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Qatar Foundation Annual Research Conference Proceedings Volume 2018 Issue 2
- Conference date: 19-20 Mar 2018
- Location: Qatar National Convention Center (QNCC), Doha, Qatar
- Volume number: 2018
- Published: 15 March 2018
51 - 82 of 82 results
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The triple interaction DietMicrobiomeEpigenome: new approach to the noncommunicable diseases
Background/Objective: Qatar suffers the highest percentage of non-communicable diseases (NCD), such as diabetes and obesity among few countries in the world. There are two major components that could explain the NCD, which are diet and the genetic background. It's well demonstrated that diet affects the genome function in terms of epigenetic and microbiome modification. Recent scientific advancement or studies have shown that all these components could be the factors in defining the development of the NCD, but, there is no study that explains the direct connection of Diet-Microbiome-Epigenome. We want to explore the interaction of these three factors in a small pilot study on type 1 diabetes (T1D) creating a methodology that will be applicable for all NCDs and nutrition-related diseases. This study aims to identify specific nutrients that modulate gut microbiome; to define different microbiome composition and metabolites; and to define differential methylated regions (DMR) that is possibly affected by nutrients, gut microbiome and its metabolite. This abstract presents the study design and discusses methodologies that will be used in the study. Study design and methodology: We will compare 4 groups of subjects: T1D, T1D obese, pure obese, and lean controls. Pediatric patients will be recruited from Sidra OPC based on major inclusion criteria, (such as age should be between 6-12 yrs, no antibiotic treatment in the past 3 months, no chronic diseases except T1D and no history of cancer) and divided into four groups: (1) healthy lean children (5-84th percentile of BMI), (2) Obese ( ≥ 95th percentile of BMI;), (3) T1D and (4) Obese T1D. A comprehensive set of physical measurements (body weight, height and Waist circumference), clinical biomarkers for diabetes and obesity (mainly, blood glucose level, lipid and liver profile, HbA1c will be done with blood sample) and family history of diabetes, treatment history will be collected and most importantly dietary habits will be collected by 24 hrs food recall. Two sets of stool samples (one for microbiome analysis by 16S rDNA-sequencing; and one for fatty acids analysis by gas chromatography) and blood samples (one for DNA extraction for methylation analysis by Illumina DNA-methylation Array and one for RNA extraction for gene expression analysis using Fluidigm platform) will be collected from each subject. Data analysis will investigate any association of diet to the clinical phenotypes comparing the four groups of subjects, using logistic regression; two-sided P-value of < 0.05 will be considered statistically significant. Possible Research Outcomes/Conclusion: At the end of pilot study, we can able to define the (1) methodology workflow, (2) nutrients list or diet patterns that increase the risk of T1D in obese children, (3) specific microbiome pattern, in terms of composition and metabolite, in obese T1D children, and (4) specific nutrients and microbiome metabolites that alter DNA-methylation and gene expression in obese T1D children. This methodology workflow will be applied to other studies on NCD and nutrition-related diseases.
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Healthcare practitioners' views of their role in addressing the medical comorbidites of people with mental illness
More LessBackground: The lifespan of individuals with serious mental illness (SMI) is shorter compared to the general population. These disorders include schizophrenia, schizophrenia-like psychosis (e.g., schizoaffective disorder), major depressive disorder (MDD), and bipolar affective disorder (BPAD). This excess mortality is mainly due to physical illness and the lack of preventive medical care that is provided for this sector of the population. Although this has been explored Objectives: To investigate the prevalence rates of different physical illnesses in individuals with SMI in Qatar and to examine how these are being managed. Also, to explore health care practitioners' (HCPs) role, awareness and views on addressing the medical comorbidities of people with mental illness. Methodology: The published literature was explored by searching various electronic databases (PubMed®, Embace®, CINAHL®, PsychInfo®) on prevalence rates, morbidity and excess mortality rates in SMI. This was followed by a cross-sectional retrospective chart review of a cohort of patients with SMI attending the outpatient psychiatric clinic at Hamad Medical Corporation (HMC). A comprehensive electronic data extraction tool using SurveyMonkey® was used to collect patient demographics, psychiatric and medical co-morbidities, psychiatric and non-psychiatric medications, monitoring laboratory parameters and all relevant physical assessment findings such as blood pressure, weight and height. SPSS® was used for data analysis. The final phase consisted of semi-structured interviews with HCPs working in different health sectors (hospitals and primary health care centers). Thematic analysis was used to explore themes related to their views and perceived roles in addressing the medical comorbidities of people with mental illness. Results: The literature review yielded 792 relevant citations of which 17 met the inclusion criteria. Compared to the general population, metabolic, cardiovascular, respiratory, and musculoskeletal diseases were found to be more prevalent among severe mental illness patients from a global perspective. Of three hundred thirty six patients with SMI who were eligible for the retrospective chart review, almost a one third (29.2%) had at least one medical comorbidity documented. Diabetes was the most frequent, diagnosed in (16.1%) of these patients, followed by dyslipidemia (9.8%) and hypertension (9.2%). Monitoring of the risk factors associated with the comorbidities and other relevant physical assessment parameters (such as blood pressure, weight, HbA1c, blood glucose and lipids) were documented for less than 50% of patients, and some parameters, such as smoking status, were not documented at all. A total of eighteen face-to-face interviews with HCPS were conducted in the second phase of the study from which four major themes emerged, including 1) knowledge and awareness, 2) perceptions of current practices, 3) perceived barriers to care and 4) solutions to overcome these barriers. Conclusion: Results from the two exploratory phases of this study suggest that individuals with SMI in Qatar are less likely to receive standard levels of care for their medical comorbidities and less likely to be followed-up regularly. Poor documentation and lack of adherence to key practice guidelines for the provision of a holistic approach to care for individuals with mental illness may be contributing to fragmentation of care which will need to be addressed.
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Antidiabetic and Antioxydant Activities of Various Extracts From Different parts of Cleome Arabica Grown in Algeria
Authors: Fatiha Seglab, Yousfi Mohamed and Ihcen KhchebaBackground Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or relative lack of resistance to insulin. It is characterized by hyperglycemia and accompanied by various chronic vascular complications. One therapeutic approach for managing blood glucose-and thereby preventing or delaying the above-mentioned complications-is to decrease the catalytic activity of key enzymes involved in hydrolytic cleavage of dietary oligosaccharides such as α – amylase and α – glucosidase. Plants are used from antiquity as sources of medicament against various diseases. These properties are usually attributed to secondary metabolites which are the subject of a lot of research in this field. in particular phenolic compounds (class of naturally occurring pigments with ubiquitous distribution in plant Kingdom) which they display a remarkable biological properties [3]. Many plants are drug-design targets for the development of compounds for treatment of diabetes [1] Therefore, safer natural α - amylase inhibitors have been reported from plant sources [2] The Algerian flora, is one of the richest in the world, with its many species belonging to several botanical families of which a large percentage endemic, remains very little phytochemically as pharmacologically explored. In keeping with the general pattern of bringing one's contribution to the development of the vegetable reign as a source of natural bioactive substances we will be interested in the ethnobotanical and phytochemical study of some Algerian plants to discover a new therapeutics compounds, The expertise of our laboratory in natural substance from medicinal plants obtained by extractive phytochemistry reported the screening results for α - amylase inhibitory activity of more than 30 herbal extracts. This plant species were submitted to chemical screening, the analysis of the preceding biological targets led to the evaluation of the biological activity of the extracts of the specie Cleome arabica, to confirm and distinguish their antidiabetic activity by the inhibition of α-amylase.[4][2] A B S T R A C T The aim of this study consisted on the investigation of the antidiabetic and antioxidant activities of various extracts from Cleome Arabica collected on two seasons in the town of Laghouat in the steppe region of Algeria. The preliminary evaluation of the phytochemical composition of this extracts highlighted the presence of some chemical groups. This was confirmed by a quantitative analysis based on the determination of phenolic, flavonoid and condensed tannin content. The results of the effects of phenolic compounds on the kinetic catalyzed by the α – amylase using an in vitro model, to find a natural anti- diabetic compound from the plant indicate that the phenolic extracts from these plant have an inhibitory effect on the enzyme. The antioxidant activity test shows that our phenolic extracts exhibit good antioxidant capacity. Our study is the first report on potential inhibition of these plant extracts of digestive enzyme
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Harnessing Qatar Biobank to Understand Type 2 Diabetes in Adult Qataris
Authors: Ehsan Ullah, Raghvendra Mall and Halima BensmailObjectives: Chronic diseases such as diabetes, obesity and cancer are caused by the complex interaction between environmental factors (such as diet, lifestyle, and the built environment) and genetic factors. To understand the ultimate role of environmental, behavioral, and genetic factors along with their interactions, large-scale population cohorts have been established, mainly in Europe, North America, China, Japan, and Korea. The Qatar Biobank is a Qatar national population based prospective cohort study which includes the collection of biological samples, with long-term storage of data and samples for future research. The ultimate goal is to allow physicians and researchers to use the data collected from the biobank to conduct a large-scale study of the combined effects of genes, environment, and lifestyle on these diseases, to educate people on risk factors for these common diseases and to study disease incidence patterns and develop new diagnostic and therapeutic approaches. Using this pilot data, we had access to 60 features measured on 1000 Qatari citizen. To the best of our knowledge, this is the first study that has been done on Qatari biobank few months after its release. The main objective of the study is to identify the associated risk factors in Qatari population compared to those previously found in other parts of the world. Methods: In this study, we apply a panorama of state-of-the-art statistical methods and machine learning algorithms to investigate risk factors for diabetes. The statistical methods rely on lasso and group-lasso based techniques that can even use mixed continuous and categorical variables. The machine learning methods rely on tree-based models that provide importance of variables in predictions. In contrast to relying solely on the widely used baseline statistics, which perform marginal analysis considering a single variable at a time, these methods are based on multivariate analysis of the medical conditions. Moreover, we have applied survival and risk analysis on the prognosis of diabetes in the Qatari population. In our analysis, we used survival analysis to estimate the distribution of time of diabetes development. We have used Cox proportional hazards model to investigate the effect of different variables on the risk of diabetes. Results: Our study strongly confirms known risk factors associated with diabetes in Qatari population as previously found in other population studies in different parts of the world. For diabetes, biomarkers in Qatari population (as identified by different methods) include magnesium, calcium, HDL-C, chloride, insulin, c-peptide of insulin which have been previously reported by to list a few. Our study has revealed interactions of hypomagnesemia with HDL-C, triglycerides, and free thyroxine. These findings need further investigations. The survival analysis reveals that at the age of 40, there are 15% chances of developing diabetes in Qatari population and the chances increase to 50% at the age of 63. Qatari females are slightly at more risk to diabetes than males before the age of 40 but later on males have more chances to develop diabetes. The risk analysis reveals that calcium, magnesium, hemoglobin, triglycerides, and free-triiodothrymine play a very significant role in determining risk of the disease in Qatari population. Conclusion: Our study strongly confirms known risk factors associated with diabetes and obesity in Qatari population as previously found in other population studies in different parts of the world. Moreover, interactions of hypomagnesemia with other risk factors merit further investigations.
