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Background Well-controlled glucose (i.e. 70-180 mg/dl) has been associated with lower mortality from COVID-19. The addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the potential negative consequences of dexamethasone-induced hyperglycemia. Methods We developed a protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19. Two of the four medical teams managing patients with COVID-19 at a tertiary center used the protocol and the other two teams continued to manage hyperglycemia at the discretion of the treating physicians (“Protocol” and “Control” groups, respectively). The glycemic control and clinical outcomes in 163 patients hospitalized with COVID-19 and dexamethasone-induced hyperglycemia between July 5th and September 30th, 2020 were retrospectively reviewed and compared between the two groups. Results Compared to the “Control” group, the “Protocol” group had higher proportions of patients with well-controlled glucose across all pre-meals and bedtime glucose readings throughout the hospitalization. The differences in glycemic control between the two groups were statistically significant for fasting glucose on days 4, 5, and discharge day; pre-lunch glucose on discharge day; pre-dinner glucose on days 3, 5, and discharge day; and bedtime glucose on day 1 (all p

Background: The ACTION IO study (NCT03584191) aimed to identify perceptions, attitudes, behaviors, and potential barriers to effective obesity care across people with obesity (PwO) and healthcare professionals (HCPs). Results from Saudi Arabia are presented here. Methods: A survey was conducted from June to September 2018. In Saudi Arabia, eligible PwO were ≥18 years with a self reported body mass index of ≥30 kg/m2. Eligible HCPs were in direct patient care. Results: The survey was completed by 1,000 PwO and 200 HCPs in Saudi Arabia. Many PwO (68%) and HCPs (62%) agreed that obesity is a chronic disease. PwO felt responsible for their weight management (67%), but 71% of HCPs acknowledged their responsibility to contribute. Overall, 58% of PwO had discussed weight with their HCP in the past 5 years, 46% had received a diagnosis of obesity, and 44% had a follow up appointment scheduled. Although 50% of PwO said they were motivated to lose weight, only 39% of HCPs thought their patients were motivated to lose weight. Less than half of PwO (39%) and HCPs (49%) regarded genetic factors as a barrier to weight loss. Many PwO had seriously attempted weight loss (92%) and achieved ≥5% weight loss (61%), but few maintained their weight loss for >1 year (5%). Conclusion: Saudi Arabian results have revealed misperceptions among PwO and HCPs about obesity, highlighting opportunities for further education and training about obesity including the biologic basis and clinical management.

Background: Obesity is considered a global chronic disease requiring weight management through lifestyle modification, pharmacotherapy, or weight loss surgery. The dramatic increase in patients with severe obesity in Saudi Arabia is paralleled with those undergoing bariatric surgery. Although known to be beneficial in the short term, the long-term impacts of surgery within this group and the sustainability of weight loss after surgery remains unclear. Objectives: We aimed to assess the long-term weight outcomes after bariatric surgery. Setting: The study was conducted at King Khalid University Hospital (KKUH), King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia. Methods: An observational prospective cohort study on adult patients with severe obesity undergoing bariatric surgery (sleeve gastrectomy (SG) or Roux-en Y gastric bypass (RYGB)) during the period between 2009 and 2015 was conducted. Weight loss patterns were evaluated pre- and post-surgery through clinical and anthropometric assessments. Absolute weight loss was determined, and outcome variables: percent excess weight loss (%EWL), percent total weight loss (%TWL), and percent weight regain (%WR), were calculated. Statistical analysis using univariate and multivariate general linear modelling was carried out. Results: A total of 91 (46 males and 45 females) patients were included in the study, with the majority belonging to the SG group. Significant weight reductions were observed at 1 and 3 years of follow-up (p &lt, 0.001) from baseline. The %EWL and %TWL were at their maximum at 3 years (72.4% and 75.8%) and were comparable between the SG and RYGB. Decrements in %EWL and %TWL and increases in %WR were seen from 3 years onwards from bariatric surgery until the study period ended. The yearly follow-up attrition rate was 20.8% at 1 year post-surgery, 26.4% at year 2, 31.8% at year 3, 47.3% at year 4, 62.6% at year 5, and 79.1% at end of study period (at year 6). Conclusion: The major challenge to the successful outcome of bariatric surgery is in maintaining weight loss in the long-term and minimizing weight regain. Factors such as the type of surgery and gender need to be considered before and after surgery, with an emphasis on the need for long-term follow-up to enssure the optimal benefits from this intervention.

