The association between hypertension and other cardiovascular risk factors among non-diabetic Saudis adults-A cross sectional study

Population specific associations between cardiovascular disease with various risk factors including pre-hypertension and hypertension were reported. We aimed to investigate the association of higher than optimal blood pressure with measures of dysglycemia, dyslipidemia, and markers of inflammation in non-diabetic Saudi adults hoping to improve current Saudi guidelines to prevent cardiovascular disease. Volunteers were recruited randomly from public healthcare centers in Jeddah. Demographic information, blood pressure (BP), and anthropometric measurements were taken. Fasting blood samples were drawn, then again following 1-hour oral glucose tolerance test. Glycated hemoglobin, fasting plasma glucose (FPG), lipid profile, highly sensitive C- reactive protein, gamma glutamyl transferase, and 1-hour plasma glucose were measured. Complete data was found for 742 men and 592 women. Pre-hypertension was found in 47.2% of men, and 24.7% of women, while 15.1% of men, and 14.6% of women were hypertensive. Means of measured variables differed significantly between normotensive, pre-hypertensive, and hypertensive groups of men and women in gender specific manner. Association between measured variables and elevated BP, and hypertension were assessed using logistic regression models. After adjustment for age, body mass index and waist circumference, elevated blood pressure was associated with elevated triglycerides in men, while hypertension was significantly associated with elevated fasting plasma glucose, total cholesterol, triglycerides, low density lipoprotein- cholesterol, and low high density lipoprotein- cholesterol in men, and elevated triglycerides, and total cholesterol in women. Therefore, it is strongly recommended to measure lipid profile, specifically TG, for all diagnosed pre-hypertensive and hypertensive patients in addition to FPG for men.Peer reviewe

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients

ABCA1 C69T Gene Polymorphism Association with Dysglycemia in Saudi Prediabetic Adults

Studies suggest that ATP-binding cassette transporter A1 (ABCA1 C69T) polymorphism is associated with a decreased incidence of type 2 diabetes mellitus (T2DM) and that there is an association between ABCA1 C69T polymorphism and the risk of dyslipidemia in diabetic individuals. However, other studies contradict these suggestions. Therefore, we aimed to investigate the prevalence of ABCA1 C69T (rs1800977) gene polymorphism in a representative sample of the Saudi population not previously diagnosed with diabetes and its possible association with dyslipidemia and dysglycemia. A cross-sectional design was used to recruit nondiabetic adults of both genders from the Saudi population in Jeddah by employing a stratified, two-stage cluster sampling method. A total of 650 people (337 men and 313 women) were recruited. Demographic, dietary, and lifestyle variables, as well as medical history and family history of chronic diseases, were collected using a predesigned questionnaire. Fasting blood samples were taken for the determination of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and lipids profile, which were followed by a 1-h oral glucose tolerance test (OGTT). Real-time PCR technology was used to determine the ABCA1 C69T gene SNP (rs1800977). The T allele of ABCA1 C69T (rs1800977) was very frequent (TT in 44.9% and CT in 43.7%). There was a trend toward significance for a higher dysglycemia percentage in people with CT and TT genotypes (25.7%, and 23.3%, respectively) compared with CC genotypes (16.2%). In addition, FPG and 1-h plasma glucose were significantly higher in people with both TT and CT genotypes compared to CC genotypes. However, T allele was not associated with any dysregulation of lipid parameters

Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC50 values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC50 values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects

Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

BACKGROUND: Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. HYPOTHESIS: Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. PROTOCOL: Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. RESULTS: In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). DISCUSSION: Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. CONCLUSIONS: Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk

Health Impact of Fasting in Saudi Arabia during Ramadan: Association with Disturbed Circadian Rhythm and Metabolic and Sleeping Patterns

Background: Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Hypothesis: Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Protocol: Ramadan practitioners (18 males, 5 females; mean age +/- SEM = 23.16 +/- 1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (+/- 1 hour) and again twelve hours later. Results: In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p&lt;0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Discussion: Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Conclusions: Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk

Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors

Background During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance. Aim To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1 alpha in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors. Methods Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 + 1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (+/- 1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1 alpha was evaluated in circulating leukocytes. Results Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1 alpha mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan. Discussion Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1 alpha mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus

Factors associated with adherence to Mediterranean diet among Saudi non-diabetic patients attending primary health care centers: A cross-sectional study