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Characterization of human microbiota of biological samples collected from healthy adult volunteers using different DNA extracting protocols
Introduction:The human body harbors bacteria, archaea, viruses, and eukaryotic microbes that inhabit interactive interfaces exposed to the external environment. This collection of microorganisms consists of about 100 trillion of microbes called the human microbiota and the total genes encoded by these microbes collectively called as human microbiome. They are strongly associated with the development of non-communicable diseases (NCDs) in addition to the role they play in communicable infectious diseases. Changes in microbiota has been reported in various NCDs including obesity, cancer, diabetes, metabolic syndrome, inflammatory bowel disease (IBD), asthma, cardiovascular disease (CVD), kidney disease (KD) and others. Advances in DNA sequencing and bioinformatics had enabled researchers the exploration of the genetic diversity of the uncultured component of host-associated microbial communities. The aim of this work is to test different DNA extracting protocols to characterize human microbiota of biological samples collected from adult volunteers. Materials & Methods: Biological samples such as human saliva, vaginal swabs and stool were collected from well-characterized adult participants. Total DNA were extracted from Vaginal swabs (n = 5) using DNeasy Blood & Tissue Kit and Mobio power Soil protocol; Stool samples (n = 17) using MoBio Power Fecal and Qiamp fast stool kits; Saliva samples (n = 8) using QIASymphony DNA Midi kit. DNA quantity and quality was assessed by Nanodrop spectrophotometer. Integrity of the DNA was reviewed on LabChip. Human microbiota diversities of different biological samples through different extraction protocols will be determined using MiSeq-Illumina high-throughput sequencing of bacterial 16S rDNA V1-V3 fingerprint. Sequenced data will be analyzed using QIIME pipeline. Results DNA measurement revealed that DNeasy Blood & Tissue Kit gave higher DNA yield with good integrity (2-8 ng/μL) than Mobio power Soil protocol (0.6-2 ng/μL) for Vaginal swabs. Likewise, MoBio Power Fecal kit (1.8-41.5 ng/mL) gave higher DNA yield than Qiamp fast stool kit (5-21 ng/mL) for stool samples. On the other hand, DNA Qiasymphony DSP kit gave (3-241 ng/μL) for saliva. Expected Outcome: From the previous studies by other groups, it is expected that Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria are the most abundant phyla in human microbiota. The abundance of the mentioned phylum may differ with respect to body sites. Actinobacteria members will be abundant on skin, Firmicutes and Bacteroidetes will be more abundant in gut. Firmicutes, Proteobacteria, and Bacteroidetes will be the more abundant in saliva and Firmicutes in Saliva. In addition, Each DNA extraction protocol has different strategies to lyse the human microbes. We speculate that the microbial diversity of same body site can be different with different protocols. Characterization of healthy human microbiome gives a better understanding of their role in human health during diseased conditions. Especially, Human gut microbiota influence the metabolism of host and it links to several metabolic disorders such as obesity, Type 2 diabetes and Metabolic syndrome when there is an imbalance in microbiota. Exploring Vaginal microbiome can guide as to find new therapeutic targets to treat several infections and to treat complications with preterm birth to pregnant women. This work will be a promising candidate to choose the adequate protocol based on the nature of the sample, which can guide us to explore the human microbiome in right path.
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1 25 Vitamin D3 levels in Qatari diabetes patients
Lina H.M Ahmed1, Youssra Dakroury1, Soha R. Dargham1, Aishah Latif2, Stephen Atkin1, Amal Robay1, Omar M. Chidiac1, Charbel Abi Khalil1 1 Weill Cornell Medicine Qatar, 2Antidoping Laboratory Qatar. Introduction: Vitamin D deficiency is a major issue worldwide and particularly in countries in the Middle East where full coverage of the body is a normal cultural practice. Epidemiology studies have suggested that vitamin D deficiency is associated with the development of diabetes where those levels are lower than normal subjects. However, the role of vitamin D in the development of diabetes complications is unclear. We hypothesized that vitamin D3 levels (25OHD3) and its active form 1,25 dihydroxyvitaminD3 (1,25OHD3) would differ between subjects with and without diabetes due to full coverage of the body being the determining factor. Methods: 499 Qatari subjects were recruited of whom 274 (54.9%) had type 2 diabetes and 222 (44.5%) did not. We used the Mann-Whitney test to compare the levels of both vitamin D outcomes, 25OHD3 and 1,25OHD3, their data were not normally distributed. First we compared the 25OHD3 and its active form 1,25OHD3 between diabetes and non diabetes subjects. Among those who were diabetic, we then correlated the 25OHD3 and 1,25OHD3 with diabetes complications (Table). 25OHD3 and 1,25OHD3 were measured by LC-MS/MS analysis. Results: Patients with diabetes were significantly more deficient in both 25OHD3 (p-value = 0.001) and 1,25OHD3 (p-value < 0.001) than non-diabetic patients. There were gender differences in the levels of vitamin D, with males observing less vitamin D levels than females (p-value < 0.001). Higher 25OHD3 levels were associated diabetic retinopathy (p-value = 0.014) but there was no difference in other parameters (Table). 1,25OHD3 deficiency was associated with hypertension (p-value = 0.043), but no other factors. Conclusion These data show that both 25OHD3 and 1,25OHD3 levels are lower in diabetes patients and in Qatari females, with only 1,25OHD3 deficiency being associated with hypertension, whilst both 25OHD3 and 1,25OHD3 deficiency were not associated with other complications of T2DM Table Alpha_D3, median (IQR) P-value 25OHD3, median (IQR) P-value Gender Gender Male (n = 97) 0.031 (0.037) 0.009 Male (n = 121) 8.26 (11.01) 0.000 Female (n = 96) 0.022 (0.032) Female (n = 153) 4.53 (7.44) Hypertension Hypertension No (n = 76) 0.033 (0.031) 0.043 No (n = 100) 6.39 (10.39) 0.612 Yes (n = 117) 0.023 (0.033) Yes (n = 174) 6.06 (10.61) Dyslipidemia Dyslipidemia No (n = 61) 0.032 (0.036) 0.166 No (n = 75) 6.86 (10.63) 0.061 Yes (n = 132) 0.024 (0.032) Yes (n = 199) 5.56 (9.00) Diab Retinopathy Diab Retinopathy No (n = 127) 0.029 (0.032) 0.196 No (n = 192) 6.25 (8.96) 0.014 Yes (n = 66) 0.022 (0.031) Yes (n = 82) 7.98 (11.76) Diab Neuropathy Diab Neuropathy No (n = 159) 0.028 (0.032) 0.613 No (n = 223) 6.25 (10.66) 0.740 Yes (n = 34) 0.023 (0.034) Yes (n = 51) 6.18 (7.79) Peripheral Artery Disease Peripheral Artery Disease No (n = 183) 0.027 (0.032) 0.222 No (n = 262) 6.14 (10.53) 0.287 Yes (N = 10) 0.035 (0.037) Yes (N = 12) 10.78 (12.66) Coronary Artery Disease Coronary Artery Disease No (N = 161) 0.029 (0.034) 0.058 No (N = 234) 6.31 (10.62) 0.871 Yes (N = 32) 0.021 (0.023) Yes (N = 40) 5.49 (8.74) Stroke Stroke No (n = 186) 0.027 (0.032) 0.669 No (n = 262) 6.27 (10.62) 0.369 Yes (n = 7) 0.023 (0.021) Yes (n = 12) 4.92 (9.56)
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Prevalence of type 2 diabetes in Qatari women aged between 18 to 40 from Qatar Biobank
Authors: Abeer Elshewehy and Soha DarghamPrevalence of type 2 diabetes in Qatari women aged between 18 to 40 from Qatar Biobank. 1Abeer Elshewehy, 1Soha Dargham, 2Eric Kilpatrick, 1Lina Ahmed, 1Youssra Dakroury, 1Stephen L Atkin 1Weill Cornell Medicine- Qatar, 2 Sidra Medical and Research Center Background: The Qatar STEPwise surveillance reported that the prevalence of type 2 diabetes amongst Qatar nationals was 16.7% in 2012. This high prevalence of diabetes will translate into significant morbidity and mortality through diabetes complications. Methods: Qatar Biobank extracted data from all women between 18 to 40 years (inclusive), 749 women in total. Women with (Group A: HbA1c ≥ 6.5%; n = 12/708; 1.7%) and without (Group B; HbA1c ≤ 5.6%; 608/708; 85.9%) type 2 diabetes were identified and their demographic details compared. Prediabetes was found in 88/708 women (HbA1c 5.6-6.4%; 11.7%). Biostatistical analysis was undertaken using SPSS. Results: Group A (HbA1c ≥ 6.5%) had worse Framingham Risk Score (2%) than Group B (HbA1c ≤ 5.6 %) ( < 1%). All results are reported as mean value Group A versus Group B. Conclusion: In this small young cohort, 1.7% of women had a WHO diagnosis of type 2 diabetes and 11.7% with prediabtes. Diabetes is perceived to be a disease of the middle aged and older individuals, but this study shows that there is a need for early screening and intervention for the prevention of type 2 diabetes in young Qatari women below the age of 40. Limitation of the study: Small number of participants and that latent type 1 diabetes could not be excluded that may have affected the overall prevalence, though this was expected to have a minimal impact. Acknowledgments: We are grateful to the Qatar Foundation and the Qatar Biobank for their support and assistance, and for Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine in Qatar
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Tracking health awareness in MENA through Facebook Advertising audience estimates
Diabetes epidemic is claiming more lives than ever, with the number of people with diabetes rising from 108 million in 1980 to 422 million in 2014. World Health Organization estimates that in 2015, diabetes was the direct cause of 1.6 million deaths and in 2012 high blood glucose was the cause of another 2.2 million deaths (http://www.who.int/mediacentre/factsheets/fs312/en/). The obesity and diabetes are especially prevalent in GCC, and Qatar in particular where 70% of the population either overweight or obese (http://www.qatar-tribune.com/news-details/id/54297). The most common form of diabetes – Type II – is caused by a combination of lifestyle factors and genes, thus numerous campaigns are underway to encourage change in daily behaviors which may lead to obesity and diabetes. Recently, Facebook and other social media has become a platform for patient interaction, outreach and education.The scale and reach of Facebook and other social media provide a unique opportunity to track the awareness and interest in health-related topics of large slices of population. This is imperative, as the awareness of an issue is the first step to lifestyle behavior change. In this work, we use the Facebook Advertising platform to track the interests of millions of people across the MENA regions on health-related topics. In particular, before ordering an advertising campaign, the potential advertiser is free to query Facebook about the potential reach, or estimated audience, of a particular selection of location, gender, age, language, interests, and a variety of other attributes. For example, when we select Arabic-speaking women living in Qatar between the ages of 30 and 50 who are interested in dieting, Facebook gives an estimated audience of 4,300 users who would see our hypothetical ad. As such reach estimates do not divulge information on any particular user, this information provides a window into otherwise private behaviors of Facebook users, in aggregate. In the present study, we examine the interest Facebook users from the countries in the MENA region have concerning health-related topics such as Obesity and Diabetes awareness, as well as general Fitness and Wellness and Healthcare. These interests are then compared to baselines such as Luxury Goods and Shopping, as well as health-related ones like Fast Food. We designed a visual analytic interface to enable exploration of these health awareness data. Once the interests are selected (Fig. 1, top), demographic slices of the data are presented in tree maps (Fig. 1, left) and on a choropleth map (Fig. 1, right), with each segment colored with a Health Awareness Score. The user can select a particular demographic (such as male gender) or country, automatically updating all other demographic segments to correspond with the current selection.Fig. 1. Comparison of interest in Physical Activity vs Fast Food for young women who are local to each of the MENA countries. Tool is available online at http://sha.qcri.org/ Using Facebook Advertising, or any other social media, as a source for health awareness monitoring has several drawbacks, the most prominent of which is the biased sampling of the population. However, with the continued adaptation of these platforms across the world and segments of population, they become increasingly representative of the general population. This can be mediated by careful cross-correlation with authoritative data sources such as statistics provided by the World Health Organization. Another drawback comes from the black box nature of the platform, as we are not purview to the internal processing and definitions the platforms use to come up with the metrics they reveal. Our ongoing efforts are addressing this by comparing the metrics provided by Facebook to the known disease prevalence as collected. In particular, if we look at the rates of diabetes (as published by the Institute for Health Metrics and Evaluation (IHME) (http://www.healthdata.org/), we can compare them to the estimates of interest Facebook provides. In Qatar, the Pearson correlation between diabetes rates and Facebook awareness of Diabetes Mellitus Type II across different age groups is r = 0.963 (p < 0.001), suggesting the awareness of disease rises as the incidence of the disease increases in the population. Interestingly, the trend reverses when we correlate interest in Diabetes Mellitus Type I (a much rarer form of disease, usually diagnosed in children) at r = –0.844 (p < 0.002), indicating the focus of the population remains with the Type II. In summary, this demographically rich data source has a great potential for improving awareness campaign tracking and dynamic opinion monitoring. Our study develops new methodologies and tools to collect, verify, visualize, and make this data available to the policy makers, campaign organizers, and many other potential actors interested in monitoring public opinion.