Background The care of people with obesity is often suboptimal due to both physician and patient perceptions about obesity itself and clinical barriers. Using data from the ACTION-IO study, we aimed to identify factors that might improve the quality of obesity care through adoption of the 3D approach (Discussion, Diagnosis and Direction [follow-up]) by healthcare professionals (HCPs). Methods An online survey was completed by HCPs in 11 countries. Exploratory beta regression analyses identified independent variables associated with each component of the 3D approach. Results Data from 2,331 HCPs were included in the statistical models. HCPs were significantly more likely to initiate weight discussions and inform patients of obesity diagnoses, respectively, if (odds ratio [95% confidence interval]): they recorded an obesity diagnosis in their patient's medical notes (1.59, [1.43–1.76] and 2.16 [1.94–2.40], respectively); and they were comfortable discussing weight with their patients (1.53 [1.39–1.69] and 1.15 [1.04–1.27]). HCPs who reported feeling motivated to help their patients lose weight were also more likely to initiate discussions (1.36 [1.21–1.53]) and schedule follow-up appointments (1.21 [1.06–1.38]). By contrast, HCPs who lacked advanced formal training in obesity management were less likely to inform patients of obesity diagnoses (0.83 [0.74–0.92]) or schedule follow-up appointments (0.69 [0.62–0.78]). Conclusion Specific actions that could improve obesity care through the 3D approach include: encouraging HCPs to record an obesity diagnosis; providing tools to help HCPs feel more comfortable initiating weight discussions; and provision of training in obesity management. Clinical trial registration NCT03584191.

Background COVID-19 is diagnosed using RT-PCR assays of samples from nasal and oropharyngeal swabs. People with negative RT-PCR often presented with clinical manifestations of COVID-19. The data on such patients are lacking. The present study aims to characterize the patients who were suspected COVID-19 cases and tested negative in RT-PCR compared to patients who had been tested RT-PCR positive. Methods This is a retrospective, observational study of adult suspected and confirmed patients of COVID-19 admitted to King Saud University Medical City, Riyadh, Saudi Arabia, from 1st March 2020 until 30th November 2020. Laboratory confirmation is done through nasal/pharyngeal swab specimens, tested positive in RT-PCR assay. Patients with initial negative RT-PCR test results were assessed again within 48−72 h to avoid false-negative results. Patient data were extracted from the electronic medical files of each included patient using a predesigned case report form. Results The study included 488 (80.93%) patients with RT-PCR swab results positive, and 115 (19.07%) patients who were negative. Respiratory rate and diastolic blood pressure were higher among the swab-positive cases. More number of swab-negative patients had comorbidities such as coronary heart disease, chronic kidney disease, and carcinoma. Fever, cough, and shortness of breath were reported higher among the swab-positive cases. ALT and AST, and LDH levels were found higher among RT-PCR-positive patients. Serum creatinine, blood urea nitrogen and troponin were more elevated in RT-PCR-negative patients. Antibiotics, anticoagulants, and corticosteroids were used more by swab-positive patients. Significantly higher number of RT-PCR-positive patients required proning, high-flow nasal cannula, non-invasive mechanical ventilation, and invasive mechanical ventilation. Acute cardiac ischemia and death were found to be similar among the patients. However, deaths occurred significantly earlier among the swab-positive cases when compared to the swab-negative group. Conclusion Distinctive symptoms and markers of COVID-19 are more frequent among patients who had RT-PCR-positive results.

Background: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA. Methods: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region. Results: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy. Conclusions: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region.

