Mahmoud Zirie

Prevalence of diagnosed and undiagnosed diabetes mellitus and its risk factors in a population-based study of Qatar

OBJECTIVE The objective of the study was to determine the prevalence of diagnosed and undiagnosed diabetes, pre-diabetes and to identify the associated risk factors in the sample of adult Qatari population. DESIGN This was a cross-sectional study. SETTING The survey was carried out in urban and semi-urban primary health care centers. SUBJECTS AND METHODS The survey was conducted from January 2007 to July 2008 among Qatari nationals above 20 years of age. Of the 1434 subjects who were approached to participate in the study, 1117 (77.9%) gave their consent. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the WHO expert group. Pre diabetes status was based on the presence of impaired fasting glucose or impaired glucose tolerance. RESULTS The overall prevalence of diabetes mellitus among adult Qatari population was high (16.7%) with diagnosed DM (10.7%) and newly diagnosed DM (5.9%). The impaired glucose tolerance (IGT) was diagnosed in 12.5%, while impaired fasting glucose was in 1.3% with a total of (13.8%). The proportion of DM was higher in Qatari women (53.2%) than in Qatari men (46.8%) and it peaked in the age group 40-49 years (31.2%). The age-specific prevalence of total DM and IGT increased with age. Risk factors were significantly higher in diabetic adult Qatari population: central obesity (p<0.001), hypertension (p<0.001), triglyceride (p<0.001), HDL (p=0.003), metabolic syndrome (p<0.001), heart diseases (p<0.001). Smoking habits and family history of DM were the major contributors for diabetes disease. The central obesity was associated with higher prevalence of DM and IFG among Qatari men and women. CONCLUSION The present study has found a moderately high prevalence of diabetes mellitus in the adult Qatari population. High proportion of pre-diabetes in Qatari adults will increase the prevalence of DM in the next few years. Smoking habits and family history of DM were the major contributors for DM. Early diagnosis of DM is of major importance to reduce the risk of these diabetes-related conditions.

Prevalence of Metabolic Syndrome According to Adult Treatment Panel III and International Diabetes Federation Criteria: A Population-Based Study

OBJECTIVE The objective of the study was to examine the prevalence of metabolic syndrome among adult Qatari population according to the revised criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF), assess which component contributed to the increased risk of the metabolic syndrome, and identify the characteristics of the subjects with metabolic syndrome. DESIGN This was a cross-sectional study. SETTING The survey was carried out in urban and semiurban primary health-care centers. SUBJECTS AND METHODS The survey was conducted from January, 2007, to July, 2008, among Qatari nationals above 20 years of age. Of the 1496 subjects who were approached to participate in the study, 1204 (80.5%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by laboratory tests. Metabolic syndrome was defined using the NCEP ATP III as well as IDF criteria. RESULTS The overall prevalence of metabolic syndrome in studied subjects was 26.5% and 33.7% according to ATP III and IDF criteria (P < 0.001). The prevalence of metabolic syndrome by ATP III and IDF increased with age and body mass index (BMI), whereas it decreased with higher education and physical activity. Also, the prevalence of metabolic syndrome was more common in women. Among the components of metabolic syndrome, central obesity was significantly higher in the studied subjects. The IDF definition of metabolic syndrome gave a higher prevalence in all age groups. The overall prevalence of metabolic syndrome and its components according to IDF criteria was higher in the studied subjects than the estimates given by the ATP III. Multivariate logistics regression analysis (ATP III and IDF) showed that age and BMI were significant contributors for metabolic syndrome. Both definitions strongly supported age and obesity as associated factors for metabolic syndrome. CONCLUSIONS The current study found a high prevalence of metabolic syndrome among Qataris. There was a steady increase in the prevalence of metabolic syndrome through the decades, independent of the definition. Age and BMI were important significant predictors for metabolic syndrome.

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

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

Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.