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Vascular endothelial dysfunction as the mechanism for the development of obesity
Authors: Nasrin Mesaeli, Rajaa Saleh Dalloul, Tatiana Lobo and Hamid MassaeliVascular endothelial dysfunction as the mechanism for the development of obesity Raja'a Dalloul, Tatiana Lobo, Hamid Massaeli, Nasrin Mesaeli Weill Cornell Medicine- Qatar, Qatar Foundation, Doha, Qatar Background: Obesity is one of the major public health issues in the world with a rapid increase in its prevalence. According to the last public health report from supreme public health in Qatar in 2012, 71.8 % of the women were overweight compared to 68.3% of men. Among the gulf region, Qatar has the 6th highest rate of obesity in young boys. Moreover, the WHO survey in 2009 showed 70% of the Qatari children were obese because of the nutritional changes and unhealthy lifestyle. Adipocytes are considered the only cells where their size can vary in physiological conditions. Adipose tissues grow as they store excess energy intake. It's well established that adipose tissue is highly vascularized. These vascular networks play a vital role in the adipogenesis process. The vasculature of adipose tissue provide oxygen, growth factors, nutrients, and cytokines to the progenitor cells that are differentiated into pre-adipocytes and vascular endothelial cells. Vascular endothelial cells form the inner barrier of the vessel and is responsible for maintaining the vascular vasodilation and constriction. Defect in the endothelial cell function has been shown to result as a consequence of different diseases such as obesity, diabetes and high blood pressure. An increase or decrease in the generation of the reactive oxygen is one of the main cause of endothelium dysfunction. The fluctuation in the balance of these factors in the endothelial has an influence in the adipocyte cells which is responsible for the formation of fats or fatty tissues which cause an impairment of adipocytes and may lead to obesity. Calreticulin (CRT) is a multifunctional protein that is expressed in the endoplasmic reticulum of all mammalian cells. The main functions of CRT are regulation of intracellular Ca2+ hemostasis and lectin like chaperone. As part of ongoing research in our lab, we have developed a mouse model overexpressing CRT in endothelial cells. One of the phenotypes of this mouse is the development of obesity and type II diabetes overtime. Therefore, the current research was to examine the hypothesis that endothelial specific overexpression of CRT in mice leads to endothelial dysfunction leading to obesity and diabetes. Methodology: A cell targeted transgenic mouse model overexpressing CRT in endothelial cells [will be referred to as (ECCRT+)] was developed in our lab and used in our study. One of the major phenotype of these mice is the development of visceral obesity and diabetes. To characterize these mice phenotype, 4 weeks old wild-type (wt) and transgenic (ECCRT+) litter mate mice were fed with special diet containing either high fat (60%) or low fat (10%) diet for different time points (8-24 weeks). Body weight and blood glucose was measured bi-weekly. At the end time point glucose tolerance test (GTT) was performed to determine the state of diabetes. Epididymal adipose tissues were collected from the wt and ECCRT+ mice. The tissues were embedded in paraffin, sectioned and stained using histological and immunohistochemical techniques to examine the phenotypic changes (shape and size) of adipocyte in ECCRT+ and wildtype mice. Results: Our results illustrated that these mice suffered from endothelial dysfunction. The GTT assay illustrated that ECCRT+ mice developed diabetes at 16 weeks of age when on regular diet (10% fat diet) and high fat diet expedited the development of diabetes. Fat to body weight ratios, and histological analysis of the fat from these wt and ECCRT+ mice showed significant changes in the fat volume, adipocyte size and adipocyte number suggesting a possible association between endothelial dysfunction and adipogenesis which correlate to the obesity and diabetic developed in these mice. Conclusion: Many studies have focused on how obesity induces endothelial dysfunction. Our study is the first to show an important role of endothelial dysfunction in the process of adipogenesis leading to the development of obesity and diabetes. Our data also highlights the importance of an endoplasmic reticulum chaperone in this process. Acknowledge: This project has been funded by NPRP07-208-3-046.
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Retinal blood vessel analysis using IFLEXIS software on fundus images from the Qatar Biobank
Authors: Arnout Standaert, Patrick De Boever, Bart Elen and Rayaz MalikRetinal examination is a diagnostic pillar in ophthalmology for the early detection of eye diseases such as retinopathy (hemorrhage/exudate) and glaucoma (optic disc abnormality). Large population-based studies have shown that retinal vessel morphological quantification may be useful in predicting the development and progression of hypertension, diabetes and cardiovascular diseases (CVD). The rationale for this is that the retinal microcirculatory bed shares similar anatomical and physiological characteristics with the coronary and cerebrovascular circulations. Therefore, quantification of retinal vessel metrics may reveal insights into the development of coronary artery and cerebrovascular disease. Indeed, retinal blood vessel analysis has gained increasing interest in recent years for predicting the development of hypertension, coronary heart disease, stroke and type II diabetes. A number of software algorithms have been used to quantify retinal vessel morphology, but they require manual input and are time- and labor-intensive. Fully automated image analysis allows objective and accurate assessment of retinal vessel parameters. VITO has developed and released IFLEXIS, software for semi-automated retinal vessel analysis, which includes algorithms to determine blood vessel widths, vessel branching and vessel network complexity, integrated in a user-friendly workflow. During the Belgian Economic Mission to Qatar in March 2015, WCM-Q, VITO and Qatar Biobank signed a Memorandum of Understanding to explore the potential of retinal analysis for the early detection of retinal vessel abnormalities in subjects attending the QBB. Fundus images from 774 people attending the Qatar Biobank contained images from healthy controls, subjects with Impaired Glucose Tolerance (IGT), Hypertension (HT) and/or Type 2 diabetes (T2DM). Here, we report the utility of IFLEXIS in a subset of 597 fundus images obtained from 574 persons which could be analyzed. The following parameters were quantified: (i) FD (fractal dimension, using the box counting method), FFD (Fourier fractal dimension) and lacunarity of the vessel network, and (ii) CRAE, CRVE (central artery/ vein equivalent) and AVR (artery-to-vein ratio). Analysis revealed the following mean (range) for this population: 1.39 (1.32 – 1.53) for FD, 2.75 (1.77 – 2.98) for FFD, 1.00 (0.94 – 1.08) for lacunarity, 154.73 (93.79 – 195.67) for CRAE, 233.26 (159.67 – 307.94) for CRVE and 0.67 (0.48 – 0.93) for AVR. Statistical tests for the retinal parameters reveal interesting differences between the studied disease groups. When comparing HT with control subjects, statistically significant differences were found for the CRAE (150.05 ± 2.17 versus 157.88 ± 1.91, p=1.02×10-6) and the CRVE (231.74 ± 3.60 versus 238.28 ± 2.83, p=0.031). Comparing subjects with HT and T2DM with controls also revealed significant differences in CRAE (145.15 ± 3.62 versus 157.88 ± 1.91, p=4.66×10-8) and CRVE (218.47 ± 5.16 versus 238.28 ± 2.83, p=3.31×10-9). This study showed the feasibility of retinal vessel analysis of standard fundus images from the QBB using IFLEXIS. Despite the fact that the fundus images were originally not taken for this purpose, IFLEXIS software can extract novel retinal blood vessel dimensions. As blood vessel analysis has been shown to be relevant for chronic disease prediction, we propose to utilize the baseline assessment to augment the Qatar Biobank database to predict incident disease in follow-up studies. Single retinal features already appear to differentiate subjects with hypertension and/or diabetes compared to controls. We will undertake quantification of a larger image data set and will perform further data analysis to refine both the diagnostic and/or prognostic use of retinal metric analysis in the QBB population. To this end, we will combine retinal vessel metrics with demographics such as age, duration of disease and other metabolic parameters and study the association with whole genome sequence patterns in this population.
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Cerebral blood flow and autoregulation in acute TIA patients from a general hospital in Qatar
BACKGROUND The Arabian Gulf region is rapidly developing, with major changes in lifestyle that can increase the risk of cardiovascular diseases, including TIA and stroke. Stroke constitutes a major cause of morbidity and mortality in Qatar. Cerebral auto-regulation is an intrinsic protective mechanism guaranteeinghemodynamic integrity of cerebral circulation. It modulates cerebral blood flow(CBF) in order to meet regional perfusion demands despite variations in arterial blood pressure. Impaired cerebral auto-regulation is associated with poor functional and prognostic outcomes in patients with ischemic stroke. OBJECTIVES The study has two arms; one arm is a health improvement project conducted in Qatar with the aim of developing, establishing and maintaining an acute stroke database (registry) in Qatar. The second arm is an applied research project with the aim to correlate CBF and cerebral auto-regulation and microalbuminuria in TIA patients, and to assess the prognostic significance of such a correlation. Thus far, no physiologic or biochemical biomarker has been proven as an effective predictor of poor outcome in TIA patients. DESIGN / METHODS Fifty-six patients (35 men, mean age, 53.2 yrs) with acute TIAs or small strokes (TIAs with tissue evidence of infarction) were enrolled last year and evaluated with bilateral, simultaneous TCD studies of their MCAs CBF within 72 hrs of the indexed event. On best medical therapy, the patients were followed up at one year for outcomes measures of death, stroke and recurrent TIAs in an attempt to correlate them with the TCD parameters. RESULTS Fifteen healthy volunteers (mean age 30 years) were studied using voluntary breath-holding technique to provide the hypercapnia stimulus to effect cerebral auto regulation of CBF in their MCAs. Fifty TIA patients (mean age 53.7 yrs) had complete TCD studies and 48 were followed up to one year. Seven experienced symptoms or signs of a new cerebrovascular event (3 strokes and 3 recurrent TIAs) for an annual rate for cerebrovascular events of 14%. The average BHI for the respective groups were 0.9 ± 0.78 for the controls, 0.62 ± 1.1 for the TIA patients and 0.31 ± 0.85 for those who had cerebrovascular events on follow up. MCA TCD studies with BHIs in the TIA patient group with stroke or recurrent TIA at follow up showed a tendency towards abnormality as compared to healthy controls (p>0.05) CONCLUSION Preliminary results indicate the feasibility of TCD and BHI in acute evaluation of TIA patients for the purpose of prognosis and functional outcome. Further studies are necessary to confirm their clinical value. Calculating BHI has potential of a strong prognostic predictor of future cerebrovascular events. It could be used as an inexpensive non-invasive tool for the acute evaluation of TIA patients. Together with other neuroimaging studies it brings a real time neurophysiologic dimension to the assessment and possible prevention of stroke.