AIMS: Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). METHODS: An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs primarily in direct patient care. RESULTS: 14,502 PwO and 2,785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of 3 (mean 6) years between the time when PwO started struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest/motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; but more referrals and follow-up appointments are required. CONCLUSIONS: Our international dataset reveals a need to increase understanding of obesity and improve education on its physiological basis and clinical management. Realisation that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations. SPONSOR: Novo Nordisk. This article is protected by copyright. All rights reserved.

Accumulating evidence suggests that subcutaneous and visceral adipose tissues are differentially associated with metabolic disorders. In obesity, subcutaneous adipose tissue is beneficial for metabolic homeostasis because of repressed inflammation. However, the underlying mechanism remains unclear. Here, we demonstrate that γ-aminobutyric acid (GABA) sensitivity is crucial in determining fat depot-selective adipose tissue macrophage (ATM) infiltration in obesity. In diet-induced obesity, GABA reduced monocyte migration in subcutaneous inguinal adipose tissue (IAT), but not in visceral epididymal adipose tissue (EAT). Pharmacological modulation of the GABA B receptor affected the levels of ATM infiltration and adipose tissue inflammation in IAT, but not in EAT, and GABA administration ameliorated systemic insulin resistance and enhanced insulin-dependent glucose uptake in IAT, accompanied by lower inflammatory responses. Intriguingly, compared with adipose-derived stem cells (ADSCs) from EAT, IAT-ADSCs played key roles in mediating GABA responses that repressed ATM infiltration in high-fat diet-fed mice. These data suggest that selective GABA responses in IAT contribute to fat depot-selective suppression of inflammatory responses and protection from insulin resistance in obesity.

Metformin is a widely prescribed medication for the treatment of type 2 diabetes mellitus (T2DM). It possesses effective roles in various disorders, including cancer, dyslipidemia, and obesity. However, the underlying mechanisms of metformin's multiple benefits are not fully understood. Herein, a mass spectrometry-based untargeted metabolomics approach was used to investigate the metabolic changes associated with the administration of a single dose of metformin in the plasma of 26 healthy subjects at five-time points; pre-dose, before the maximum concentration of metformin (Cmax), Cmax, after Cmax, and 36 h post-dose. A total of 111 metabolites involved in various biochemical processes were perturbed, with branched-chain amino acid (BCAA) being the most significantly altered pathway. Additionally, the Pearson similarity test revealed that 63 metabolites showed a change in their levels dependent on metformin level. Out of these 63, the level of 36 metabolites was significantly altered by metformin. Significantly altered metformin-dependent metabolites, including hydroxymethyl uracil, propionic acid, glycerophospholipids, and eicosanoids, pointed to fundamental biochemical processes such as lipid network signaling, energy homeostasis, DNA lesion repair mechanisms, and gut microbiota functions that could be linked to the multiple beneficial roles of metformin. Thus, the distinctive metabolic pattern linked to metformin administration can be used as a metabolic signature to predict the potential effect and mechanism of actions of new chemical entities during drug development.

BackgroundMany factors may affect wound healing in Diabetic foot ulcer, namely, microbial density, microorganisms, microbial synergy, the host immune response, and infected tissue quality.MethodologyThis study used a cross-sectional design. We assessed 38 Subjects with DFUs, 23 neuroischaimic, and 15 neuropathic, for microbiota colonizing the DFU utilizing traditional cultures and 16S gene sequencing methods. All the relevant clinical factors were collected. Wound swabs were collected for both traditional microbiological analysis, direct swab (DSM), and cultured (CM) microbiome analysis. DNA isolation, and 16SrRNA hypervariable regions were amplified. Bioinformatics analysis was performed using IonReporter Software, statistical analysis, and diversity indices were computed with vegan R-package.ResultsThe traditional microbiological method was able to detect a maximum of one or two pathogens, and, in some cases, no pathogen was detected. The total number of the observed species was 176. The number of identified species was higher in the cultured microbiome (155) than the direct swab microbiome (136). Diversity analysis indicated that biological diversity is higher in the cultured microbiome compared with the DSM. The Shannon H index was 2.75 for the cultured microbiome and 2.63 for DSM. We observed some differences in the major bacterial taxa amongst neuroischaimic and neuropathic DFU microbiomes.ConclusionsCultured microbiome is superior to both the traditional method and direct swab microbiome. The Neuroischaimic group showed higher values for the tested diversity indices than the Neuroischaimic group. Neither Cluster Analysis nor Principal Component Analysis showed apparent clustering amongst the two types of ulcers.

