Hossam M. Draz

Metabolic syndrome biomarkers and early breast cancer in Saudi women: evidence for the presence of a systemic stress response and/or a pre-existing metabolic syndrome-related neoplasia risk?

BackgroundObesity 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.MethodsA 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.ResultsA 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].ConclusionCirculating 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.

Vitamin D Receptor Gene Polymorphisms and HLA DRB1*04 Cosegregation in Saudi Type 2 Diabetes Patients

The vitamin D receptor (VDR) gene has been involved in the modulation of susceptibility to inflammatory and autoimmune conditions, and could play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Susceptibility to T2DM was recently also suggested to associate with HLA alleles. We evaluated possible correlations between VDR polymorphisms, HLA alleles, and risk for development of T2DM by analyzing 627 individuals (368 T2DM patients and 259 healthy control subjects) part of a well-characterized cohort followed in Riyadh, Kingdom of Saudi Arabia. Genomic DNA was genotyped for the VDR gene single nucleotide polymorphisms of Fok-1, Taq-1, ApaI, and Bsm-I. Analyses were run by allelic discrimination real-time PCR. HLA genotyping was performed as well by PCR using sequence-specific primers, whereas cytokine production was evaluated by FACS. Results showed T2DM to be significantly associated with the VDR Taq1 (rs731236-AG) and Bsm-I (rs1544410-CT) genotypes, and the VDR rs1544410-T allele. Cosegregations resulting in significant increases of T2DM odds ratio were detected between Taq1 and Bsm-I VDR polymorphisms and HLA DRB1*04. Notably, the VDR polymorphisms observed to be more frequent in T2DM patients correlated with increased VDR expression and IL-12 production, as well as with metabolic parameters of susceptibility to T2DM, including serum cholesterol and high-density lipoprotein levels. VDR polymorphisms are present in T2DM, and correlate with HLA DRB1*04 and with immunologic and metabolic parameters; results from this study add T2DM to the list of diseases that are likely modulated by an HLA/VDR interaction.

Soluble CD163 is associated with body mass index and blood pressure in hypertensive obese Saudi patients

Eur J Clin Invest 2012; 42 (11): 1221–1226

Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to body weight regulation.

Loss and disproportionate gain of body weight often seen respectively in smokers and quitters are believed to be due to disrupted energy homeostasis induced by nicotine, the major constituent of cigarette smoke. Energy homeostasis is suggested to be regulated by the coordinated actions of peripheral adipose tissue derived leptin and the brain hypothalamic orexigenic neuropeptide Y (NPY). While the studies probing the role of leptin and NPY in weight modulating effect of nicotine have so far been inconsistent and based largely on animal systems, there is a paucity of data involving human subjects. Here we measured the plasma levels of orexigenic neuropeptide Y (NPY) and leptin in 35 non-smokers and 31 cigarette smokers before and three months after smoking cessation. Compared to non-smokers, smokers were leaner and had reduced NPY and leptin levels. Smoking cessation resulted in a significant weight gain and increased waist circumference accompanied by increased leptin and NPY levels. NPY levels were significantly correlated with body weight (r=0.43, p<0.05), BMI (r=0.41, p<0.05), and waist circumference (r=0.37, p<0.05), while leptin correlated with BMI (r=0.42, p<0.05) and waist circumference (r=0.39, p<0.05). Association of leptin with smoking status, but not that of NPY, was lost after controlling for anthropometric parameters. Weight modulating effect of cigarette smoke may thus involve its direct action on NPY, independent of leptin. Altered leptin levels in smokers and quitters may merely reflect changes in body weight or precisely fat mass.