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Smart wearable sensing platform with wireless communication and embedded processing for health monitoring applications
Authors: Younss AitMou, Menatollah Elgendy, Safiya Jan, Augusto Manuel Lucas, Almiqdad Elzein and Amine BermakDiabetic patients tend to develop plantar ulcers due to various factors related to their pathology. These factors include, but are not limited to, a lack of plantar sensation, a poor blood circulation, and feet deformities. The plantar ulcers can be managed and cured if detected at an early stage and appropriately treated. However, if not detected early, they can evolve to rich critical stages involving extreme curative strategies such as amputation. Accordingly, it is crucial to detect these ulcers at an early stage. A common strategy to prevent ulcers worsening is by increasing the patient's medical check frequency. Although beneficial, this therapeutic approach is time consuming and might not be a perfect solution for elderly patients, and patients with reduced locomotive abilities. Accordingly, various groups have oriented their work toward the development of smart shoes to monitor plantar physical parameters under various conditions [1-3]. Previous studies have focused on healthy foot pressure analysis and soft therapies. Moreover, none of these studies has developed a centralized data system. Accordingly, our present work aim to develop a user and mobile phone friendly wireless device that is specifically targeting patients with diabetes to prevent plantar ulcers from reaching the critical levels by early detection of peak pressure, temperature, and humidity. Moreover, to improve patient monitoring, collected data will be centralized in a global database. To the aim of our present work we employed Velostat (a.k.a. Linqstat) to acquire plantar pressure. Velostat is thin conductive material that was previously employed as pressure sensor. When combined with an array of conductive net, this material can act as an array of pressure-sensors. Accordingly, we built a 10 cell array to acquire pressure from 10 strategic plantar locations, namely: Medial Plantar; Lateral Plantar; Saphenous; Sural; Tibial. Plantar wounds are often associated with increased local temperature that reflects a local sub-dermal infection. To monitor the temperature alteration, we utilized a DHT11 module. The DHT11, is an ideal module for simultaneous measurement of both temperature and humidity. Wound infection is often accompanied by local swelling and bleeding, Hence, the humidity detection. To acquire and pre-process the raw data, we employed an ATMEL 8-bit Microcontroller (ATMEGA 2560). Given it's high pin count, this device allowed as to overcome adding multiplexers to handle the significant number of input signals (13). Thus, allowing us to reduce the prototype footprint. To secure an effective data transfer to the mobile phone, we have used an HC-06 as a Bluetooth transceiver. Once collected and sampled (1 Hz rate), the data is then transferred to the mobile phone trough the Bluetooth connection. For user convenience, the mobile application displays current values at 1 Hz frequency along with a time-stamp chart. When the temperature reaches a critical wound level (33-34°C)[4], the device sends a warning notification to the monitoring application that is held by the health-care processionals (i.e. nurses and doctors). In addition, wound maceration[5] and drying[6] notification warnings are detected and sent to the monitoring application. The later values are calculated based on the humidity sensor's raw data. The monitoring application pulls data from the server and evaluates the wound severity by combings all sensors' data. To centralize all collected data, and improve patient monitoring, the raw and analyzed data are stored in a global database that can be accessed from either a web application or the monitoring mobile phone application. Reference: 1. Bamberg, S.J.M., Benbasat A.Y., Scarborough D.M., Krebs D.E. Paradiso J.A. Gait Analysis Using a Shoe-Integrated Wireless Sensor System. IEEE Transactions on Information Technology in Biomedicine, Vol. 12, No. 4, July 2008, pp. 413-423.2. Paradiso, J.A., Morris, S.J., Benbasat, A.Y., Asmussen, E., «Interactive Therapy with Instrumented Footwear,» in the Proc. of the ACM Conference on Human Factors and Computing Systems (CHI 2004), Extended Abstracts, Vienna, Austria, April 27-29, 2004, pp. 1341-1343.3. Benbasat, A.Y., Morris, S.J, and Paradiso, J.A. «A Wireless Modular Sensor Architecture and its Application in On-Shoe Gait Analysis.» In the Proceedings of the 2003 IEEE International Conference on Sensors, October 21-24, Toronto, Ontario, pp. 1086-1091.4. Dini V, Salvo P, Janowska A, Di Francesco F, Barbini A, Romanelli M. Correlation Between Wound Temperature Obtained With an Infrared Camera and Clinical Wound Bed Score in Venous Leg Ulcers. Wounds 2015, Oct 15.5. K.F. Cutting, R.J. White. Maceration of the skin and wound bed. 1: Its nature and causes. J Wound Care, 11 (2002), pp. 275-278.6. G.D. Winter. Formation of the scab and the rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature, 193 (1962), pp. 293-294
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Feasibility study of the use of mobile health for diabetes management in Qatar poster
Noor Suleiman1, Dabia Al Mohannadi1, Majed Lababidi2, Abdulla Al Misnad2, Mohammed Bashir1, Luis Luque3, Abdul Badi Abou-Samra1 Keywords: diabetes, mobile technology, internet, eHealth, smartphone, chronic condition Diabetes Mellitus (DM) is a chronic disease characterized by an elevated level of blood glucose and carries the risk of acute and chronic complications resulting in significant healthcare burden. DM has a high prevalence across many nations especially within the Middle East. In Qatar, DM prevalence in the adult population is approximately 16.7%. DM management is a well-known complex process that requires both lifestyle changes and effective pharmacologic treatment plans. To avoid DM complications, effective behavioral change, extensive education and promotion of appropriate self-management are key. Self-management tools are developing fast. Data recording of blood glucose and lifestyle changes have progressed from writing them on paper, to uploading them to computers, to recording them on mobile phones using traditional phone functions, and finally to using smartphone apps. Mobile health is becoming one of the fastest growing areas of effective healthcare delivery in many countries with health education and awareness programs being increasingly recognized as the key players. The surge of mobile healthcare (m-Health) in the last few years is due to the massive demand of such systems to alleviate and provide more efficient and effective healthcare delivery mechanisms especially for chronic disease management and self-care. Diabetes mobile technology is an emerging and rapidly expanding field that seeks to combine cutting edge behavioral insights with best practice in diabetes self-management education to improve patient empowerment and deliver better patient outcomes. However, there is a lack of research on the use of mobile technology to support diabetes self-management in the Arab world. The question that arises is whether or not, diabetes mobile applications are effective in improving glycemic control, clinical outcomes, quality of life and overall patient satisfaction, in diabetic patients in Qatar. We have the hypothesis that with utilization of the mobile application, patients will have improved diabetes knowledge, patient satisfaction and empowerment; glycemic control and diabetes outcomes; together with improved patient-educator/doctor interaction Qualitative research methods such as focus groups and interviews have been conducted among dozens of patients and health care professionals to identify strategies to design a patient-centered mobile application for diabetes, named droobi health. The main purpose of this application is to enhance patient care and improve clinical outcomes of diabetic patients through an active engagement with patients. Patients will have access to tools to monitor, manage and control their diabetes, enabling communication between patients and care providers while providing access to up-to-date diabetes educational materials. droobi health will provide a single source of patient self-management and lifestyle information for better collaboration between patient and care providers to positively interact and engage with the patient and personalize educational material when it is required. This app has the home-advantage of being created in Qatar for our particular patient population, taking into account the cultural adaptation and context, which is missing in the existing apps. We have completed the design based on feedback from healthcare providers and patients. Droobi provides a platform where the patient and his or her clinical care team can interact in order to address the patient's concerns in a timely manner. Additionally, Droobi aims to empower the patient towards implementing self-management together with providing robust education and training for the patients towards their disease resulting in increased knowledge and awareness. The feasibility of Droobi will be conducted in a small pilot, with its effectiveness later examined in a clinical trial. Hamad Medical Corporation Trio InvestmentsQatar Computing Research Institute
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Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4hydroxynonenal in obese diabetic patients
Authors: Shamma Abdulla Almuraikhy, Mohamed Elrayess and Wael KafienahOBJECTIVE: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. METHODS: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. RESULTS: Preadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. CONCLUSION: This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.
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A high carbohydrate diet increased adiposity and compromised vasodilation in rats
Authors: Hamda Aboujassoum, Nelson Orie, Lucie Clapp, Hamda Al-Naemi and Video Mohamed AliIntroduction Obesity is an epidemic problem that impairs human health. It can be defined as the accumulation of excessive body fat mass, leading to abnormal changes. The world is witness an explosion in the number of obesity cases. Worldwide obesity prevalence has more than doubled since 1980s as reported by World Health Organization (WHO). Indeed, the American Medical Association announced that obesity should be classified as a chronic disease. Qatar ranks sixth globally in the prevalence of obesity according to the International Association for the Study of Obesity. There are several causes considered to contribute in the development of obesity such as: genetics, health, diet and lifestyle. However, access to high energy-dense food, and physical inactivity makes a significant contribution to the increasing rate of obesity. Increasing body weight is closely associated with cardiovascular morbidity and mortality. It has a total impact on cardiovascular disease (CVDs) in the general population approximately equal to that of smoking. The relationship and the exact role by which obesity induces the cardiovascular risk are poorly investigated. This study aims to establish a diet-induced obesity rat model and to investigate the cardiovascular diseases risk factors associated with obesity. It also aimed to examine the effect of dietary weight loss on the reversibility of these risk factors. Methodology Male Sprague Dawly (SD) rats 8-9 weeks age old, were grouped into three categories: NC group fed with Normal chow (NC) and had access to regular water ad libitum, CAF group fed with a combination of cafeteria style diet (CAF) and normal chow with 5% sugar water ad libitum for 15 weeks, and reversibility group fed with CAF diet and NC ad libitum to induced weight gain and then switched to NC only for four weeks. The nutritional contents for each diet was: NC (49% CHO, 14.37% protein, 4.65% fat) and CAF (60-70% CHO, 9-12% protein, 10% fat). Body weight, food and water intake were measured weekly throughout the study. Blood was collected to test the changes in the metabolic parameters. Large vessels responsiveness was examined by using organ bath, in response to noradrenaline (NA) and acetylcholine (Ach). Results Results showed that CAF diet has an effect on body weight. All CAF fed-rats gained weight significantly with higher consumption of CAF diet compared to NC. A significant change in their lipid profile was also observed; it showed a significant increase in triglycerides and a decrease in HDL levels. In the reversible group, rats showed a slight weight loss of approximately 6% in 4 weeks. This weight loss was associated with a more favorable lipid profile; triglycerides and HDL returned to normal levels when CAF diet stopped. The vascular studies data suggests noradrenergic contractions in the CAF-fed group were muted compared with the control (NC-fed group). Similar effect was observed in the reversibility, when CAF diet stopped for 4 weeks. The Ach relaxation pattern suggests CAF feeding was associated with endothelial dysfunction. This effect was not reversed when the diet changed to normal chow. Conclusion In conclusion, this study developed a diet-induced obesity rat model with metabolic changes associated with obesity. It specifically examined the vascular changes caused by dietary weight gain and loss. Further investigations are in progress in order to investigate the mechanisms underlying these changes.
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Prioritizing Access to the National Diabetes Center NDC Services Based on Clinical Need
Authors: Raissa Jacinto Puddao, Sara Darwish, Mariam Al-Malaheem and Mahmoud ZirieNDC is one of the busiest services at Hamad General Hospital (HGH) with 450-1000 new referrals monthly and an average waiting time of 84 days for an initial appointment. Triage guidelines from several government institutions in Canada, UK, and Australia stated that the patients with urgent conditions should be assessed within 2 weeks. Delaying urgent cases management poses a great patient safety risk that may endanger patient health and can lead to increased healthcare cost. In December 2016, a multidisciplinary team (physician, nurses, administration, and quality staff) was formed to pilot an urgent clinic service. The team standardized triaging criteria, calculated waste, and improved the process from triaging until the first appointment at NDC. Goal: To provide timely diagnosis and management for newly-referred patients to NDC who are considered urgent after physician's triage. Team Aim: To improve the percentage of referred patients with urgent cases who attended their initial consultation visit at the Diabetes-Endocrine Urgent Clinic within 2 weeks from physician's triage to 60% by May 2017. Methods: An urgent clinic exclusively for indicated urgent new referrals was piloted last December 2016. Fishbone diagram and process map were created. For testing changes, the Model for Improvement or Plan-Do-Study-Act (PDSA) was utilized. Several trials were done to identify the cases to be considered urgent during triage, manpower, clinic scheduling, appointment booking process, feedback gathering, and data collection. Results:For the past 9 months, there were 769 patients triaged to the urgent clinic. Around 65% of them were seen within 2 weeks, 12% no-show, and 23% were unable to attend due to various causes. We were able to surpass our goal for several months starting from January 2017 with the exemption in June 2017 when the clinic was closed for 10 days due to the Eid holidays.
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Intermittent fasting during Ramadan causes transient loss of body fat and improvement in insulin sensitivity
Background. periods of voluntary abstinence from food, such as intermittent fasting, has been practiced since earliest antiquity by people around the globe. The benefits of restricting energy intake severely for two days a week while eating normally the rest of week has been popularised. However, the evidence for the health benefits of fasting in humans is often extrapolated from animal studies, based on observational data on religious fasting, or derived from experimental studies. Furthermore, periods of prolonged daily fasting may be especially beneficial to improving sensitivity to insulin. However, whether the reduced water consumption and physical activity during ramadan may mitigate these health is less well studied. Therefore, This study tested the hypothesis that prolonged daily fasting, for greater than 12 h in a 24 h cycle, without calorie restriction, reduces hyperinsulinaemia even in the absence of weight loss.Methods. All participants were non-Caucasians males. The study consisted of three phases: phase1:2 visit in the 10 days prior to the start of ramadan, phase 2:3 visits (1 per week) during the 30 days of ramadan and phase 3:1 vist one month after ramadan, when normal patterns of eating and exercising had been resumed. At each study day subjects attended twice, once in the morning (between 08:30 and 10 AM) and once in the afternoon (between 2.00 to 4.30 PM). All subjects completed a questionnair detailing age, smoking habits, medical history, sleeping patterns, dietary intake and training schedule. The studies were approved by National research Ethics Committee and written informed consent was obtained for all participants. 10 subjects completed the study.Weight (Kg) and body composition was measured by electrical bio-impedance (Tanita MC-980 MA) with light cloths at each AM visit. Height (m) was measured on the first visit and BMI was calculated by using formula body weight (kilometres) divided by height (meters) squared. All the participants remained seated for 10 minutes prior to determination of systolic and diastolic blood pressure, and heart rate using an automatic digital blood pressure monitor from the non-dominate arm and mean atrial BP (MAP). blood samples were drawn at all occasions through the ante cubical vein into tubes containing no anti-coagulant or EDTA, separated and stored until analysis. Plasma glucose (mmol/L), serum triglycerides (mmol/L), high density lipoprotein cholestrol (mmol/L), total and direct bilirubin (umol/L), Alanine transaminase (U/L), Aspartate aminotransferase (U/L), urea (mmol/L), uric acid (umol/L), and creatinine (umol/L) concentrations were determined on a chemistry analyser. Insulin (mU/L) concentrations were determined by ELISA. Results are experssed as mean and standard deviattion for normally distributed data and median and iterquartile ranges for skewed data. Significance was defined as P < 0.05.Results. There was significant reduction in body weight during the 2nd and 3rd weeks of ramadan. This weight loss was not sustained in the period immediately following the fasting months as all weight loss was regaind. Body mass index followed the same pattern as body weight. Body fat, both % and mass, decreased soon after the start of fasting (within 2 - 3 days) and was sustaind through the three ramadan testing phases. However, like body weight this loss in body fat was regained in the period immediately after normal eating patterns were resumed.There were no significant changes in muscle mass or body water as a consequence of fasting during Ramadan.There were no significant changes in blood pressure, pulse or basal metabolice rate throughout the entire study.Please (see Table 1) for details.Of note is that all participants were hyperinsulinaemic through the periods of testing prior to and after the cessation of the fasting month. However, during the fasting period insulin levels were significatly reduced. Similar trends were also apparent for alanine transaminase and triglycerides (see Table 2). No changes were seen for all other measured variables. All subjects remained euglycaemic and normotentive.Conclusions. This study shows, for the first time that, prolonged periods of fasting during the day, even without reducing overall daily calorie intake, favours loss of body fat, while preserving muscle mass. This was accompanied by significant improvement in systemic hyperinsulinaemia and indices of liver function.