Khalid Siddiqui,1 Salini Scaria Joy,1 Teena Puthiyaparampil George,1 Muhammad Mujammami,1– 3 Assim A Alfadda1,3,4 1Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Department of Medicine, College of Medicine, and King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 4Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Khalid SiddiquiStrategic Center for Diabetes Research, College of Medicine, King Saud University, P.O. Box 245, Riyadh 11411, Kingdom of Saudi ArabiaTel +966 114724179 ext.1340Email ksiddiqui@ksu.edu.saBackground: Analyzing urinary biomarkers may provide better insight into pathophysiological mechanisms of diabetic kidney diseases. The study aimed to analyze the pattern of selected excreted urinary biomarkers and its correlation with albuminuria and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.Methods: A total of 185 patients with type 2 diabetes were categorized according to KDIGO guideline based on albuminuria and eGFR. The urinary markers (transferrin, KIM-1, RBP, MCP-1 and NGAL) were measured by ELISA.Results: The urinary markers were associated with eGFR (total protein/Cr, p=0.001; RBP/Cr, p=0.007; MCP-1/Cr, p=0.023; NGAL/Cr, p=0.011) and albuminuria (total protein/Cr, p< 0.001; transferrin, p< 0.001; RBP/Cr, p< 0.001; MCP-1/Cr, p< 0.001; NGAL/Cr, p=0.002).Conclusion: The urinary marker levels (total protein, RBP, MCP-1, and NGAL) are elevated with severity of kidney damage and expressed more in progressive renal impairment.Keywords: diabetic kidney disease, urinary markers, albuminuria, transferrin, kidney injury molecule-1, retinol-binding protein, monocyte chemoattractant protein-1, neutrophil gelatinase-associated lipocalin

To minimize the spread of Coronavirus Disease-2019, Saudi Arabia imposed a nationwide lockdown for over 6 weeks. We examined the impact of lockdown on glycemic control in individuals with type 1 diabetes (T1D) using continuous glucose monitoring (CGM); and assessed whether changes in glycemic control differ between those who attended a telemedicine visit during lockdown versus those who did not.Flash CGM data from 101 individuals with T1D were retrospectively evaluated. Participants were categorized into two groups: Attended a telemedicine visit during lockdown (n = 61) or did not attend (n = 40). Changes in CGM metrics from the last 2 weeks pre-lockdown period (Feb 25 - March 9, 2020) to the last 2 weeks of complete lockdown period (April 7-20, 2020) were examined in the two groups.Those who attended a telemedicine visit during the lockdown period had a significant improvement in the following CGM metrics by the end of lockdown: Average glucose (from 180 to 159 mg/dl, p 0.01), glycemic management indicator (from 7.7 to 7.2%, p = 0.03), time in range (from 46 to 55%, p 0.01), and time above range (from 48 to 35%, p 0.01) without significant changes in time below range, number of daily scans or hypoglycemic events, and other indices. In contrast, there were no significant changes in any of the CGM metrics during lockdown in those who did not attend telemedicine.A six-week lockdown did not worsen, nor improve, glycemic control in individuals with T1D who did not attend a telemedicine visit. Whereas those who attended a telemedicine visit had a significant improvement in glycemic metrics; supporting the clinical effectiveness of telemedicine in diabetes care.