Long‐term exposure to incense smoke alters metabolism in Wistar albino rats

The burning of incense is an important source of indoor air pollution in Asia. We assessed the effect of long‐term exposure to incense smoke on the body weight and levels of circulating glucose, triglycerides, total cholesterol, HDL‐cholesterol, insulin, adiponectin and leptin in Wistar albino rats. Two groups of rats were used. First group (n = 12) was exposed daily to incense smoke for 4 months at the rate of 4 g day−1 in the exposure chamber. Another group of rats (n = 12), was used as non‐exposed control. Blood samples were collected from all animals after 4, 8, 12 and 16 weeks of exposure. Serum glucose, triglycerides, total cholesterol and HDL‐cholesterol, LDL‐cholesterol insulin, adiponectin and leptin were measured. Our results showed that incense smoke exposure was associated with decreased weight gain and the adverse metabolic changes of increased triglycerides and decreased HDL‐cholesterol concentrations. Exposure to incense was also associated with a transient increase of leptin levels. Taken together, these data suggest that incense smoke influences metabolism adversely in rats. The effect of incense smoke on human health and the underlying mechanisms need to be studied further. Copyright

Retinol Binding Protein-4 Is Associated with TNF-α and Not Insulin Resistance in Subjects with Type 2 Diabetes Mellitus and Coronary Heart Disease

We studied the association between RBP4 and various markers related to insulin resistance and diabetic complications as well as inflammatory markers in Saudi population suffering from type 2 diabetes and coronary heart disease. Patients with type 2 diabetes were divided into 3 groups according to the type of treatment and involvement of coronary artery disease. Serum RBP4, TNF-α, insulin, CRP, resistin, leptin and adiponectin were analysed in all samples. RBP4 levels increased significantly in the group of diabetic subjects treated with oral hypoglycemic agents and diabetic patients with coronary heart disease (30.2 ± 11.8; 33.4 ± 13.6 respectively), while there was no significant change in the other group for diabetic subjects on low-carbohydrate diet (25.1 ± 10.9) compared to control group (22.6 ± 9.5). RPB4 levels were positively correlated with TNF-α in the group of diabetic subjects on oral hypoglycemic agents and diabetic patients with coronary heart disease (r = 0.52, P < 0.05; r = 0.58, P < 0.05 respectively). No correlations were found between RBP4 levels and insulin resistance in all studied groups. Our findings suggest that serum RBP4 levels is associated with pro-inflammatory cytokine (TNF-α) and is not associated with insulin resistance among patients with type 2 diabetes and coronary heart disease.

Gender-specific associations between insulin resistance, hypertension, and markers of inflammation among adult Saudis with and without diabetes mellitus type 2.

PURPOSE In view of the important roles of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and the acute phase reactant C-reactive protein (CRP) in glucose metabolism and pathogenesis of diabetes mellitus type 2 (DMT2), we assessed gender-specific differences and relative associations of these inflammatory biomarkers to insulin resistance (IR) and risk markers for DMT2. MATERIALS AND METHODS Serum levels of TNF-α, IL-6 and CRP were determined in 119 clinically diagnosed DMT2 cases, 114 non-DMT2 subjects with IR, and 97 age-matched controls. Fasting blood samples were collected and serum glucose levels, lipid profile, and inflammatory markers were analyzed. RESULTS In women, a significant association between elevated levels of IL-6 and risk of developing IR [Odds ratio (OR), 4.389, 95 % Confidence Interval (CI) 1.6-11.52, p = 0.004] was found. Significant associations were also found between elevated levels of CRP and risk of hypertension only in female subjects [OR (95% CI) 2.153 (1.04-4.53), p = 0.046]. While, in male subjects, a significant association between elevated levels of TNF-α and risk of developing IR [OR (95% CI) 2.32 (1.09-4.93), p = 0.029] was found. CONCLUSION The present study showed apparent gender differences in the association of IL-6, CRP, and TNF-a with risks of IR and hypertension, and this could be attributed to sexual dimorphism in fat distribution.

Endothelial nitric oxide synthase gene polymorphisms (894G > T and -786T > C) and risk of coronary artery disease in a Saudi population.