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Corneal Confocal Microscopy Detects Alterations in Corneal Endothelial Cell Morphology in Patients Admitted with Acute Ischemic Stroke
By Adnan KhanBackground The major risk factors for stroke include diabetes, hypertension, smoking, dyslipidemia 1 and metabolic syndrome 2. Endothelial dysfunction is central to promoting vasoconstriction and thrombosis and limited angiogenesis 3 and may also contribute to enhanced plaque vulnerability, triggering plaque rupture, and thrombus formation. There are many methods to assess endothelial dysfunction including brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine and alterations in endothelium dependent dilatation using laser Doppler. We have previously shown significant abnormalities in gluteal resistance vessel endothelium dependent dilatation in patients with obesity 4, diabetes and hypertension 5. Patients admitted with an acute ischemic stroke had reduced forearm flow mediated dilatation and increased circulating levels of P-selectin, a marker of endothelial dysfunction, suggesting widespread vascular abnormalities 6. These measures of endothelial dysfunction are evaluated in vascular territory which is a distance from the brain. Direct imaging of the cerebral blood vessels can identify atherosclerosis 7 and Magnetic resonance imaging can identify silent infarcts, cerebral microbleeds, periventricular white matter hyperintensities and perivascular spaces, which have been shown to predict a higher risk of stroke 8. Subtle alterations in the microstructure of normal-appearing white matter, independent of prevalent vascular lesions also predicts the risk of stroke 9. However, these techniques cannot directly image endothelial cells. We have pioneered corneal confocal microscopy as a rapid non-invasive ophthalmic imaging technique to image the corneal nerves. Whilst we have predominantly demonstrated an abnormality in the corneal nerves in a range of peripheral neuropathies 10, more recently we have shown an abnormality in central neurodegenerative conditions including Parkinson's disease 11 and multiple sclerosis 12. Furthermore, in our recent study we showed that people with acute ischemic stroke also had a reduction in corneal nerve fibers 13. In the present study, we have undertaken corneal confocal microscopy and automated quantification of endothelial cell density, area and perimeter as well as the degree of polymegathism and pleomorphism and related it to corneal nerve morphology and vascular risk factors in a cohort of patients admitted with acute ischemic stroke. Aim Corneal confocal microscopy can identify alterations in corneal endothelial cell morphology and neuronal deficit in patients presenting with an acute ischemic stroke. Methods One hundred and forty six patients admitted with an acute stroke with NGT (n = 62); IGT (n = 34) and T2DM (n = 50) and 18 age-matched healthy control participants underwent corneal confocal microscopy. There was a significant reduction in corneal endothelial cell density and an increase in endothelial cell area and perimeter in stroke patients with NGT (P = 0.002, P = 0.001, P = 0.002), IGT (P = 0.030, P = 0.028, P = 0.06) and T2DM (P<0.001, P<0.001, P = 0.001) compared to controls, respectively, with no significant difference in polymegathism and pleomorphism in stroke patients compared to healthy controls. There was a significant reduction in CNFD, CNBD and CNFL in stroke patients with NGT (P = 0.016, P = 0.001, P = 0.016), IGT (P = 0.007, P = 0.005, P = 0.007) and T2DM (P = 0.002, P = 0.008, P = 0.002) compared to controls, respectively. Diastolic blood pressure correlated with endothelial cell density (P = 0.01), endothelial cell area (P = 0.02) and endothelial cell perimeter (P = 0.01). Endothelial cell density, endothelial cell area and perimeter correlated with corneal nerve fiber density (P = 0.03, P = 0.02, P = 0.02) and corneal nerve fiber length (P = 0.02, P = 0.02, P = 0.023), respectively. Conclusion We show a reduction in corneal endothelial cell density and an increase in size which relates to diastolic blood pressure and corneal nerve loss, independent of glucose tolerance status in patients with an acute stroke. CCM allows rapid non-invasive imaging of endothelial cells to enable risk stratification of patients with stroke. References 1. Shuaib A. Alteration of blood pressure regulation and cerebrovascular disorders in the elderly. Cerebrovasc Brain Metab Rev. 1992;4:329-345 2. Heymann EP, Goldsmith D. Best approaches in the battle against globesity? Learning lessons from our experience tackling hiv-aids and tobacco smoking. JRSM short reports. 2012;3:45 3. Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. International journal of biological sciences. 2013;9:1057 4. Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, et al. Effects of bariatric surgery on human small artery function: Evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. Journal of the American College of Cardiology. 2013;62:128-135 5. Malik RA, Schofield IJ, Izzard A, Austin C, Bermann G, Heagerty AM. Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus. Hypertension. 2005;45:264-269 6. Blum A, Vaispapir V, Keinan-Boker L, Soboh S, Yehuda H, Tamir S. Endothelial dysfunction and procoagulant activity in acute ischemic stroke. Journal of vascular and interventional neurology. 2012;5:33 7. Imam YZ, D'Souza A, Malik RA, Shuaib A. Secondary stroke prevention: Improving diagnosis and management with newer technologies. Translational stroke research. 2016;7:458-477 8. Debette S, Markus H. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis. British Medical Journal. 2010;341:c3666 9. de Groot M, Verhaaren BF, de Boer R, Klein S, Hofman A, van der Lugt A, et al. Changes in normal-appearing white matter precede development of white matter lesions. Stroke. 2013;44:1037-1042 10. Alam U, Jeziorska M, Petropoulos IN, Asghar O, Fadavi H, Ponirakis G, et al. Diagnostic utility of corneal confocal microscopy and intra-epidermal nerve fibre density in diabetic neuropathy. PloS one. 2017;12:e0180175 11. Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, et al. Small fiber neuropathy in parkinson»s disease: A clinical, pathological and corneal confocal microscopy study. Parkinsonism and Related Disorders. 2015;21:1454-1460 12. Petropoulos IN, Kamran S, Li Y, Khan A, Ponirakis G, Akhtar N, et al. Corneal confocal microscopy: An imaging endpoint for axonal degeneration in multiple sclerosis. Investigative Ophthalmology & Visual Science. 2017 13. Khan A, Akhtar N, Kamran S, Ponirakis G, Petropoulos IN, Tunio NA, et al. Corneal confocal microscopy detects corneal nerve damage in patients admitted with acute ischemic stroke. Stroke. 2017:STROKEAHA. 117.018289
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Large Scale Omics Analysis of Type 2 Diabetes in the Qatari population
Authors: Noha A. Yousri, Khalid A. Fakhro, Ronald G Crystal and Karsten SuhreBackground: The prevalence of Type 2 Diabetes (T2D) in Qataris has been recently recorded (as to the Qatar Bio Bank) to be around 14-15%. T2D associated macro- and micro-vascular complications leading to retinopathy, neuropathy, nephropathy, as well as cardiovascular complications are among the most known factors leading to death. Both genetics and environmental/life style factors play roles in the pathophysiology of T2D. The advent of the Qatar Genome Project and whole genome sequencing of the Qataris will provide a wealth of genomic information on several diseases inherent in the Qataris and specifically high prevalent ones as T2D and its complications. Profiling other “omics” data as gene expression, metabolomics, proteomics, and epigenetics among others became imperative for unraveling the complex nature of T2D and the effect of both genetic and environmental factors. Objectives: In this study we focus on integrating metabolomics and genomics data for identifying their associations to T2D using nearly 1000 Qatari samples. We achieve that in the following main steps: 1-Identifying associations between metabolites and exome variants (metabolic Quantitative Trait Loci (mQTL)) in 1000 Qataris for the sake of identifying mQTLs (metabolic Quantitative trait loci) linked to both common and rare variants in Qataris. 2-Identifying T2D associated metabolites and the pathways enriched in those metabolites. 3- Investigating the associations of T2D to genes/exome variants linked to T2D through the identified mQTLs (step 1). Materials and Methods: Genomics Data: 1000 samples were collected from Qatari individuals (50% with T2D), where DNA was extracted and used for both whole exome sequencing (n = 614) and genotype arrays (n = 382)(4 samples were removed after quality control, leading to 996 samples in total). Exome and array data were imputed after being filtered (MAF> = 0.05, pHWE>10-6, genotype call rate > = 98%) based on phased 108 Qatari whole genomes as a reference panel, using shapeit and Impute2 software packages. A total of 1.6 million variants from the imputed exome were used for discovery analysis of the mQTLs and the array data was used for replication. Metabolomics Data: Serum samples for the 1000 samples were used for profiling metabolomics using a recent advanced Metabolon platform (DiscoveryHD4). This platform utilized a Waters ACQUITY ultra-performance liquid chromatography (UPLC) and a Thermo Scientific Q-Exactive high resolution/accurate mass spectrometer interfaced with a heated electrospray ionization (HESI-II) source and Orbitrap mass analyzer operated at 35,000 mass resolution. A total of 1303 metabolites were measured on that platform, and we were only left with a total of 826 metabolites (including 249 unknown metabolites) for the analysis after quality control (missing values < 20%, and outliers removed). Association Analysis: Linear regression models were used for computing associations between Metabolites and SNPs, as well as between metabolites and T2D after correcting for covariates. Results For metabolomics – Exome wide associations [Yousri et. al 2017], we discovered and replicated 21 unique mQTLs associated with common variants (MAF > 5%) and discovered another 12 mQTLs associated with rare variants using burden tests and single variant analysis. Overall, 45% of the discovered loci are novel ones. We also replicated 19% of the known mQTLs in European populations using the discovery cohort. Regarding metabolomics of T2D, we identified 190 metabolites associated with T2D, spanning pathways of fatty acid metabolism, phospholipids, sphingolipids, phenylalanine and tyrosine metabolism among others, and where 40% of the metabolites were newly identified (new to our previously reported T2D metabolites in different biofluids [Yousri et al 2015]). We also identified several associations between genes known to be associated with T2D and T2D associated metabolites. In summary, we have both identified mQTLs from large scale metabolomics (m = 826) and whole exome sequencing, and identified T2D metabolites using a large sample set (∼1000 samples), and used those to reveal the links between an intermediate phenotype – metabolite - and the genes/variants known to be associated with T2D. This is considered the first time this study is done in the Qataris integrating omics data on a large scale. References: [Yousri et. al 2017] Noha A. Yousri, Khalid A. Fakhro, Amal Robay, Juan L. Rodriguez-Flores, Robert P. Mohney, Hassina Zeriri, Tala Odeh, Sara Abdul Kader, Eiman Aldous,Gaurav Thareja, Manish Kumar, Alya Al-Shakaki, Omar M. Chidiac,Yasmin Mahmoud, Jason G. Mezey, Joel Malek,Ronald G. Crystal5, Karsten Suhre. “Whole Exome Sequencing identifies common and rare variant Metabolic Quantitative Trait Loci in a Middle Eastern Population”. Accepted in Nature Communications. [Yousri et al 2015] Noha A. Yousri, Dennis O. Mook-Kanamori, Mohammed M. El-Din Selim, Ahmed H. Takiddin, Hala Al-Homsi, Khoulood A.S. Al-Mahmoud, Edward D. Karoly, Jan Krumsiek, Kieu Thinh Do, Ulrich Neumaier, Marjonneke J. Mook-Kanamori, Jillian Rowe, Omar M. Chidiac, Cindy McKeon, Wadha A. Al Muftah, Sara Abdul Kader, Gabi Kastenmüller, Karsten Suhre, “A systems view of Type 2 Diabetes-associated metabolic perturbations in saliva, blood and urine at different time-scales of glycemic control”, Diabeteologia, August 2015.