Obesity is associated with numerous comorbidities along with abnormalities of the endocrine system, more commonly manifesting as dysfunctions of the thyroid gland such as goiter. Changes in weight, especially an increase, could lead to an increase in the incidence of thyroid dysfunction; however, its pathophysiology remains to be elucidated. In the present study, we aimed to interrogate the changes in the protein distribution and abundance between the lean patients and patients with obesity thyroid tissue sections through utilizing this technique. The FFPE-fixed thyroid tissue blocks from the selected cases and controls were identified and targeted for matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) analysis. Patients in the 30 to 75 years age group and undergoing total thyroidectomy for benign thyroid disease were recruited. Patients with thyroid cancers, autoimmune disorders, and other inflammatory conditions were excluded from the study. The selected patients were divided into two groups according to their BMIs: lean (BMI25) and obese (BMI35). An initial trial set was used as a pilot study for the optimization of the MALDI IMS protocol that was next applied to the selected thyroid tissues. MALDI IMS data from all the samples were aligned and statistical analysis carried out by k-means and linear discriminant analysis (LDA) classification model using principle component analysis (PCA) results were evaluated between the two groups: controls (lean) and cases (obese). Receiver operator characteristic (ROC) curves were alternatively used to calculate the variability of the identified peptides. The discriminating peptides were also independently identified and related to their corresponding proteins by using liquid chromatography and tandem mass spectrometry (LC-MS/MS) analyses. Eight peptides mainly from thyroglobulin were found to be upregulated whereas 10 others were found to be downregulated in the lean compared to the obese group. Through this technique, we will be able to better understand the relationship between the disease entity and obesity.

Objectives: Bariatric surgery provides most substantial and sustainable weight loss measures in individuals with obesity. Caloric restriction is not only intervention, changes in hormonal secretions are also leading contributory mechanisms to reduce body weight and improve the glycaemic control. The aim of this study was to evaluate the impact of gastric sleeve surgery on plasma retinol binding protein 4 (RBP4) and adipsin levels among Saudi male obese population. Methods: This prospective study was conducted in the Departments of Physiology and Surgery, College of Medicine, King Saud University. Thirty-three obese (BMI>38.3) male patients age ranged from 25 to 50 years were recruited. RBP4 and adipsin levels were analyzed before and 6-12 months after gastric sleeve surgery by ELISA along with plasma glucose, insulin, HOMA-IR and lipid profile. Results: Circulating RBP4 levels were not significantly changed by bariatric surgery (4382.85±40.35 ng before, and 4393.28±33.13 ng after surgery, p=0.842), neither did adipsin (2949.68±46.86 pg before, and 2917.90±41.90 pg after surgery, p=0.535). Segregation of study participants into two age groups, 25-35 and 35-50 years of age, revealed that before surgery older age group (35-50) had higher RBP4 levels compared to younger group (25-35) (p=0.016). However, after surgery RBP4 levels were decreased in older group but not to a significant level (p=0.174). In younger age group after surgery, there was a near significant increase in RBP4 levels (p=0.052). There were no significant changes in RBP4 levels in both age groups after surgery (p=0.461). For adipsin, there were no significant differences before and after surgery in both age groups. Insulin, BMI and HOMA-IR index were decreased after surgery, however there was no correlation with RBP4 and adipsin levels. Conclusions: The present study findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in Saudi male obese population after gastric sleeve surgery. However, a decrease in RBP4 levels in older individuals after surgery needs further investigations to understand its effect on weight and glycemic control. doi: https://doi.org/10.12669/pjms.36.7.2329 How to cite this:Alshubrami S, Al-Regaiey K, Alfadda AA, Iqbal M. Impact of Gastric Sleeve Surgery on Plasma Retinol Binding Protein 4 and Adipsin Levels in Healthy Male Population. Pak J Med Sci. 2020;36(7):1495-1499. doi: https://doi.org/10.12669/pjms.36.7.2329 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cystic fibrosis (CF), the most common lethal autosomal recessive disorder among Caucasians, is caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel gene. Despite significant advances in the management of CF patients, novel disease-related biomarkers and therapies must be identified. We performed serum proteomics profiling in CF patients (n = 28) and healthy subjects (n = 10) using the 2D-DIGE MALDI-TOF proteomic approach. Out of a total of 198 proteins identified, 134 showed a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p &lt, 0.05), including 80 proteins with increased abundance and 54 proteins with decreased abundance in CF patients. A multiple reaction monitoring-mass spectrometry analysis of six differentially expressed proteins identified by a proteomic approach (DIGE-MALD-MS) showed a significant increase in C3 and CP proteins and a decrease in APOA1, Complement C1, Hp, and RBP4proteins compared with healthy controls. Fifteen proteins were identified as potential biomarkers for CF diagnosis. An ingenuity pathway analysis of the differentially regulated proteins indicates that the central nodes dysregulated in CF subjects involve pro-inflammatory cytokines, ERK1/2, and P38 MAPK, which are primarily involved in catalytic activities and metabolic processes. The involved canonical pathways include those related to FXR/RXR, LXR/RXR, acute phase response, IL12, nitric oxide, and reactive oxygen species in macrophages. Our data support the current efforts toward augmenting protease inhibitors in patients with CF. Perturbations in lipid and vitamin metabolism frequently observed in CF patients may be partly due to abnormalities in their transport mechanism.

