The prevalence of metabolic syndrome in patients receiving antipsychotics in Qatar: a cross sectional comparative study.

BACKGROUND: Metabolic abnormalities are common in patients maintained on antipsychotics. These abnormalities increase the risk of cardiovascular diseases and mortality in this population. The aim of this study is to assess the prevalence of metabolic syndrome (MetS) in subjects maintained on antipsychotics relative to controls in Qatar, and to assess the factors contributing to the development of MetS. METHODS: A cross sectional design was used to collect data and fasting blood samples from subjects maintained on antipsychotics for at least six months (n = 112) and from a control group (n = 114). The groups were compared in regard to prevalence of MetS, and multiple regression analysis was used to determine the risk factors in each group. RESULTS: The two groups (antipsychotics vs. control) were similar in regard to age (35.73 ± 10.28 vs. 35.73 ± 8.16 years) and gender ratio. The MetS was higher among the subjects on antipsychotics, but this difference did not reach statistical significance. Blood pressure (BP) was significantly higher in the antipsychotics group and BMI was the major risk factor to develop MetS in this group. CONCLUSIONS: The prevalence of MetS in both groups is high and mostly attributed to obesity and high BP. Public health interventions are needed to address this major health problem overall. Larger studies are needed to further assess the impact of antipsychotics and mental illness on the development of MetS.

iTRAQ-based quantitative protein expression profiling and MRM verification of markers in type 2 diabetes.

The pathogenesis of Type 2 diabetes mellitus (T2DM) is complex owing to molecular heterogeneity in the afflicted population. Current diagnostic methods rely on blood glucose measurements, which are noninformative with respect to progression of the disease to other associated pathologies. Thus, predicting the risk and development of T2DM-related complications, such as cardiovascular disease, remains a major challenge. We have used a combination of quantitative methods for characterization of circulating serum biomarkers of T2DM using a cohort of nondiabetic control subjects (n = 76) and patients diagnosed with T2DM (n = 106). In this case-control study, the samples were randomly divided as training and validation data sets. In the first step, iTRAQ (isobaric tagging for relative and absolute quantification) based protein expression profiling was performed for identification of proteins displaying a significant differential expression in the two study groups. Five of these protein markers were selected for validation using multiple reaction-monitoring mass spectrometry (MRM-MS) and further confirmed with Western blot and QPCR analysis. Functional pathway analysis identified perturbations in lipid and small molecule metabolism as well as pathways that lead to disruption of glucose homeostasis and blood coagulation. These putative biomarkers may be clinically useful for subset stratification of T2DM patients as well as for the development of novel therapeutics targeting the specific pathology.

Docosahexaenoic Acid Counteracts the Hypoxic-Induced Inflammatory and Metabolic Alterations in 3T3-L1 Adipocytes.

BACKGROUND: Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O2 tension are not well known. Consequently, this study aimed to evaluate the impact of DHA on markers of inflammation, metabolism, apoptosis, and oxidative stress in 3T3-L1 cell adipocytes exposed to low O2 tension (1% O2) induced hypoxia. METHODS: The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated. RESULTS: DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY). CONCLUSION: This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis.

The Immunophenotyping Changes of Peripheral CD4+ T Lymphocytes and Inflammatory Markers of Class III Obesity Subjects After Laparoscopic Gastric Sleeve Surgery - A Follow-Up Study.