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Management of Chronic Diabetic Foot Ulcers at Primary Care Level in Qatar :An Alternative Paradigm in Wound Healing
More LessBACKGROUND AND AIMS: Chronic Diabetic footulcers (CDFU) are associated with increased morbidity, mortality especially indeveloping countries. This cohort study assess the efficacy (CDFU)management at primary care & identifypredictive criteria of failure. METHODS: We conducted a 5-year retrospective cohort study withprospective long-term follow-up of all patients with (CDFU) who presented to Umgwalinah Health Centre, Doha, Qatar. Average follow-up was 1 year. Failure of healing of (CDFU) was themain outcome measure.Independent predictor variables were selected by logisticregression analysis. RESULTS: A total of 126 patients with diabetes were managed forvarious foot lesions as follows. Five patients (4%) of 126 underwent immediate amputation. Primary care led approach was successful for 91(92.86%) of 98 neuropathic ulcers, 3(30%) of 10 neuro-ischemic ulcer, 2(66%) of 3 Charcot foot ulceration, 4(100%) of 4 patients with second degree burns & 6(100%) of 6 traumatic foot ulceration or (P<.001,chi2 for trend).Independent factors predictive of failure to heal were presence of osteomyelitis(odds ratio [OR] = 1.6, 95% confidence interval [CI], 1.0-1.3), increased Hemoglobin A1C level (OR = 1.002; 95% CI, 1.2-1.3), severe peripheral vascular disease(OR = 1.0, 95% CI,1.0-1.03),prior hospitalization for(CDFU) (OR = 1.4; 95%CI, 1.2-1.6) & gangrenous lesion(OR = 1.7; 95% CI,1.3-2.1). No side effects were reported and there was a high level of satisfaction (patients and staff). CONCLUSIONS: Primary care based management of (CDFU) is efficacious, safeand acceptable. These findings may lead to a substantial reduction in the costof (CDFU) in the third world. Future comparative studies utilizing randomized controlled trials must be conducted in order to accurately assess the efficacy of primary care in managing (CDFU).
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Antidiabetic and Toxicological studies of ethylacetate and nhexane fractions of Gymnema sylvestre
More LessGymnema sylvestre is a medicinal plant that is used in the folkloric treatment of diabetes mellitus and the management of its complications. This study was aimed at evaluation of antidiabetic and toxicological effects of ethylacetate and n-hexane fractions of Gymnema sylvestre whole plant. Diabetes was induced in Swiss albino rats by single intraperitoneal administration of 110 mg/kg bodyweight of alloxan monohydrate. Rats in their respective groups were orally administered 100, 300 and 600 mg/kg bodyweight of ethylacetate and n-hexane fractions of the plant daily while the standard drug group received 100 mg/kg bodyweight of metformin. The treatment lasted for fourteen days and on the fifteenth day, animals were anaesthetized and euthanized. Blood samples were collected by carotid puncture for biochemical analysis. In the subchronic toxicological aspect of the study, rats in their respective groups were administered 100, 300, 600 mg/kg bodyweight of the extracts daily for twenty one days and the experiment was terminated on the twenty second day. All the extracts were able to reduce the blood glucose of diabetic rats with 300 mg/kg bodyweight of ethylacetate fraction having higher reduction at 82%. All diabetic rats showed decrease in bodyweight when compared with normoglycemic group. There was significant (p<0.05) reduction in the total cholesterol, triacylglycerol, low density lipoprotein and a concomitant increase in the values of high density lipoprotein in all treated groups when compared with diabetic untreated (negative control). The activity of serum liver enzymes (?- glutamine transpeptidase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) and bilirubin significantly decreased (p<0.05) compared with the diabetic untreated group. Levels of total protein in the treated groups did not differ from the normoglycemic group, while there was a reduction in the concentration of albumin of ethylacetate fraction in a dose dependent manner. All treated groups gave urea and creatinine values that showed no significance differences (p>0.05) with the normoglycemic group. The electrolytes showed significant differences (p<0.05) in all treated groups when compared with the normoglycemic group. There was significant difference (p<0.05) in all the biochemical parameters carried out on the subchronic toxicity test with rats administered ethylacetate and n-hexane fractions of G. sylvestre. The hematological parameters (red blood cell, mean cell volume, mean corpuscular hemoglobin concentration, packed cell volume, hemoglobin) showed no significant difference but a non significant difference in the white blood cell of rats administered with the extract. Therefore, extracts of G. sylvestre might be useful for management of diabetes mellitus and other abnormalities associated with this metabolic disorder
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Generation of a Novel Population of Pancreatic Multipotent Progenitor Cells Expressing NKX61
Authors: Essam Abdelalim, Idil I. Aigha, Ahmed K. Elsayed and Bushra MemonDiabetes is a metabolic disease caused by the loss or impaired function of insulin-producing pancreatic β-cells. Different therapeutic strategies aim to restore the endogenous production of insulin rather than the cornerstone insulin injections treatment. Human pluripotent stem cells (hPSCs) have been proposed as an unlimited source for cell-based therapy of diabetes through the directed differentiation into functional pancreatic β cells. Step-wise differentiation protocols based on developmental biology of pancreas, have led to the generation of insulin-producing β cells. However, the majority of the cells produced were poly-hormonal as they expressed other hormones in addition to insulin and have failed to respond when challenged with glucose. The coordinate expression of particular transcription factors (TF) in distinct stages governs the differentiation of hPSCs into insulin β cells. Pancreatic and duodenal homeobox protein (PDX1) is a crucial TF required for pancreas development. On the other hand, homeobox protein NKX6.1 is a potent bi-functional TF that is essential for β cells maturation, proliferation and insulin metabolism. The dual expression of PDX1 and NKX6.1 during multipotent progenitor cell (MPC) stage is vital for guiding the cells towards functional β cells lineage. However, cells expressing PDX1 but lack NKX6.1 expression tend to take the poly-hormonal path. This guided the differentiation protocols to focus on enriching MPC population co-expressing PDX1 and NKX6.1. The aim of this study was to further explore different MPC populations in terms of PDX1/NKX6.1 expression. We used two different differentiation protocols to differentiate hESCs and hiPSCs into MPCs. The mRNA and protein expressions of the generated MPCs were analyzed using immunocytochemistry, RT-PCR, and flow cytometry. Our results showed that hPSCs were successfully differentiated into the conventional (PDX1+/NKX6.1+) and (PDX1+/NKX6.1-) MPC populations. The efficiency of differentiating hPSCs into PDX1+/NKX6.1+ MPCs has varied between the two used protocols. Immunofluorescence staining has unveiled the generation of a novel population that expressed NKX6.1 independently of PDX1 (PDX1-/NKX6.1+) in both hESCs and hiPSCs. This is surprising considering that PDX1 was reported to bind to the promoter of NKX6.1 gene and is needed for NKX6.1 expression. Furthermore, using our optimized protocol, this uncharacterized subset of MPCs was enriched and found to exhibit a pattern of three-dimensional (3D) aggregates that were consistently (PDX1-/NKX6.1+) and surrounded by either (PDX1+/NKX6.1+) or (PDX1+/NKX6.1-) MPCs. To understand and characterize this unique population, we examined the expression of other TFs including endocrine precursors markers Chromogranin A (CHGA) and NKX2.2. CHGA was found to be expressed in the same areas that were positive for NKX6.1 and PDX1. However, the 3D structures that were PDX1-/NKX6.1+ did not co-express CHGA. On the contrary, few cells of these 3D aggregates co-expressed NKX2.2, suggesting that this population may have an undefined role in the development of MPCs into endocrine progenitors. These findings showcase a novel population of NKX6.1 expressing MPCs that did not require PDX1 expression at this stage. Moreover, this population may retain an alternative path towards pancreatic islet cells development that is independent of PDX1. A thorough characterization of this population is needed to explore the regulatory gene network controlling their lineage specification.
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Enhancement of differentiation of multipotent pancreatic β cell precursors from human embryonic stem cells
Authors: Essam Abdelalim, Bushra Memon, Manale Karam and Sara Al-KhawagaScalable production of human pluripotent stem cell (hPSC)-derived β cells in vitro would greatly facilitate transplantation therapy and drug discovery for treating diabetes. Employing step-wise differentiation protocols, hPSCs can be differentiated through consecutive stages of endoderm, foregut, pancreatic and endocrine progenitors to ultimately give insulin secreting β cells. Pancreatic progenitors co-expressing the two key transcription factors (TFs), PDX1 and NKX6.1, are recognized as the indispensable precursors of functional, mono-hormonal β cells. Here, we established an optimized protocol for maximizing PDX1+/NKX6.1+ co-positive pancreatic progenitors from hESCs in monolayer culture and increasing their proliferative capacity. Our technique of dissociating densely formed endodermal cells and re-plating them in lower densities on fresh matrigel matrix followed by an augmented duration of retinoid and FGF10 signaling strikingly increased the expression of NKX6.1, which is exclusive only to β cells amongst all endocrine cells. This high induction of NKX6.1 resulted in an increased proportion of PDX1+/ NKX6.1+ population, generating up to >90% PDX1+/ NKX6.1+ co-positive progenitors in monolayer, higher than previously published protocols. In contrast to multiple studies showing negligible induction of NKX6.1 at lower densities, we provide evidence that higher folds of NKX6.1 can be induced in dissociated cells re-plated lower densities compared to aggregations in non-dissociated culture if the duration of retinoid and FGF signaling is prolonged. Our optimized protocol enhanced pancreatic differentiation efficiency by up-regulating pancreatic progenitor TFs such as PDX1, SOX9, HNF6 and FOXA2 and increased the mRNA levels of endocrine TFs such as NEUROG3, NKX2.2 and NEUROD1. Additionally, we show that manipulating cell-cell attachment following endoderm generation in vitro during pancreatic differentiation dramatically inhibited alternate hepatic fate specification by down-regulating hepatic markers like AFP and ALB expression in our optimized protocol in comparison to recently published protocols for generating pancreatic progenitors. Notably, cell cycle and BrdU incorporation assays revealed that our method increased the proliferative capacity of pancreatic progenitors throughout the differentiation stages by increasing the fraction of cells entering S phase of cell cycle and a comparative increase in Ki67 expression, the proliferation marker. As a result, we obtained >70% Ki67+ /SOX9+ pancreatic progenitors in monolayer confirming an increased self-replicating capacity of the generated PDX1+/ NKX6.1+ progenitors. Furthermore, using our optimized protocol for pancreatic differentiation, we were able to enrich a novel and uncharacterized NKX6.1+ /PDX1- population, devoid of Chromogranin A (CHGA) expression, which are therefore proposed to be more mature precursors of β cell. This population re-arranged themselves in embedded, highly compact three-dimensional structures that showed high expression of Ki67. Continuation of our optimized protocol into endocrine differentiation stage validated the ability of our PDX1+/ NKX6.1+ to generate NGN3+/ NKX6.1+ co-positive endocrine progenitors in vitro with a high expression of CHGA and NKX2.2. Therefore, here we show that manipulating the cellular density, cell-cell attachment and cues from extracellular matrix plays a major role in improving pancreatic differentiation efficiency and proliferation thereby providing a cost-effective method for generating pancreatic progenitors in vitro in adherent culture. Indeed, our novel method for maximizing PDX1+/ NKX6.1+ progenitors from hPSCs in monolayer culture could serve as a source of highly proliferative pancreatic progenitors aiding scalable production of functional β cells in vitro.