Background: The importance of telemedicine in diabetes care became more evident during the coronavirus disease 2019 (COVID-19) pandemic as many people with diabetes, especially those in areas without well-established telemedicine, lost access to their health care providers (HCPs) during this pandemic. Subjects and Methods: We describe a simplified protocol of a Diabetes Telemedicine Clinic that utilizes technological tools readily available to most people with diabetes and clinics around the world. We report the satisfaction of 145 patients and 14 HCPs who participated in the virtual clinic and 210 patients who attended the virtual educational sessions about “Diabetes and Ramadan.” Results: The majority of patients agreed or strongly agreed that the use of telemedicine was essential in maintaining a good glucose control during the pandemic (97%) and they would use the clinic again in the future (86%). A similar high satisfaction was reported by patients who attended the “Diabetes and Ramadan” virtual educational session and 88% of them recommended continuing this activity as a virtual session every year. Majority of the HCPs (93%) thought the clinic protocol was simple and did not require a dedicated orientation session prior to implementing. Conclusions: The simplicity of our Diabetes Telemedicine Clinic protocol and the high satisfaction reported by patients and HCPs make it a suitable model to be adopted by clinics, especially during pandemics or disasters in resource-limited settings. This clinic model can be quickly implemented and does not require technological tools other than those widely available to most people with diabetes, nowadays. We were able to successfully reduce the number of patients, HCPs, and staff physically present in the clinics during the COVID-19 pandemic without negatively impacting the patients’ nor the HCPs’ satisfaction with the visits.