الملخص: أهداف البحث: للتحقيق في العوامل المسؤولة ودرجة الالتزام بحمية البحر الأبيض المتوسط بين المرضى غير المصابين بالسكري من مراجعي مراكز الرعاية الصحية الأولية. طرق البحث: أُجريت دراسة مستعرضة في مراكز الرعاية الصحية الأولية بجدة، بواسطة استبانة مصدقة ذاتية الاستخدام، تقوم بتقييم مستويات الالتزام لـ ١٤ جانبا غذائيا متعلقا بحمية البحر الأبيض المتوسط. تمكِّن الاستبانة من حساب درجة التزام (٠- ١٤)، في حين تم افتراض التزام غير كافي للنتائج ≥٧. وقد شملت عوامل الالتزام الخصائص الديموغرافية الاجتماعية العامة والتاريخ المَرَضي ونمط الحياة وعوامل الخطورة القلبية الوعائية مثل مؤشر كتلة الجسم ونسبة الخصر إلى الورك وضغط الدم والصيام ومستوى الجلوكوز في الدم بعد الأكل بساعة واحدة. النتائج: من بين المشاركين الـ ٢٦٥ (٥٠.٦٪ ذكورا)، سُجِّل عدم الالتزام الكافي في ٧٤.٣٪. وكانت درجات الالتزام أعلى في المشاركين المتزوجين (٦.٨٦ ± ١.٧٤مقابل ٦.٢٤ ± ١.٧٩) والممارسين للنشاط البدني المنتظم (٦.٧٩ ± ١.٩٠مقابل ٦.٣٠ ± ١.٦٣) بالمقارنة مع نظرائهم، على التوالي. علاوة على ذلك، فقد ازداد الالتزام بالحمية المتوسطية مع التقدم في العمر (معامل انحدار غير معياري=٠.٠٢ ومعامل ارتباط= ٠.١٣٣). ومن المثير للاهتمام، أنه لم ترتبط درجات الالتزام بعوامل الخطورة الرئيسة المتعلقة بالقلب والأوعية الدموية، فيما عدا الارتفاع البيّن في ضغط الدم الانبساطي بين المشاركين الملتزمين مقارنة بقرنائهم قليلي الالتزام (٧٧.٩٦± ١٢.٢٠مقابل ٧٤.٠١± ١٢.٢٤، على التوالي). الاستنتاجات: كان لواحد من أصل ٤ مرضى غير مصابين بداء السكري من الذين راجعوا مراكز الرعاية الصحية الأولية، التزام جيد بحمية البحر الأبيض المتوسط دون ارتباط يُذكر بعوامل الخطورة القلبية الوعائية. يُوصى بإجراء المزيد من الدراسات للتحقيق في الوعي والمعرفة حول النظام الغذائي المتوسطي بين السكان السعوديين، ومن بعدها يمكن تفصيل برامج التوعية وفقًا لذلك. Abstract: Objectives: To investigate the degree and factors responsible for adherence to a Mediterranean diet among non-diabetic patients attending primary health care centres (PHCCs). Methods: A cross-sectional study was conducted in Jeddah PHCCs using a validated self-administered questionnaire which assessed adherence levels to 14 dietary aspects related to the Mediterranean diet. The questionnaire enabled calculation of an adherence score (0–14), where inadequate adherence was assumed for scores ≤7. Factors of adherence included general socio-demographic characteristics, medical history, lifestyle, and cardiovascular risk factors such as body mass index, waist-to-hip ratio, blood pressure, and fasting and 1-h postprandial blood glucose levels. Results: Of the 265 participants (50.6% males), inadequate adherence was reported in 74.3%. Adherence scores were higher in married participants than in unmarried ones (6.68 ± 1.74 vs. 6.24 ± 1.79, p = 0.04), as well as in those who engaged in regular physical activity vs. those who did not (6.79 ± 1.90 vs. 6.30 ± 1.63, p = 0.02). Furthermore, Mediterranean diet adherence increased with age (B = 0.02, r = 0.133; p < 0.001). Interestingly, adherence scores were not associated with major cardiovascular risk factors except for a significantly higher diastolic blood pressure in participants with adequate as opposed to low adherence (77.96 ± 12.20 vs. 74.01 ± 12.24, respectively, p = 0.022). Conclusion: One out of 4 non-diabetic patients attending PHCCs exhibited good adherence to a Mediterranean diet without considerable association with cardiovascular risk factors. Further studies are recommended to investigate awareness and knowledge regarding the Mediterranean diet among Saudi populations. Subsequently, awareness programs could be tailored accordingly. الكلمات المفتاحية: حمية البحر الأبيض المتوسط, غير السكري, الالتزام, المملكة العربية السعودية, القلب والأوعية الدموية, Keywords: Adherence, Cardiovascular, KSA, Mediterranean diet, Non-diabete

HOMA-IR, and concentrations of adipokines, GH and other metabolic/inflammatory parameters during Shaaban and Ramadan.

<p>GH, Growth Hormone; TBil, total Bilirubin; ALKP, alkaline phosphatase; HOMA-IR, homeostasis model assessment of insulin resistance; GGT, gamma glutamyl transferase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TProt, total protein; hsCRP, high sensitivity C-reactive protein; Alb, albumin; (*), Reported earlier in ref 15, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096500#pone.0096500-Bahijri1" target="_blank">[15]</a>.</p