1,5-Anhydroglucitol in Saliva Is a Noninvasive Marker of Short-Term Glycemic Control

CONTEXT In most ethnicities at least a quarter of all cases with diabetes is assumed to be undiagnosed. Screening for diabetes using saliva has been suggested as an effective approach to identify affected individuals. OBJECTIVE The objective of the study was to identify a noninvasive metabolic marker of type 2 diabetes in saliva. DESIGN AND SETTING In a case-control study of type 2 diabetes, we used a clinical metabolomics discovery study to screen for diabetes-relevant metabolic readouts in saliva, using blood and urine as a reference. With a combination of three metabolomics platforms based on nontargeted mass spectrometry, we examined 2178 metabolites in saliva, blood plasma, and urine samples from 188 subjects with type 2 diabetes and 181 controls of Arab and Asian ethnicities. RESULTS We found a strong association of type 2 diabetes with 1,5-anhydroglucitol (1,5-AG) in saliva (P = 3.6 × 10(-13)). Levels of 1,5-AG in saliva highly correlated with 1,5-AG levels in blood and inversely correlated with blood glucose and glycosylated hemoglobin levels. These findings were robust across three different non-Caucasian ethnicities (Arabs, South Asians, and Filipinos), irrespective of body mass index, age, and gender. CONCLUSIONS Clinical studies have already established 1,5-AG in blood as a reliable marker of short-term glycemic control. Our study suggests that 1,5-AG in saliva can be used in national screening programs for undiagnosed diabetes, which are of particular interest for Middle Eastern countries with young populations and exceptionally high diabetes rates.

Plantar temperature response to walking in diabetes with and without acute Charcot: The Charcot activity response test

Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot). Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P = 0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.

Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian‐South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared with 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Premarital genetic screening in Qatar tests for only four out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.

Comparison of Efficacy and Safety of Rosuvastatin, Atorvastatin and Pravastatin among Dyslipidemic Diabetic Patients

Objectives. To investigate the efficacy and the safety of the three most commonly prescribed statins (rosuvastatin, atorvastatin, and pravastatin) for managing dyslipidemia among diabetic patients in Qatar. Subjects and Methods. This retrospective observational population-based study included 350 consecutive diabetes patients who were diagnosed with dyslipidemia and prescribed any of the indicated statins between September 2005 and September 2009. Data was collected by review of the Pharmacy Database, the Electronic Medical Records Database (EMR viewer), and the Patients Medical Records. Comparisons of lipid profile measurements at baseline and at first- and second-year intervals were taken. Results. Rosuvastatin (10 mg) was the most effective at reducing LDL-C (29.03%). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). All three statins were safe in relation to muscular and hepatic functions. In relation to renal function, atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%). Conclusion. In the Qatari context, the most effective statin at reducing LDL-C was rosuvastatin 10 mg. Atorvastatin was the safest statin in relation to renal function. Future large-scale prospective studies are needed to confirm these results.

Ethnic and gender differences in advanced glycation end products measured by skin auto-fluorescence

Background Advanced glycation end products (AGEs) have been shown to be a predictor of cardiovascular risk in Caucasian subjects. In this study we examine whether the existing reference values are useable for non-Caucasian ethnicities. Furthermore, we assessed whether gender and smoking affect AGEs. Methods AGEs were determined by a non-invasive method of skin auto-fluorescence (AF). AF was measured in 200 Arabs, 99 South Asians, 35 Filipinos and 14 subjects of other/mixed ethnicity in the Qatar Metabolomics Study on Diabetes (QMDiab). Using multivariate linear regression analysis and adjusting for age and type 2 diabetes, we assessed whether ethnicity, gender and smoking were associated with AF. Results The mean AF was 2.27 arbitrary units (AU) (SD: 0.63). Arabs and Filipinos had a significant higher AF than the South Asian population (0.25 arbitrary units (AU) (95% CI: 0.11‒0.39), p = 0.001 and 0.34 (95% CI: 0.13‒0.55), p = 0.001 respectively). Also, AF was significantly higher in females (0.41 AU (95% CI: 0.29‒0.53), p < 0.001). AF associated with smoking (0.21 AU (95% CI: 0.01‒0.41), p = 0.04) and increased with the number of pack-years smoked (p = 0.02). Conclusions This study suggests that the existing reference values should take ethnicity, gender and smoking into account. Larger studies in specific ethnicities are necessary to create ethnic- and gender-specific reference values.

The Qatar genome: a population-specific tool for precision medicine in the Middle East.

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%) and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis.