Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.

Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the ß-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting ß-cells and reducing T2DM-associated complications, among others.

Association of Biomarkers for Dyslipidemia, Inflammation, and Oxidative Stress with Endothelial Dysfunction in Obese Youths: A Case-Control Study.

Objective: The United Arab Emirates (UAE), with its characteristic local population, geography, and history, presents several risk factors for cardiovascular diseases (CVDs) in obese individuals. Obesity and its associated complications, including diabetes, atherogenic dyslipidemia, and CVDs leading to significant health risks. In the present study, "Youths" defined as young people between 18 and 22 years. We assessed dyslipidemia, inflammation, and oxidative stress biomarker levels and their association with endothelial dysfunction (ED) in both overweight/obese and normal weight youths of UAE. Methods: There were 160 youths with overweight/obese (BMI ≥ 25 kg/m2) patients and healthy age- and sex-matched normal weight (BMI ≤ 24.9 kg/m2) as controls participated in this study. The anthropometric data and blood samples were collected to assess the biomarkers for dyslipidemia, inflammation, oxidative stress, ED from all the youths. Results: The overall mean age and male-to-female ratio were 20±1.5years and 1.0:1.2, respectively. There was statistically significant difference in HDL-C (p<0.001), triglycerides (TG) (p<0.001), ApoA (p=0.002), ApoB/ApoA ratio (p=0.009) between the overweight/obese and normal weight youths. Among, inflammatory markers: hs-CRP, IL-6, TNF-α also showed significant p<0.001 and oxidative stress markers: DNA/RNA Damage, catalase and nitric oxide (NO) showed significant p<0.001 between groups. Spearman correlation of ED markers with lipid profile markers showed Vitamin C levels positively correlated with HDL-C (p<0.001) and negatively correlated with glucose (p<0.001). ICAM-1showed significant negative correlation with HDL-C (p<0.01) and ApoA (p<0.001) but positive correlation with TG (p<0.01) and HbA1c (p<0.001) among groups. Spearman correlation of ED markers with inflammatory/oxidative stress biomarkers showed Vitamin C levels negatively correlated with ferritin (p < 0.001), NO (p < 0.001), GGT (p < 0.001), and ALT (p < 0.001) levels. The ICAM-1showed significant positive correlation with hs-CRP (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.01), GGT (p < 0.05), and ALT (p < 0.05) in both groups. Conclusion: This study revealed a strong link between the biomarkers of dyslipidemia, inflammation, and oxidative stress with ED in overweight/obese patients. This study might be used to predict future cardiovascular events in this population.

Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. Method: In this case-control study we recruited 126 adolescents (13-22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. Results: The mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37-5.64; p = 0.005), LDL (2.66, 95%CI:1.19-5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57-19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. Conclusion: In this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.

Circulating ceramide levels and ratios in Emirati youth under 18 years: associations with cardiometabolic risk factors.

BACKGROUND: Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. OBJECTIVES: This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. METHODS: Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5-17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. RESULTS: We validated a high-throughput methodology using LC-MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12-0.29 µmol/L), CerC18:0 (0.019-0.067 µmol/L), CerC22:0 (0.102-0.525 µmol/L), CerC24:0 (0.65-1.54 µmol/L) and CerC24:1 (0.212-0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P < 0.05) between this score and the conventional risk factors linked to CMD, indicating its potential clinical implication. CONCLUSION: This study presents a clinical-scaled LC-MS/MS methodology for assessing clinically relevant Cer, setting reference ranges, and developing a risk score (CERT-1) for young Emirati individuals. Our findings can enhance primary risk prediction and inform the management and follow-up of CMD from an early age.

Epigenetics of conotruncal congenital heart disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation. METHODS: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597]. DISCUSSION: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.

Distribution and Association of Cardiometabolic Risk Factors Among Youth From Al Ain City, United Arab Emirates.

AIM: The purpose of this study was to examine the distribution of cardiometabolic risk factors (CMRF) among UAE University students. METHODS: The present study employed a cross-sectional design to investigate the characteristics of a sample of young individuals aged 17-26 years. The participants were exclusively drawn from the student population of UAE University. Anthropometric measurements, including weight, height, blood pressure, and random blood collection, were conducted. The statistical methods employed for comparison included the Chi-square test, Fisher's exact test, and either the two-sample t-test or the Wilcoxon rank sum test. Logistic models, both adjusted and unadjusted, were utilized to evaluate the correlation between excessive body weight and various cardiovascular and metabolic risk factors (CMRFs). All P-values were calculated using a two-sided test, and a significance level of P < 0.05 was used to determine statistical significance. The statistical computing and graphics software R (version 4.2.2) was utilized to perform all data analyses. RESULTS: Among the 269 individuals who took part in the study, a significant proportion of 55% (n=148) were identified as males. Additionally, 36% (n=97) of the participants reported having a family history of hypertension. It is worth noting that the total sample consisted of younger individuals, with a mean age of 19 years (standard deviation ±1.8). There was a significant association between overweight/obesity and male gender (p=0.003), as well as having a family history of heart attack (p=0.038), high lipid profile, and high-sensitivity C-reactive protein (hs-CRP). There was no observed correlation between a family history of hypertension and HbA1C levels in individuals with a non-normal weight. substantially elevated cardiometabolic risk variables, including systolic blood pressure (SBP) equal to or greater than 130 mmHg, diastolic blood pressure (DBP) equal to or greater than 80 mmHg, triglyceride (TG) levels equal to or greater than 150 mg/dL, high-density lipoprotein cholesterol (HDL-C) levels equal to or less than 35 mg/dL, apolipoprotein B (Apo B) levels equal to or greater than 1.3 g/L, and high-sensitivity C-reactive protein (hs-CRP) levels equal to or more than 1 mg/L, were observed to be substantially more prevalent in individuals with excess body weight compared to those with normal weight. Furthermore, the likelihood of having low HDL levels is observed to increase by 14% (Adjusted Odds Ratio = 1.14, 95% Confidence Interval [1.07 to 1.23]) among students who have extra body weight, while accounting for age and gender as controlling factors. CONCLUSIONS: Excess body weight, already in youth, was associated with increased CMRF, particularly high SBP and TG plus low HDL-C.

Cross-Sectional Association Between Body Fat Composition and Biomarkers of Inflammation and Endothelial Dysfunction in Children with Overweight/Obesity.

Background: Childhood obesity is most prevalent nutritional disorder worldwide. Studies on clinical correlations between body fat (BF) composition, lipid profile, inflammatory biomarkers, and endothelial dysfunction (ED) parameters in children from United Arab Emirates (UAE) are limited. Therefore, we aimed to study obesity pattern in children and determine clinical correlations with biomarkers. Methods: Children (6-13 years) from different schools were divided into obese, overweight, and normal groups based upon Centers for Disease Control and Prevention weight-for-age centiles study (n=166). Anthropometric, BF composition, lipid profile, inflammatory, and ED biomarkers were determined and analyzed using SPSS software. Results: The mean age and weight ± SD of participants were 10.6 ± 2.6 years and 48.2 ± 19.5 kg with 65% as overweight or obese. In normal, overweight, and obese group male were 40 (70.2%), 35 (67.3%), and 40 (70.2%) and female were 17 (29.8%), 17 (32.7%) and 17 (29.8%). There was significant difference in age (p<0.01), height (p< 0.01), weight (p< 0.01) among groups. Obesity markers (MCP-1, leptin, adiponectin) showed positive correlation with age, height, weight, WC, BF%, body fat mass (BFM), body muscle mass (BMM). A significant correlation (all p<0.01) of BMM with SBP (r=0.412), DBP (r=0.255), MCP-1 (r=0.558), adiponectin (r=0.635), hs-CRP (r=0.263), IL-6 (r=0.348), TNF-alpha (r=0.370), ICAM-1 (r=0.237), and VCAM-1 (r=0.343). The inflammatory markers (ICAM-1, VCAM-1) showed significant correlations with age, height, weight, WC, BF%, BFM, BMM. Leptin significantly (all p<0.01) correlated with age (r=0.470), height (r=0.423), weight (r=0.677), WC (r=0.606), BF (r=0.700), BFM (r=0.752), and BMM (r=0.524) and negatively correlated with TBW (r=-0.701). Adiponectin also showed a significant (all p<0.01) positive correlation with age, height, weight, WC, BF, BFM, and BMM. Conclusion: A strong association between BF composition, lipid profile, and inflammatory and ED biomarkers was observed in the study. Thus, immediate measures should be implemented to reduce risk of obesity and associated diseases.

Combined Treatment with KV Channel Inhibitor 4-Aminopyridine and either γ-Cystathionine Lyase Inhibitor ß-Cyanoalanine or Epinephrine Restores Blood Pressure, and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

The mechanism of anaphylactic shock (AS) remains incompletely understood. The potassium channel blocker 4-aminopyridine (4-AP), the inhibitors of cystathionine γ-lyase (ICSE), dl-propargylglycine (DPG) or ß-cyanoalanine (BCA), and the nitric oxide (NO) synthase produce vasoconstriction and could be an alternative for the treatment of AS. The aim of this study was to demonstrate the ability of L-NAME, ICSE alone or in combination with 4-AP to restore blood pressure (BP) and improve survival in ovalbumin (OVA) rats AS. Experimental groups included non-sensitized Wistar rats (n = 6); AS (n = 6); AS (n = 10 per group) treated i.v. with 4-AP (AS+4-AP), epinephrine (AS+EPI), AS+DPG, AS+BCA, or with L-NAME (AS+L-NAME); or AS treated with drug combinations 4-AP+DPG, 4-AP+BCA, 4-AP+L-NAME, or 4-AP+EPI. AS was induced by i.v. OVA (1 mg). Treatments were administered i.v. one minute after AS induction. Mean arterial BP (MAP), heart rate (HR), and survival were monitored for 60 min. Plasma levels of histamine, prostaglandin E2 (PGE2) and F2 (PGF2α), leukotriene B4 and C4, angiotensin II, vasopressin, oxidative stress markers, pH, HCO3, PaO2, PaCO2, and K+ were measured. OVA induced severe hypotension and all AS rats died. Moreover, 4-AP, 4-AP+EPI, or 4-AP+BCA normalized both MAP and HR and increased survival. All sensitized rats treated with 4-AP alone or with 4-AP+BCA survived. The time-integrated MAP "area under the curve" was significantly higher after combined 4-AP treatment with ICSE. Metabolic acidosis was not rescued and NO, ICSE, and Kv inhibitors differentially alter oxidative stress and plasma levels of anaphylactic mediators. The AS-induced reduction of serum angiotensin II levels was prevented by 4-AP treatment alone or in combination with other drugs. Further, 4-AP treatment combined with EPI or with BCA also increased serum PGF2α, whereas only the 4-AP+EPI combination increased serum LTB4. Serum vasopressin and angiotensin II levels were increased by 4-AP treatment alone or in combination with other drugs. Moreover, 4-AP alone and in combination with inhibition of cystathionine γ-lyase or EPI normalizes BP, increases serum vasoconstrictor levels, and improves survival in the Wistar rat model of AS. These findings suggest possible investigative treatment pathways for research into epinephrine-refractory anaphylactic shock in patients.

Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes.

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.

Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: a case-control study.

OBJECTIVE: Inflammation is a major factor in endothelial dysfunction (ED) which is the earliest predictor of cardiovascular disease and premature mortality in type 1 diabetes mellitus (T1DM) patients. This study aimed to describe the possible relationship between plasma lipids and inflammatory and ED biomarkers in young Emirati patients with and without T1DM. METHODS: This case-control study included 158 patients with T1DM and 157 healthy controls from the local population of the United Arab Emirates (UAE). Anthropometric data, clinical variables, lipid profiles, liver enzymes, HbA1c, inflammatory, and ED biomarkers were measured for all participants using sophisticated techniques and assays. RESULTS: The mean ages ± SD of patients with T1DM and healthy controls was 19.3 ± 6.4 years (59.5% females) and 9.2 ± 6.8 years (61.5% females), respectively. The mean duration of T1DM was 9.3 ± 5.7 years, with HbA1c of 8.9 ± 2.1%. BMI, WC, SBP, and DBP significantly differed between the two groups. The mean lipid profiles (HDL, TG, TC, ApoA, and ApoB), liver enzymes (GGT, ALT), inflammatory (IL-6, adiponectin, TNF-α, hs-CRP), and ED biomarker levels (ICAM-1, VCAM-1, selectin, and ET-1) were also significantly different between patients and controls. Based on Spearman's rank and logistic regression analysis, there was a significant association between elevated lipid profile, liver enzymes, inflammatory markers, and ED markers in T1DM patients compared to controls. Among the biomarkers studied, ApoA, ApoB, and TC were significantly increased in T1DM patients compared to controls. CONCLUSION: This study revealed a strong association between an elevated lipid profile and inflammatory and ED markers with T1DM, which could lead to cardiovascular events in the UAE population.

Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models: A Systematic Review.

Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.

An Extremely Rare Case of Bonneau Syndrome with Novel Cardiac and Eye Manifestations.

Bonneau or cardio-ducto-polysyndactyly syndrome is an extremely rare, life-threatening developmental defect, which has only been reported in eight patients previously. Here, we describe one such case of Bonneau syndrome in a newborn with additional novel manifestations. This late preterm (35 weeks of gestation) neonate born to parents of consanguineous marriage following a pregnancy complicated by polyhydramnios was symmetrically small for date at birth (<3rd centile for weight, length, and occipitofrontal circumference). She had the typical Bonneau syndrome features such as facial dysmorphism and polysyndactyly in addition to novel eye manifestations (microphthalmia, cataract, and vitreous hemorrhage) and cardiac defects such as D-transposition of the great arteries and pulmonary valve stenosis. The chromosomal study was normal (46, XX). The multiple congenital anomalies made the cardiac defects inoperable, and the patient died at the age of 16 days due to uncontrolled cardiac failure. A very high index of suspicion is required by pediatricians/neonatologists to identify this very rare syndrome based on presentation with known features.

Length-of-Stay in the Emergency Department and In-Hospital Mortality: A Systematic Review and Meta-Analysis.

The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14−15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.

Prevalence, Awareness, Treatment, and Control of Hypertension in the United Arab Emirates: A Systematic Review and Meta-Analysis.

BACKGROUND: Evidence for the prevalence, awareness, treatment, and control of hypertension in the United Arab Emirates (UAE) is limited. A systematic review and meta-analysis were conducted to summarize the existing knowledge regarding the prevalence, awareness, treatment, and control of hypertension in the UAE. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and Google Scholar using prespecified medical subject handling (MeSH) terms and text words to identify the relevant published articles from 1 January 1995 to 31 August 2021. Population-based prospective observational studies conducted among healthy adult subjects living in the UAE and that defined hypertension using the guidelines-recommended blood pressure (BP) cut-offs ≥ 130/80 mmHg or ≥ 140/90 mmHg were considered. RESULTS: Of 1038 studies, fifteen cross-sectional studies were included for data extraction involving 139,907 adults with a sample size ranging from 74 to 50,138 and with cases defined as blood pressure ≥ 140/90 mmHg. The pooled prevalence of hypertension was 31% (95% confidence interval (CI): 27-36), and a higher prevalence was observed in Dubai (37%, 95% CI: 28-45) than in the Abu Dhabi region (29%, 95% CI: 24-35) and in multicenter studies (24%, 95% CI: 14-33). The level of awareness was only 29% (95% CI: 17-42), 31% (95% CI: 18-44) for treatment, and 38% (95% CI: 19-57) had controlled BP (< 140/90 mmHg). CONCLUSION: This study revealed a high prevalence of hypertension with low awareness and suboptimal control of hypertension. Multifaceted approaches that include the systematic measurement of BP, raising awareness, and improving hypertension diagnoses and treatments are needed.

Medication Adherence and Treatment-Resistant Hypertension in Newly Treated Hypertensive Patients in the United Arab Emirates.

(1) Background: The present study aimed to analyze medication adherence and its effect on blood pressure (BP) control and assess the prevalence of treatment-resistant hypertension (TRH) among newly treated hypertensive patients in the United Arab Emirates (UAE); (2) Methods: A retrospective chart review was conducted to evaluate 5308 naïve hypertensive adults registered for the treatment across Abu Dhabi Health Services (SEHA) clinics in Abu Dhabi in 2017. After collecting data regarding basic details and BP measurements, patients were followed up for six months. Patients who did not reach BP targets despite taking three or more antihypertensive medications were defined as TRH; (3) Results: The overall adherence to antihypertensive treatment was 42%. At 6-month, a significant reduction in BP was observed in patients adherent to medications (systolic: -4.5 mm Hg and diastolic: -5.9 mm Hg) than those who were nonadherent to antihypertensive therapy (1.15 mm Hg and 3.59 mm Hg). Among 189 patients using three or more antihypertensive medications for six months, only 34% (n = 64) were adherent to the treatment, and only 13.7% (n = 26) reached the BP target. The prevalence of TRH was 20.1%; (4) Conclusions: Medication adherence and BP control among the participants were suboptimal. The study shows a high prevalence of TRH among newly treated hypertensives in the UAE. More extraordinary efforts toward improving adherence to antihypertensive therapy and more focus toward BP control and TRH are urgently needed.

Distribution of Cardiometabolic Risk Factors in School-Aged Children with Excess Body Weight in the Al Ain City, United Arab Emirates: A Cross-Sectional Study.

(1) Background: This study aimed to examine the distribution of cardiometabolic risk factors (CMRF) in school-aged children with excess body weight (overweight and obese) in Al Ain City, United Arab Emirates and identify the factors associated with increased cardiovascular risk factors between boys and girls. (2) Methods: A cross-sectional survey of children aged 6-17 years was conducted in Al Ain from 1 August 2019 to 31 December 2020. Binary logistic regression analysis was performed to investigate the relationship between excess body weight and CMRF between the groups and reported odds ratios (OR) with 95% confidence intervals (CI). (3) Results: A total of 966 school-aged children (490 boys and 476 girls) participated in the study, and the mean age of the children was 11.8 ± 2.9 years. The proportions of overweight and obesity were 13.5% and 10.2% in boys and 11.1% and 10.3% in girls. Higher glucose of ≥100 mg/dL (26.4%), triglycerides of ≥150 mg/dL and low-density lipoprotein cholesterol: ≥130 mg/dL (23.2%) were more prevalent in children with excess body weight. These children were at least two times more likely to have higher triglycerides levels, high total cholesterol (≥200 mg/dL) in girls (OR:2.06, 95% CI: 1.01-4.21) and low high-density lipoprotein (<35 mg/dL) in boys (OR: 2.20; 95% CI: 1.12-4.31). (4) Conclusions: Excess body weight in school-aged children was associated with increased CMRF, particularly triglycerides.

Life-threatening arrhythmias with autosomal recessive TECRL variants.

AIMS: Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL. However, phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up. METHODS AND RESULTS: An international, multi-centre retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1-22 years) and cases were followed for an average of 10.3 years (standard deviation 8.3), right censored by death in three cases. All patients on metoprolol, bisoprolol, or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype. CONCLUSION: Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and CPVT. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.

Hypertension Control and Guideline-Recommended Target Blood Pressure Goal Achievement at an Early Stage of Hypertension in the UAE.