To determine the prevalence and factors associated with depression and anxiety among people with and without diabetes during the coronavirus disease 2019 (COVID-19) outbreak.A cross-sectional questionnaire-based study collecting demographic and mental health data from 2166 participants living in the Arab Gulf region (568 with diabetes, 1598 without diabetes). Depression and anxiety were assessed using the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale, respectively.The prevalence of depression and anxiety symptoms were 61% and 45%, in people with diabetes (PWD) and 62% and 44%, respectively, in people without diabetes. PWD who have had their diabetes visit canceled by the clinic were more likely to report depression and anxiety symptoms than those without diabetes (odds ratio [95% confidence interval]: 1.37 [1.02, 1.84] and 1.37 [1.04, 1.80], for depression and anxiety; respectively). PWD who had no method of telecommunication with their health care providers (HCP) during the pandemic, PWD with A1C of ≥ 10%, women, employees (particularly HCPs), students, unmarried individuals, and those with lower income were more likely to report depression and/or anxiety symptoms (all P 0.01). Fear of acquiring the coronavirus infection; running out of diabetes medications; or requiring hospitalization for hypoglycemia, hyperglycemia, or diabetic ketoacidosis; and lack of telecommunication with HCPs were all associated with significantly higher odds of having depression and anxiety symptoms among PWD.The remarkably high prevalence of depression and anxiety symptoms during the COVID-19 pandemic, particularly among subgroups of PWD, calls for urgent public health policies to address mental health during the pandemic and reestablish health care access for PWD.目的: 明确2019年新型冠状病毒肺炎暴发期间糖尿病患者和非糖尿病者抑郁和焦虑的患病率及其相关因素。 方法: 这是一项基于横断面的问卷研究, 收集了居住在阿拉伯海湾地区的2166名受试者(568名糖尿病患者, 1598名非糖尿病者)的人口统计学和心理健康数据。抑郁和焦虑分别用9个条目的健康问卷和7个条目的广泛性焦虑量表进行评估。 结果: 糖尿病组抑郁和焦虑症状的发生率分别为61%和45%, 非糖尿病组分别为62%和44%。被门诊取消就诊的糖尿病患者比无糖尿病的患者更容易出现抑郁和焦虑症状(抑郁和焦虑的优势比[95%可信区间]分别为1.37[1.02, 1.84]和1.37[1.04, 1.80])。糖尿病患者中无法联系医疗服务提供者(HCP)的残疾人, A1C≥10%的残疾人, 女性, 从业人员(尤其是HCP), 学生, 未婚人士和低收入人群更易出现抑郁和/或焦虑症状(P0.0 1)。糖尿病患者中担心感染病毒; 糖尿病药物用完; 或因低血糖, 高血糖或糖尿病酮症酸中毒而需要住院; 缺乏与HCP的通讯, 这些都与出现抑郁和焦虑症状的几率显著增加有关。 结论: 新型冠状病毒肺炎大流行期间抑郁和焦虑症状的患病率非常高, 特别是在糖尿病患者亚群中, 迫切需要公共卫生政策来解决大流行期间的心理健康问题, 并重新建立糖尿病患者的卫生保健服务。.

Background: Bariatric or weight loss surgery provides the most substantial and sustainable weight loss in individuals with obesity. Caloric restriction and malabsorption are not the only mechanisms by which bariatric surgery reduces body weight and improves glycemic control. Alterations in the secretion and activity of hormones are also the contributory mechanisms in bariatric surgery. We evaluated the levels of retinol binding protein 4 (RBP4) and adipsin after gastric sleeve surgery and their relationship with insulin and lipid parameters. Method: Thirty-three obese (BMI > 38.3) healthy male subjects age ranged from 25 to 50 years were selected for this study. Plasma levels of RBP4 and adipsin were analyzed before and six months after gastric sleeve surgery by ELISA, along with plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid profile. Results: Circulating RBP4 was not significantly changed by bariatric surgery (4382.85±7.03 ng before, and 4393.28±5.769 ng after surgery, P= 0.842), neither did adipsin (2949.68±8.16 pg before, and 2917.90±7.295 pg after surgery, P=0.535). As expected, there was a reduction in BMI, insulin levels and HOMA-IR after six months of surgery. Lipid profile analysis revealed that cholesterol, high density lipoproteins (HDL), and low density lipoproteins (LDL) levels were increased after surgery (4.26±0.027 to 5.12±0.026 mmol/L and 0.90±0.007 to 1.55±0.011 mmol/L and 2.62±0.02 to 2.98±0.022 mmol/L, P Conclusions: Our findings do not suggest a role for RBP4 and adipsin in the improvement of insulin sensitivity in obese male population after gastric sleeve surgery. Moreover, there was no correlation between their plasma levels and either BMI, glucose, insulin, or lipid profiles. Disclosure S. Alshubrami: None. M. Iqbal: None. A. Alfadda: None. K. Alregaiey: None. Funding King Abdulaziz City for Science and Technology (1-17-03-001-0026)

BACKGROUND Clinical and radiographic status around short dental implants in patients with different glycemic levels remains unexplored. PURPOSE To determine the clinical and radiographic bone level (RBL) around short dental implants in type-2 diabetes mellitus (T2DM), prediabetic, and non-diabetic patients. MATERIALS AND METHODS Participants were grouped into three groups based on HbA1c levels: T2DM (Group-1); prediabetic patients (Group-2); and non-diabetic subjects (Group-3). Clinical recordings included the assessment of peri-implant plaque index (PI), bleeding on probing (BOP), probing depth (PD). Radiographic analysis included evaluation of standardized periapical digital radiographs using specialized software and image analyzer. RESULTS Clinical peri-implant parameters including PI and BOP were statistically significantly higher in group-1 (P