PURPOSE: Obesity is a chronic disorder characterized by a low-grade inflammatory state and immune cell irregularities. The study aimed to follow up on the changes in the peripheral CD4+ T lymphocytes and the pro-inflammatory cytokines; IL-6, TNF-alpha, MCP-1, and IL-10 at baseline and 12 weeks post-surgical intervention by the laparoscopic gastric sleeve (LGS) in morbidly obese patients (class III obesity subjects). MATERIALS AND METHODS: A prospective longitudinal research included 24 class III obesity subjects with a BMI > 40 kg/m2. The subjects were enrolled from the Metabolic/Surgical Department at Hamad Medical Corporation (HMC)-Qatar. Fasting blood samples were collected at admission to LGS for weight loss and after 12 weeks of LGS. The immunophenotype of CD4+ T-cell populations; naïve (CD45RA+and CD27+), central memory T cells (CD45RO+ and CD27+), and effector memory (CD45RO+and CD27-) and T-regulatory cell (CD4+CD25+ FoxP3+) were identified using flow cytometry. Plasma pro-inflammatory cytokines and adipokines were evaluated. A control group of lean subjects was used to compare changes of T-regulatory and inflammatory biomarkers with postoperative changes in obese patients. RESULTS: The means (SD) of age and BMI of class III obesity subjects was 32.32 (8.36) years and 49.02 (6.28) kg/m2, respectively. LGS caused a significant reduction in BMI by 32%, p<0.0001. LGS intervention significantly decreased CD4+ T-lymphocytes and effector memory (TEM) cells but increased T-regulatory (Treg), naïve, and central memory (TCM) cells, with all p values < 0.05. The increase of Treg cells postoperative is significantly lower compared to lean subjects, p < 0.05. A significant reduction of plasma IL-6, TNF-α, and MCP-1, but IL-10 significantly increased after LGS, with all p<0.05. Adiponectin/leptin ratio improved after LGS by 2.9 folds, p<0.0001. CONCLUSION: Weight loss by LGS accomplished a substantial rise of Treg and decreased EM T-lymphocytes with a shift from pro-inflammatory to the anti-inflammatory pattern.

Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus.

OBJECTIVE: The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers. METHODS: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database. RESULTS: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers. CONCLUSION: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities.

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.

BACKGROUND: Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS). METHODS: We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing coronary angiography for ACS. Patients were divided into group A (ACS with insignificant stenosis (<50%)) and group B (with significant stenosis (≥ 50%)). RESULTS: Patients carrying the minor G allele in rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM, P = 0.026) than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM, P = 0.004) than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30-0.92), P = 0.038, among patients with significant stenosis. CONCLUSIONS: Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated with LDL-C and other lipid parameters. In addition, the G-allele carriers of variant rs599839 had a significant protective effect against the atherosclerosis.

Serum Leptin and Adiponectin Levels in Obese and Nonobese Asthmatic School Children in relation to Asthma Control.

There is growing evidence of a positive correlation between asthma and obesity in children and adults. Leptin and adiponectin regulate several metabolic and inflammatory functions. This study aims to evaluate serum leptin and adiponectin concentrations in asthmatic school children to investigate their association with obesity and the degree of asthma control. Obese asthmatic (OA) and nonobese asthmatic (NOA) children, aged 7 to 14, were randomly enrolled in this prospective study. Data on demographic, anthropometric, serum lipids, and spirometric measures and allergy status were collected and analyzed. Serum leptin was significantly higher (25.8 ± 11.1 versus 8.7 ± 11.1; P < 0.0001) and adiponectin levels were lower (2.5 ± 1.2 versus 5.4 ± 2.9; P < 0.0001) in OA compared to NOA children. The uncontrolled group had higher leptin and lower adiponectin levels compared to well and partially controlled asthma. BMI was positively correlated with leptin (r = 0.79; P < 0.001) and negatively with adiponectin (r = -0.73; P < 0.001). Mean BMI and leptin levels were observed to be higher in girls compared to boys. Stepwise multiple linear regression analysis showed that higher BMI and female gender had significant effect on serum leptin levels. Among asthmatic children higher serum leptin and lower adiponectin levels were significantly associated with obesity and showed no significant association with degree of asthma controls.

Quantitative metabolomic and lipidomic profiling reveals aberrant amino acid metabolism in type 2 diabetes.

Type 2 diabetes (T2DM) is a multi-factorial disease with a complex pathogenic mechanism; however a complete understanding of precise biochemical alterations accompanying the onset and progression of T2DM is lacking. Using a combination of untargeted and targeted metabolomic profiling approach we were able to delineate significantly altered metabolites in the diabetic (T2DM) group. Our results indicate significant perturbations in amino acid metabolism, TCA cycle and glycerol-phospholipid metabolism possibly impacting the overall glucose homeostasis in T2DM. A systems approach offers promise towards identification of clinically relevant markers of T2DM and novel molecular targets to foster drug discovery for effective therapeutic development for diabetes.