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Impact of a Collaborative Pharmaceutical Care Service among Patients with Diabetes in Qatar Petroleum Healthcare Center Dukhan: A Multiple Time Series Study
Authors: Ahmed Awaisu, Sara Abdulrhim, Rana Saleh, Mohamed Abdelazim, Hend Alraey, Ahmed Babiker and Nadir KheirBackground: Diabetes mellitus is a highly prevalent non-communicable disease worldwide. The prevalence of diabetes in Qatar exceeds the prevalence of diabetes in the Middle East and North Africa region and the globe. Similarly, diabetes-related complications and mortality are dramatically increasing worldwide. Poor health outcomes and debilitating consequences can result from inadequate control of diabetes. Previous studies have demonstrated the benefit of pharmaceutical care services on outcomes of diabetes. No studies were done in Qatar regarding this issue. Therefore, the objectives of this study were to: (1) characterize the clinical profile of patients with diabetes attending an ambulatory care clinic at Qatar Petroleum (QP) Medical Center including diabetes-related comorbidities and complications; (2) evaluate the impact of a Comprehensive Pharmaceutical Care Service (CPCS) on glycemic control [glycated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)]; (3) evaluate the impact of the CPCS on diabetes comorbidities including lipid profile [low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC)], systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) and; (4) classify the drug-related problems (DRPs) identified by pharmacists during the follow-up period. Methods: This was a multiple time series, observational, retrospective, pre-post study among patients attending diabetes clinic at QP Medical Center in Dukhan. Primary clinical outcome measures including HbA1c, FPG, weight, BMI, SBP, DBP, and lipid profile were measured at baseline, 6 months, and 12 months after receiving the CPCS through a retrospective chart review of electronic medical records for the year 2016. The secondary outcome measure, the types of DRPs identified by pharmacists, was collected over the period of 12 months of initiating the CPCS and categorized into a predetermined classification system. Data analyses were performed using IBM SPSS® version 23.0. Primary clinical outcome measures were analyzed inferentially using Repeated Measure ANOVA to determine the impact of the intervention. Sociodemographic characteristics, basic clinical characteristics, baseline and current medications regimens, and types of DRPs identified by pharmacists were analyzed descriptively using frequencies, percentages and means as appropriate. Results: A total of 96 eligible patients with diabetes were included in the study. CPCS significantly improved the following parameters from baseline to 6 and 12 months: HbA1c (8.5%, 7.4%, 7.1%, respectively; P <0.001), FPG (154.1 mg/dL, 115.4 mg/dL, 112.8 mg/dL, respectively; P <0.001), weight (79.9 Kg, 78.3 Kg, 76.9 Kg, respectively; P <0.001), BMI (29.1 Kg/m2, 28.5 Kg/m2, 28.1Kg/m2, respectively; P <0.001), SBP (140.2 mmHg, 129.1 mmHg, 125.3 mmHg, respectively; P <0.001) and DBP (84.7 mmHg, 79.5 mmHg, 76 mmHg, respectively; P <0.001). However, no significant reductions from baseline to 6 and 12 months were observed in LDL-C (2.7 mmol/L, 2.8 mmol/L, 2.7 mmol/L, respectively; P = 0.702), HDL-C (1.2 mmol/L, 1.2 mmol/L, 1.3 mmol/L, respectively; P = 0.551), TG (1.6 mmol/L, 1.7 mmol/L, 1.7 mmol/L, respectively; P = 0.728), and TC (4.3 mmol/L, 4.3 mmol/L, 4.1 mmol/L, respectively; P = 0.101). The most prevalent three DRPs identified were lack of understanding of the medication (39.8%), inappropriate dose, form, schedule, route, or method of administration (17.3%), and actual and potential adverse events (14.3%). Conclusion: The provision of CPCS in a primary healthcare setting in Qatar improves clinical outcomes in patients with diabetes over a 12-month follow-up period. Future studies are needed to determine the long-term outcomes of CPCS.
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NonInvasive Wearable Sensors to detect onset of hypoglycemia: A Literature Review
Authors: Karim Zahed, Farzan Sasangohar, Yibo Zhu, Ranjana Mehta, Madhav Erraguntla, Mark Lawley and Khaled QaraqeIntroduction: Hypoglycemia is a prevalent condition where diabetic patients experience low blood glucose. There are approximately 300 million diabetic patients in the world; at least 30 million of those are in the United States. Diabetic patients facing hypoglycemia continue to grow but the condition worsens as patients lose awareness the more episodes that occur. Mild hypoglycemia is characterized as blood glucose below 70mg/dl and severe as blood glucose below 40mg/dl (Kalra et al., 2013). Severe hypoglycemia may cause loss of patient's awareness and in some cases fatality. Loss of awareness leads to a 6-fold increase in the risk of death. While in most cases hypoglycemia is treated through medication and diet (e.g. fast-acting carbohydrates), a popular technology among diabetic patients; especially those with hypoglycemia unawareness; is continuous glucose monitors (CGM). While CGMs have shown promise, these devices are expensive, invasive, and not always accurate throughout the day (Bay et al., 2013). Hypoglycemic events are associated with several signs and symptoms such as fatigue, sweating, and pale skin, but tremors seem to be a prevalent symptom as well. One study has reported that around 20% of hypoglycemic patients stated that trembling is the first symptom they notice indicating low blood sugar (Muhlhauser, 1991), and another showed that 77.5% of diabetic patients who are aware of their symptoms experience tremors (Berlin, 2005). Our research aims at investigating the efficacy of using hand (or leg) tremor to predict the early onset of hypoglycemic events. Work is in progress to design and develop a non-invasive sensor-based wearable system that detects hypoglycemic tremor with high sensitivity and specificity. Method: A systematic review of literature is in progress to search variety of medical and engineering databases to identify research related to hypoglycemia detection, wearable sensors, and tremor. The studies considered are those pertaining to diabetic patients who have been assessed for the symptoms of hypoglycemia and the sensors used in order to predict a hypoglycemic episode. One of the main objectives of the study is to understand hypoglycemia and its symptoms, and to document technological interventions, related detection methods and sensors, as well as their shortcomings and opportunities. We hypothesize that tremor has not been used for hypoglycemia detection. The research is motivated by the preliminary review evidence that suggests current sensor-based technologies to address diabetes and hypoglycemia suffer from low patient engagement and satisfaction due to intrusiveness, low accuracy, and price. Results: While the review is in progress, we expect to have completed the search by January and plan to present the comprehensive findings at the conference. Our preliminary findings suggest a large research gap in non-intrusive technologies and methods to detect hypoglycemic events. While a frequency band of 10-14 Hz in the wrist for hypoglycemic tremors has been suggested in the literature (Rana & Chou, 2015), there is very little research done on utilizing this phenomenon to predict hypoglycemia. Most research relies on other symptoms such as skin conductance and body temperature which have been shown to cause inaccurate predictions (Howsmon & Bequette, 2015). In understanding the tremors, it is important to consider at the time the tremors start to occur in relation with particular activities, food consumption, and blood sugar; as well as the location of these tremors and their prevalence. The current review found studies that assess and promote user-centered design, and the usability of wearable sensors. This includes usability studies, human factors and FDA requirements, and other recommendations to be incorporated into developing a wearable sensor. Wide range of factors related to patient comfort and usability were identified, they include optimizing between battery life and data processing, size, location on the body. These findings are in line with other studies such as those done on wearable sensors for detection of Parkinson's disease (Rigas et al., 2012). Despite these preliminary findings, comprehensive guidelines to design for wearability had not been offered. Based on these and upcoming findings a taxonomy for design criteria for wearability will be presented. Conclusion: Diabetes is a growing epidemic and the occurrence of hypoglycemia for diabetic patients is prevalent and potentially fatal. Detecting the onset of hypoglycemia is vital and tremors seem to be a viable symptom. Our preliminary findings from a systematic literature review suggest a general gap in technological interventions for early detection and recognition of hypoglycemic events. In particular, our current findings show that tremor detection technologies have not been utilized in this domain. Sensors assessing tremor frequency could be an alternative approach to current sensors in the market and may contribute to non-intrusive, high accuracy and low cost solutions. This review will inform a taxonomy of design considerations for non-intrusive wearable technologies. Our future work aims at addressing this gap by utilizing a user-centered design of a wearable device to detect the early onsets of hypoglycemic events by measuring tremor.
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Hypoglycemic and Cardioprotective Effects of Methanol Extracts of Gymnema Sylvestre Plant and Annona Senegalensis Carpels Used in the Folkloric Treatment of Diabetes
More LessThe epidemic of diabetes has major health and socioeconomic impacts especially in developing countries, and subjects with diabetes have increased risk of disease affecting the heart, blood vessels, eyes, kidneys and nerves. Whole Gymnema sylvestre plant and Annona senegalensis carpels are used in the folkloric treatment of diabetes mellitus and the management of its attendant complications. Diabetes was induced in Swiss albino rats by single intraperitoneal administration of 11 mg/kg bodyweight of alloxan monohydrate and rats with blood glucose ≥ 206 mg/dl were considered diabetic. Rats in their respective groups were orally administered 100, 300 and 600 mg/kg bodyweight of extracts of either Annona senegalensis carpels or Gymnema sylvestre daily for fourteen days while the standard drug group received 100 mg/kg bodyweight of metformin for the same period. The normoglycaemic (positive control) and the diabetic untreated (negative control) groups received 0.5 ml normal saline. The animals were euthanized on the 15th day and blood samples were collected by carotid puncture for biochemical analysis. The 600 mg/kg bodyweight dose of Gymnema sylvestre and 300 mg/kg bodyweight dose of Annona senegalensis carpels respectively reduced the blood glucose of diabetic rats by 76.45 % and 72.01 %. All treatment groups of Gymnema sylvestre gave urea and creatinine values that showed no significance differences (p>0.05) with the normoglycemic (positive control) group while urea and potassium ion (K+) concentrations at 600 mg/kg bodyweight of Annona senegalensis carpels extract reduced significantly as the blood glucose progressively declined. Chloride ion (Cl− ) concentrations in the treatment groups for both extracts did not differ from the normoglycemic (control) group, while there was a reduction in the concentrations of potassium ion (K− ) of 100 and 300 mg/kg bodyweight treated groups of Gymnema sylvestre extract. There was also a reduction in the concentration of sodium in all treated groups when compared with the normoglycemic group. The concentrations of total cholesterol, triacylglycerol, low density lipoprotein also reduced regressively as the treatment days progressed and a concomitant increase in the values of high density lipoprotein in all treated groups for both extracts when compared with diabetic untreated (negative control). The crude methanol extracts of Gymnema sylvestre and Annona senegalensis carpels were able to lower the blood glucose of diabetic rats and ameliorate the attendant hyperlipidemic effect associated with diabetes.
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Endothelila based cardiac regeneration
Authors: Arash Rafii, Jennifer Pasquier, Khaled Machaca, Raphael Courjaret and Charbel Abi KhalilBackground - The regenerative ability of the heart is very low, making patients with myocardial damage potential candidates for cell-based regenerative therapy. Pluripotent human embryonic stem cells (hESC) are a promising source of repopulating cardiomyocytes (CMs). While the quantity of CMs obtained is no longer a limitation in current differentiation protocols, their inotropy needs to be improved.We have creaated in Doha since the last 10 years a unique plafrm based on endothelial feeder as an instructive niche for organ regeneration. We have been ablse so for to demonstrate efficient regeneration in liver lung and HSCs regeneration. Here we hypothesized that we could improve maturation of CMs and facilitate electrical interconnections by creating a mixture of cell types that more closely resembles heart tissue - i.e. containing both endothelial cells (ECs) and cardiomycocytes. Using our unique endothelial platfrom we demonstrated an increased in differentiated functional CM. CMs formed under these conditions displayed a higher rate of contraction. The co-culture with endothelial cells led to synchronized beating relying on the endothelial network as illustrated by the loss of synchronization upon the disruption of endothelial bridges. Hence we created a unique platfrom allowing to expand functional cardiomycocytes that could be potentially used in cell therapy protocol. Our research promotes the concept of organoid based cell therapy.
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Screening for diabetic retinopathy with a deep learning network: Evaluation of retinal images from the Qatar Biobank
Authors: Patrick De Boever, Bart Elen, Arnout Standaert and Rayaz A MalikDiabetic retinopathy (DR) is the leading cause of impaired vision and blindness in working age adults. Regular eye screening is advised to prevent progression to blindness. However, screening programs are labor- and capital-intensive and suffer from limited access to trained professionals. Artificial intelligence has been employed to develop algorithms for automated classification of retinal images. We developed an ensemble model of two deep convolutional neural networks to score DR in fundus images. The model was trained using tens of thousands images from a public database and allows the determination of DR stage, as well as referable DR. The model was validated on 1748 fundus images from the Messidor-2 database. All 190 patients with referable DR were successfully detected by our deep learning (DL) model (sensitivity 100%, 95%CI 98.1%-100%). The model labelled 444 of the 684 diabetes patients without referable DR accordingly (specificity 65.0%, 95%CI 61.2%-68.5%). The DL model was further evaluated on retinal images from the Qatar Biobank. Images from 740 individuals enrolled in the Qatar Biobank were received. Image quality was poor in 72 individuals leaving 668 individuals with manually graded images which were independently analyzed using the DL model. The model scored the DR class with an accuracy of 0.88 and a precision of 0.95. Forty-two individuals (6.3%) have some form of DR and referable DR was identified in twenty-six individuals. The model for referable DR had an accuracy of 0.90 and a precision of 0.97. In conclusion, our DL model has been successfully tested on fundus images from the Qatar Biobank. The Automated Retinal Image Analysis System (ARIAS) is promising in relation to supporting medical professionals to undertake cost-effective screening, especially in the context of large population screening programs.
