T2DM and obesity in the Saudi Arabian population [HNF4A-rs4812829, WFS1-rs1801214, DUSP9-rs5945326, ZFAND6-rs11634397, FTO-rs11642841] were associated with prediabetes susceptibility. Prospective studies are needed to confirm the potential clinical value of the studied genetic variants of interest.

Angiopoietin-like protein 8 (ANGPTL8) has a role in lipid metabolism, beta-cell proliferation and diabetes progression, however, the association between different variants in the ANGPTL8 gene and metabolic syndrome (MetS) components has not been studied widely especially in Arab ethnic groups. In this study, the associations of ANGPTL8 variants on MetS risk in Saudi Arab adults were investigated. A total of 905 unrelated Saudi adults (580 healthy controls and 325 MetS) were included. MetS was screened based on the International Diabetes Federation (IDF) criteria. The genotype and allele frequency distribution of rs737337 (T/C) and rs2278426 (C/T) polymorphism in ANGPTL8 gene was studied. Participants with MetS were significantly older, had higher BMI, and rs737337 polymorphism frequency was significantly lower than in control. Furthermore, the TC + CC genotype and C allele of rs737337 (T/C) was associated with decreased risk of hypercholesterolemia and hyperglycemia [odds ratio (OR) 0.61, 95%CI 0.40–0.93, p = 0.016 and OR 0.58, 0.39–0.86, p = 0.007 respectively for hypercholesterolemia; and OR 0.66, 0.45–0.97, p = 0.032 and OR 0.65, 0.46–0.93; p = 0.016 respectively for hyperglycemia]. Similarly, CT, CT + TT genotype and T allele of rs2278426 (C/T) were associated with decreased risk of hyperglycemia (p < 0.05). In conclusion, the study suggests that the gene variants in SNPs rs 737337 (T/C) and rs 2278426 (C/T) are associated with lower risk of hypercholesterolemia and hyperglycemia. These findings supplement the growing literature supporting the role of ANGPTL8 in lipid and glucose metabolism.

Background Obesity has been linked to many adverse health consequences, including breast cancer. This study aims to determine adipocytokine and other biological changes in recently diagnosed breast cancer patients before therapy is started. Methods A total of 109 female Saudi subjects [56 newly diagnosed, treatment-naïve, histologically-confirmed breast cancer cases and 53 age- and BMI-matched controls] were enrolled in this study. Anthropometric data were collected. Serum insulin, adipocytokines and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured using a customized multiplex Luminex assay. Hypersensitive C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and angiotensin II (ANG II) were measured using ELISA. Results A few days in the diagnosis, breast cancer subjects had significantly higher systolic blood pressure ( p  = 0.03), glucose ( p  = 0.01), triglycerides ( p  = 0.001), leptin ( p  = 0.044), resistin ( p  = 0.04), ANG II ( p  = 0.02), TNF-α ( p  = 0.045), and CRP ( p  = 0.04) than the controls. On the other hand, HDL ( p  = 0.01) and adiponectin ( p  = 0.02) were significantly lower in cancer subjects than controls. A significant association was found between elevated triglycerides (TG) and breast cancer [OR (95% CI), 6.1(1.8, 15.6), p  = 0.004], as well as elevated ANG II [OR (95% CI), 5.2(1.2, 14.3), p  = 0.03]. On the other hand, aPAI and HDL correlated negatively with breast cancer [OR (95% CI), 0.076(0.01, 0.34), p  = 0.001; 0.30(0.09, 0.95), p 0.04, respectively]. Conclusion Circulating ANGII and triglycerides were positively associated with early breast cancer. In contrast, HDL-cholesterol correlated negatively with ANG II and aPAI in these patients. This suggests that patients with recently diagnosed breast cancer have biochemical changes consistent with an activated stress response and/or that patients with metabolic syndrome manifestations have a higher risk of developing this disease.

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.

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.

Obesity, commonly measured as body mass index (BMI), has been on a rapid rise around the world and is an underlying cause of several chronic non-communicable diseases, including type 2 diabetes mellitus (T2DM). In addition to the environmental factors, genetic factors may also contribute to the ongoing obesity epidemic in Saudi Arabia. This study investigated the association between variants of 36 previously established T2DM SNPs and obesity phenotypes in a population of Saudi subjects. Study subjects consisted of 975 obese (BMI: ≥30), 825 overweight (25–30) and 423 lean controls (18–25) and of these 927 had a history of T2DM. Subjects were genotyped for 36 SNPs, which have been previously proved to be T2DM linked, using the KASPar method and the means of BMI and waist circumference (WC) corresponding to each of the genotypes were compared by additive, recessive and dominant genetic models. Five and seven of 36 T2DM-related SNPs were significantly associated with the BMI and WC, respectively. Variants of SNPs rs7903146, rs1552224 and rs11642841 in the control group and rs7903146 in T2DM group showed significant association with both BMI and WC. Variant of SNP rs10440833 was significantly associated with BMI in T2DM group of both males [OR = 1.8 (1.0, 3.3); P  = 0.04] and females [OR = 2.0 (1.0, 3.9); P  = 0.04]. Genetic risk scores explained 19 and 14 % of WC and hip size variance in this population. Variants of a number of established T2DM related SNPs were associated with obesity phenotypes and may be significant hereditary factors in the pathogenesis of T2DM.

•Vitamin D deficiency is common in the Middle East.•Response to Vitamin D supplementation is genetically influenced.•SNPs in GC gene can predict response to vitamin D supplementation.•Carriers of rs4588/rs7041 in GC had lowest response to vitamin D supplementation. The aim of this study was to determine the influence of vitamin D–binding protein (DBP) gene polymorphisms in vitamin D metabolites before and after vitamin D supplementation. In all, 234 participants (126 women; 108 men) with vitamin D deficiency [25(OH)D <50 nmol/L] were given 50 000 IU of vitamin D supplements for 8 wk followed by daily maintenance of 1000 IU for 4 mo. Two single-nucleotide polymorphisms (rs4588 and rs7041) in DBP coding gene were assessed. Baseline 25(OH)D was significantly in higher in participants with homozygous major genotype of rs7041 than other genotypes (P = 0.02). Postsupplementation 25(OH)D was significantly higher in participants with homozygous major genotypes of either rs4588 and rs7041 than other genotypes (P < 0.001). Participants with the minor allele of either rs4588 or rs7041 were 2.9 (1.9–4.5) times and 3.7 (2.1–6.6) times, respectively, more likely to be non-responders (postsupplementation 25 OHD <50 nmol/L) than those homozygous for the major allele at these locations (P < 0.001). Furthermore, participants with homozygous minor and heterozygous genotype of rs7041 were 6.2 and 4.2times more likely to be non-responders than those with the homozygous major genotype (P < 0.001) even after adjustments for age, sex, body mass index, baseline 25(OH)D concentration, and other alleles. Participants with homozygous minor and heterozygous genotypes of rs4588 were 4.1 and 12.4times more likely to be non-responders than those with homozygous major genotypes. These significant risks, however, were lost after adjustment. rs7041 and rs4588 variants of the DBP gene are associated with variations in 25(OH)D levels and efficacy of response to vitamin D supplementation in Saudi Arabian adults.