(1) Background: The present study aimed to assess the changes in blood pressure (BP) within the first 6 months of treatment initiation in a newly treated hypertensive cohort and to identify the factors that are associated with achieving the target BP recommended by the American (ACC/AHA, 2017), European (ESC/ESH, 2018), United Kingdom (NICE, 2019), and International Society of Hypertension (ISH, 2020) guidelines. (2) Methods: We analyzed 5308 incident hypertensive outpatients across Abu Dhabi, United Arab Emirates (UAE), in 2017; each patient was followed up for 6 months. Hypertension was defined as a BP of 130/80 mmHg according to the ACC/AHA guidelines and 140/90 mmHg according to the ESC/ESH, NICE, and ISH guidelines. Multiple logistic regression was used to identify factors associated with achieving the guideline-recommended BP targets. (3) Results: At baseline, the mean BP was 133.9 ± 72.9 mmHg and 132.7 ± 72.5 mmHg at 6 months. The guideline-recommended BP targets were 39.5%, 43%, 65.6%, and 40.8%, according to the ACC/AHA, ESC/ESH, NICE, and ISH guidelines, respectively. A BMI of <25 kg/m2 was associated with better BP control according to the ACC/AHA (odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07-1.49), ESC/ESH (OR = 1.27; 95% CI = 1.08-1.50), and ISH guidelines (OR = 1.22; 95% CI = 1.03-1.44). Hypertension treated in secondary care settings was more likely to achieve the BP targets recommended by the ACC/AHA (1.31 times), ESC/ESH (1.32 times), NICE (1.41 times), and ISH (1.34 times) guidelines. (4) Conclusions: BP goal achievement was suboptimal. BP control efforts should prioritize improving cardiometabolic goals and lifestyle modifications.

Association of variants in PTPN22, CTLA-4, IL2-RA, and INS genes with type 1 diabetes in Emiratis.

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA-4, IL2-RA, and INS to T1D risk among Emiratis. The association between variants in PTPN22 (rs2476601, rs1310182), CTLA-4 (rs11571316, rs231775, rs3087243, rs1427676, and rs231727), IL2-RA (rs7090530), and INS (rs7111341) with T1D was tested in 310 Emiratis (139 T1D patients and 171 controls). A significant association was found at rs1310182, and rs2476601 both in PTPN22, rs3087243, and rs231775 both in CTLA-4, and rs12251307 in IL2-RA. Moreover, a haplotype constituted from GG and AG genotypes at rs231727 and rs231775, respectively, in CTLA-4 was significantly associated with an increased T1D risk. The cumulative effects of risk alleles for all significantly associated SNPs showed 11.8 higher relative risk for T1D for those who carry 5-6 compared to 0-1 risk alleles. This study illustrated that PTPN22, CTLA-4, and IL2-RA gene variants could confer risk alleles for T1D among the Emirati population.

Association between boarding in the emergency department and in-hospital mortality: A systematic review.

IMPORTANCE: Boarding in the emergency department (ED) is a critical indicator of quality of care for hospitals. It is defined as the time between the admission decision and departure from the ED. As a result of boarding, patients stay in the ED until inpatient beds are available; moreover, boarding is associated with various adverse events. STUDY OBJECTIVE: The objective of our systematic review was to determine whether ED boarding (EDB) time is associated with in-hospital mortality (IHM). METHODS: A systematic search was conducted in academic databases to identify relevant studies. Medline, PubMed, Scopus, Embase, Cochrane, Web of Science, Cochrane, CINAHL and PsychInfo were searched. We included all peer-reviewed published studies from all previous years until November 2018. Studies performed in the ED and focused on the association between EDB and IHM as the primary objective were included. Extracted data included study characteristics, prognostic factors, outcomes, and IHM. A search update in PubMed was performed in May 2019 to ensure the inclusion of recent studies before publishing. RESULTS: From the initial 4,321 references found through the systematic search, the manual screening of reference lists and the updated search in PubMed, a total of 12 studies were identified as eligible for a descriptive analysis. Overall, six studies found an association between EDB and IHM, while five studies showed no association. The last remaining study included both ICU and non-ICU subgroups and showed conflicting results, with a positive association for non-ICU patients but no association for ICU patients. Overall, a tendency toward an association between EDB and IHM using the pool random effect was observed. CONCLUSION: Our systematic review did not find a strong evidence for the association between ED boarding and IHM but there is a tendency toward this association. Further well-controlled, international multicenter studies are needed to demonstrate whether this association exists and whether there is a specific EDB time cut-off that results in increased IHM.