BACKGROUND AND AIMS Endothelial nitric oxide synthase gene polymorphisms, either independently or through gene environmental interactions, are associated with cardiovascular diseases in multiple ethnic populations. However, no information is available with regard to such associations in a Saudi population despite a high incidence of cardiovascular abnormalities. We studied the associations of 894G>T and -786T>C polymorphisms of endothelial nitric oxide synthase gene with coronary artery disease in Saudi population. METHODS Variants 894G>T and -786T>C were studied in 142 coronary artery disease patients and 145 normal controls by PCR-restriction fragment length polymorphism analysis and allele specific PCR, respectively. RESULTS Carriers of GT and TT genotypes of 894G>T polymorphism were significantly high (p <0.0001) in patients (47.2 and 7%, respectively) than in controls (27.6 and 4.8%, respectively). Likewise, carriers for TC and CC genotypes of -786T>C polymorphism were significantly high (p <0.001) in patients (50 and 32% respectively) than in controls (34.5 and 22.5% respectively). Both 894G>T [OR (95% CI); 4.39 (1.69-11.42)] and -786T>C [OR (95% CI); 2.74 (1.02-7.32]) variants were independently associated with the disease status. Genotype distributions of 894G>T and -786T>C polymorphisms in the diseased and control populations matched with those found in Caucasian populations. CONCLUSION This study, for the first time, suggests an independent association of 894G>T and -786T>C polymorphisms of endothelial nitric oxide synthase gene with coronary artery disease in a Saudi population.

Urinary Iodine is Associated with Insulin Resistance in Subjects with Diabetes Mellitus Type 2

BACKGROUND Diabetes Mellitus (DM) is a major health problem worldwide and its prevalence in Saudi Arabia has reached 31.6%. Patients with diabetes mellitus are at an increased risk of thyroid disease. The purpose of this study was to examine the urinary excretion of iodine in type 2 DM (T2DM) patients, and to assess the clinical implication of iodine status on T2DM. METHODS A total of 266 adult Saudis aged 18-55 years (109 T2DM patients and 157 healthy controls) were randomly selected from the Riyadh Cohort Study. Subjects were assessed for anthropometry, morning blood chemistries including fasting glucose, and lipid profile; serum concentrations of leptin, adiponectin, resistin, insulin, aPAI, hsCRP, Ang II, TNF-α, TSH, T3, T4, urine creatinine, urine iodine were measured using specific assays. RESULTS The concentration of urine iodine was significantly lower in T2DM than in healthy control subjects (84.6±2.3 vs. 119.4±3.4, p<0.001), which remained significant after creatinine correction and controlling for age (p=0.01). Furthermore, urinary iodine is negatively correlated with waist, hips, SAD, glucose, insulin, HOMA-IR triglyceride, resistin, angiotensin II (Ang II), and CRP, while it was positively associated with TSH. CONCLUSIONS The decreased levels of iodine concentration in T2DM patients and its likely deleterious effects on metabolic functions calls for a systematic approach to thyroid disease screening in diabetic patients. Routine annual urinary iodine determination is recommended and should target T2DM patients at risk of thyroid dysfunction.

Association of body mass index, sagittal abdominal diameter and waist-hip ratio with cardiometabolic risk factors and adipocytokines in Arab children and adolescents

BackgroundSagittal abdominal diameter (SAD) is a novel anthropometric measure hypothesized to be a surrogate measure of visceral abdominal obesity in adults. This study aims to determine whether SAD is superior to other anthropometric measures such as body mass index (BMI) and waist to hip ratio (WHR) in terms of association to cardiometabolic risk and circulating adipocytokine concentrations in a cohort of Saudi children and adolescents.MethodsA total of 948 (495 boys and 453 girls) apparently healthy children with varying BMI, aged 10–17 years, were included in this cross sectional study. Fasting glucose, lipid profile, leptin, adiponectin, resistin, insulin, TNF-α and aPAI-1 were measured in serum and HOMA-IR was calculated. MetS components were defined according to the International Diabetes Federation (IDF) criteria.ResultsBMI was superior to SAD as well as WHR, and had the highest number of significant associations to MetS components and adipocytokines even after adjustment for age and gender, including blood pressure, lipids, glucose and leptin.ConclusionIn conclusion, while SAD is significantly associated with components of MetS among children and adolescents, it is not superior to BMI. The use of SAD therefore may not be practical for use in the pediatric clinical setting. Follow-up studies are needed to determine whether SAD has clinical significance in terms of harder outcomes such as predicting diabetes mellitus or cardiovascular diseases.