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Stress Granules as a possible regulator of pluripotent stem cell self renewal and differentaition
In cells subjected to environmental stresses, such as oxidative stress and heat shock (HS), dynamic ribonucleoprotein aggregates, known as Stress Granules (SGs)), are formed as a part of the cell response program. Different types of stresses control pluripotent stem cell (PSCs) ability to self renew and differentiate, indicating the possible role of SGs in regulating stem cell fate. In this study we compared the effects of oxidative (sodium arsenite (SA) and hydrogen peroxide (H2O2)) and thermal (Heat Shock) stresses on SG formation in human induced (hi) PSCs. Our aim was to examine whether these granules paly a role in regulating PSC self-renewal and differentiation. Our data showed that not all stressors induce SG formation in hiPSCs. Increasing SA concentartions, progressively increase the number of cells showing SGs, however, iPSCs treated with H2O2 exhibited no SG formation even with higher concentrations or longer periods of incubation. On the other hand, no granules were observed in cells kept at 37oC or exposed to mild HS (40oC) treatment, whereas at higher temperatures of 42oC, 100% of the cells formed SGs. Molecular analyses of the granules formed in iPSCs in response to stress conditions showed that they (i) contain the well-known SGs proteins markers (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), (ii) are present in the cytoplasm in a physical attachment to processing bodies (PBs), and (iii) are disassembled after the removal of the stress. This data confirm that these iPSCs granules are per se SGs. In addition, the formation of SGs was associated with the stimulation of eIF2α phosphorylation in hiPSCs after SA and HS, but not H2O2, which confirm the stimulation of the stress response program. To test whether pluripotent marker proteins are recruited to SGs, we perform an initial screening for several pluripotent markers and confirmed that LIN28A and L1TD1 were SG markers and identified DPPA5 as a novel pluripotent marker that was weakly recruited to SGs. Altogether, our data introduce new aspects of how hiPSCs respond to adverse environmental conditions and identify SGs as a possible regulator of pluripotent stem cell self renewal and differentiation.
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Suppression of adipocyte hyperplasia through SIRT1mediated inhibition of cMyc function
More LessYasser Majeed1, Aisha Madani1, Muneera Vakayil1, Maha Agha1, Houari Abdesselem2, Mohamed ElRayess3, Moataz Basha4, Nasrin Mesaeli1, Michael Bonkowski5, David A Sinclair5, Nayef A. Mazloum1 1. Weill Cornell Medicine-Qatar, Doha, Qatar 2. Qatar Biomedical Research Institute, Doha, Qatar 3. Anti-Doping Lab-Qatar, Doha, Qatar, 4. Hamad Medical Corporation, Doha, Qatar 5. Harvard Medical School, Boston, MA, USA. Global estimates from the World Health Organization (WHO) suggest that obesity has approximately tripled since 1975 and that over 600 million adults and 300 million children/adolescents were obese. Obesity is a major risk factor for Type 2 Diabetes (T2D) and associated disorders that affect the cardiovascular system. Insulin resistance, insufficient insulin secretion and increased blood glucose levels (hyperglycemia) are characteristic features of T2D. Together with other cardio-metabolic complications observed in T2D, hyperglycemia results in vascular disease and increased morbidity and mortality. There is therefore a worldwide health impact of T2D and its complications. Locally, the incidence of obesity and T2D in Qatar ranks among the highest in the world and is a serious public health burden. Genetic predisposition and environmental factors such as intake of calorie-rich food and a sedentary lifestyle make significant contributions to the obesity epidemic. White adipose tissue (WAT) plays a key role in the pathophysiology of obesity and its associated co-morbidities. WAT is distributed either subcutaneously or within different depots in the intra-abdominal cavity surrounding or near vital organs (viscera). WAT mass expansion observed in obesity is due to enlarged fat cell volume (hypertrophy) and increased cell number (hyperplasia). Hence, understanding how WAT function is dysregulated is essential to understanding the pathophysiology of obesity and designing improved therapeutics to treat obesity and its metabolic complications. There is little known about the molecular mechanism that drives adipocyte hyperplasia in obesity. The NAD-dependent protein deacetylase sirtuin-1 (SIRT1), a master regulator of mammalian metabolism, maintains proper metabolic functions in many tissues counteracting obesity. Our laboratory has shown that differentiated adipocytes are hyperplastic when the expression of SIRT1 is stably reduced in mouse 3T3-L1 preadipocytes. This phenotype is concomitant with altered adipocyte metabolism and increased inflammation. We also show that SIRT1 is critical in the regulation of proliferation of preadipocytes. By employing quantitative proteomics studies, we provided evidence that the molecular pathway downstream of the c-Myc proto-oncogene is affected to drive enhanced proliferation in SIRT1-silenced preadipocytes cells. Our data suggest that c-Myc is transcriptionally activated upon SIRT1 reduction leading to lower levels of p27 (cyclin-dependent kinase inhibitor) and the activation of the CDK2 (cyclin-dependent kinase 2). Remarkably, differentiated SIRT1-silenced preadipocytes show enhanced mitotic clonal expansion (MCE) phenotype along with reduced levels of p27, as well as elevated levels of c-Myc and the adipogenesis transcription factor C/EBPβ. c-Myc activation and enhanced proliferation phenotype were also observed to be SIRT1-dependent in mouse embryo fibroblasts (MEFs) and human SW872 preadipocytes. Interestingly, the stable reduction of both SIRT1 and c-Myc expression in 3T3-L1 preadipocytes did not lead to the adipocyte hyperplasia phenotype, which further confirms that SIRT1 suppresses adipocytes hyperplasia through c-Myc inhibition. Current studies are focused on investigating the in vivo relevance of Sirt1-c-myc interaction in mouse models of diet-induced obesity. We are also isolating preadipocytes from WAT collected from insulin sensitive (IS) and insulin resistant (IR) obese subjects to evaluate differences in their proliferation rates and adipogenic potential and to understand if these might be linked to altered SIRT1 and C-Myc functions. Better understanding of the molecular mechanisms of adipocyte hyperplasia will open new venues towards understanding obesity.
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Retinal blood vessel analysis using IFLEXIS software on fundus images from the Qatar Biobank
Authors: Arnout Standaert, Patrick De Boever, Bart Elen and Rayaz A MalikRetinal examination is a diagnostic pillar in ophthalmology for the early detection of eye diseases such as retinopathy (hemorrhage/exudate) and glaucoma (optic disc abnormality). Large population-based studies have shown that retinal vessel morphological quantification may be useful in predicting the development and progression of hypertension, diabetes and cardiovascular diseases (CVD). The rationale for this is that the retinal microcirculatory bed shares similar anatomical and physiological characteristics with the coronary and cerebrovascular circulations. Therefore, quantification of retinal vessel metrics may reveal insights into the development of coronary artery and cerebrovascular disease. Indeed, retinal blood vessel analysis has gained increasing interest in recent years for predicting the development of hypertension, coronary heart disease, stroke and type II diabetes. A number of software algorithms have been used to quantify retinal vessel morphology, but they require manual input and are time- and labor-intensive. Fully automated image analysis allows objective and accurate assessment of retinal vessel parameters. VITO has developed and released IFLEXIS, software for semi-automated retinal vessel analysis, which includes algorithms to determine blood vessel widths, vessel branching and vessel network complexity, integrated in a user-friendly workflow. During the Belgian Economic Mission to Qatar in March 2015, WCM-Q, VITO and Qatar Biobank signed a Memorandum of Understanding to explore the potential of retinal analysis for the early detection of retinal vessel abnormalities in subjects attending the QBB. Fundus images from 774 people attending the Qatar Biobank contained images from healthy controls, subjects with Impaired Glucose Tolerance (IGT), Hypertension (HT) and/or Type 2 diabetes (T2DM). Here, we report the utility of IFLEXIS in a subset of 597 fundus images obtained from 574 persons which could be analyzed. The following parameters were quantified: (i) FD (fractal dimension, using the box counting method), FFD (Fourier fractal dimension) and lacunarity of the vessel network, and (ii) CRAE, CRVE (central artery/vein equivalent) and AVR (artery-to-vein ratio). Analysis revealed the following mean (range) for this population: 1.39 (1.32 - 1.53) for FD, 2.75 (1.77 - 2.98) for FFD, 1.00 (0.94 - 1.08) for lacunarity, 154.73 (93.79 - 195.67) for CRAE, 233.26 (159.67 - 307.94) for CRVE and 0.67 (0.48 - 0.93) for AVR. Statistical tests for the retinal parameters reveal interesting differences between the studied disease groups. When comparing HT with control subjects, statistically significant differences were found for the CRAE (150.05 ± 2.17 versus 157.88 ± 1.91, p = 1.02 × 10-6) and the CRVE (231.74 ± 3.60 versus 238.28 ± 2.83, p = 0.031). Comparing subjects with HT and T2DM with controls also revealed significant differences in CRAE (145.15 ± 3.62 versus 157.88 ± 1.91, p = 4.66 × 10-8) and CRVE (218.47 ± 5.16 versus 238.28 ± 2.83, p = 3.31 × 10-9). This study showed the feasibility of retinal vessel analysis of standard fundus images from the QBB using IFLEXIS. Despite the fact that the fundus images were originally not taken for this purpose, IFLEXIS software can extract novel retinal blood vessel dimensions. As blood vessel analysis has been shown to be relevant for chronic disease prediction, we propose to utilize the baseline assessment to augment the Qatar Biobank database to predict incident disease in follow-up studies. Single retinal features already appear to differentiate subjects with hypertension and/or diabetes compared to controls. We will undertake quantification of a larger image data set and will perform further data analysis to refine both the diagnostic and/or prognostic use of retinal metric analysis in the QBB population. To this end, we will combine retinal vessel metrics with demographics such as age, duration of disease and other metabolic parameters and study the association with whole genome sequence patterns in this population.
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Early predictors of incipient metabolic syndrome in an Arab population
Background. Metabolic syndrome is defined by a constellation of abnormal factors that directly increse the risk for type 2 diabetes and cardiovascular disorders. the the gulf cooperation council region the prevelance of metabolic syndrome in the population is higher than in most developed countries, with generally greater rates for women, often higher than 40%. Thus, early clinical identification of patients is important to adequately implement treatments to reduce their risk of subsequent metabolic disease. Aims/hypothesis. Therefore the aims of this study were to investigate the hypothesis that in sedentry subjects, post-prandial hyperinsulinemia, despite normal levels of glucose, is an indicator of incipient diabetes. further this lesion is associated with markers of adipose and hepatic dysfunction.Methods.Forty two apparently clinically healthy residents of Qatar were studied. After a 10-hour overnight fast, subjects underwent a detailed clinical assessment, including body composition by bioimpedance, anthropometry measurments (height, weight and BMI), and blood pressure. A liquid mixed meal was administered (200 ml of 18g proteins, 17.4g fats and 40g carbohydrates: total energetic value of 400 kcal) and blood sampling carried out prior to and 30 and 120 minutes after the meal. the study was approved by the Institutional Research Ethics Committee and all subjects provided written informed consent prior to participation.Fasting serum levels of lipids (HDL-C, LDL-C,total cholesterol and triglycrides),liver (GGT,ALP,TB,DB and albumin), plasma glucose, insulin and proinsulin were also determined. HOMA-IR (homeostasis model of assessment-insulin resistance) was calculated using the foloowing formula:(fasting insulin in mIU/L *fasting glucose in mmol/L)/22.5.Serum levels of Leptin and adiponectin were measured using human 2-site ELISAs. All inter- and intra-assay CVs were less than 10%. Results.there were no differrence in age, blood pressure and body composition between the two groups. However, 48% of this population showed hyperinsulinemia in the fasting state, as well as relative hyperglycemia, hyperinsulinemia and hyperproinsulinemia 2 hour after the meal challenge.Systemic lipids and markers of liver function were comparable between the groups. while leptin was elevated in the hyperinsulinemia group (26.1 ng/ml versus 20.9 ng/ml), this did not reach significance. However adiponectin was significantly lower in this chohort (5.8 mcg/ml versus 8.5 mcg/ml, P = 0.002).significant correlation were apparent between fasting insulin concentration and height, measures of body fat as well as muscle mass. In addition fasting insulin also correlated significant with SBP, as well as all measures of glucose and HOMA-IR. interestingly fasting insulin also correlated positively and significantly with liver enzymes. inverse, but significant, association was found between insulin with HDL-C and adiponection. Most of these relationships were lost in the postprandial state.conclusions/interpretation. Thus, these data indicate that postprandial hyperinsulinemia and decreased adiponectin levels should be considered in the plethora of the altered biochemical parameters that define the metabolic syndrome. More importantly, since these biochemical alterations occur in seemingly healthy residents, they may well be considered early biomarkers on incipient metabolic syndrome. the reasons for this lesion in a young and healthy population is likely to be the consequence of a sedentry lifestyle. Exercise and training can improve both insulin resistance and increase adiponectin and should be actively advocated for this population.
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