Background: Bladder cancer is a life-threatening disease and a major cause of cancer-associated complications. The main challenges confronted during the clinical management of bladder cancer are associated with recurrence and disease progression to the muscle-invasive phenotype. Improved early detection of the disease is of paramount importance to prevent disease progression and improve survival. Hence, novel clinically applicable biomarkers for early detection are warranted. Methods: In the current study, a comparative proteomic approach was undertaken using plasma samples to identify protein biomarkers associated with the muscle-invasive phenotype of bladder carcinoma. Isolated plasma proteins were depleted, DIGE-labeled, then subjected to conventional 2D electrophoresis followed by mass spectrometry for identification of differentially expressed proteins. Western blot was used for data validation. Results: Fourteen differentially expressed proteins with statistically significant changes in abundance between the cancer group and control group were identified. Three differentially expressed proteins were selected for validation, among which apolipoprotein A1 exhibited high specificity and sensitivity (AUC = 0.906). Ingenuity pathway analysis identified IFN-γ and TNF-α as the main signaling hub for the differentially regulated proteins. Conclusion: Our findings provide additional insight into understanding bladder cancer pathogenesis. Our data identified potential non-invasive plasma-derived biomarker proteins that merit additional investigation to validate its clinical usefulness to prevent bladder cancer progression.

Hepatic hydrothorax (HH) is a transudative pleural effusion that complicates advanced liver cirrhosis. Cases refractory to medical treatment in the form of salt restriction and diuretics are labeled refractory hepatic hydrothorax (RHH) and may require transjugular intrahepatic portosystemic shunts (TIPSS) or even liver transplantation. Renal impairment is common in advanced liver disease, worsens its prognosis, and makes the management of HH more challenging. Successful antiviral therapy reduces some of the complications of cirrhosis secondary to hepatitis C virus (HCV) infection. We herein report two cirrhotic patients with chronic kidney disease who developed RHH which resolved after the successful treatment of their HCV infection with direct-acting antivirals (DAAs). In cases of RHH associated with HCV cirrhosis, a trial of DAAs is warranted before resorting to TIPSs or liver transplantation.

The identification of clinically-relevant early diagnostic and prognostic protein biomarkers is essential to maximize therapeutic efficacy and prevent cancer progression. The aim of the current study is to determine whether aberrant plasma protein profile can be applied as a surrogate tool for early diagnosis of bladder carcinoma. Plasma samples from patients with low grade non-muscle invasive bladder cancer and healthy controls were analyzed using combined 2D-DIGE and mass-spectrometry to identify differentially expressed proteins. Validation was performed using western blotting analysis in an independent cohort of cancer patients and controls. Fifteen differentially-expressed proteins were identified of which 12 were significantly up-regulated and three were significantly down-regulated in tumors compared to controls. The Ingenuity Pathways Analysis revealed functional connection between the differentially-expressed proteins and immunological disease, inflammatory disease and cancer mediated through chemokine and cytokine signaling pathway and NF-kB transcription factor. Among the three validated proteins, haptoglobin was able to distinguish between patients with low grade bladder cancer and the controls with high sensitivity and specificity (AUC > 0.87). In conclusion, several biomarker proteins were identified in bladder cancer. Haptoglobin is a potential candidate that merit further investigation to validate its usefulness and functional significance as potential biomarkers for early detection of bladder cancer.

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is a coenzyme encoded by ACADVL that converts very-long-chain fatty acids into energy. This process is disrupted by c.65C > A; p.Ser22∗ mutation. To clarify mechanisms by which this mutation leads to VLCAD deficiency, we evaluated differences in molecular and cellular functions between mesenchymal stem cells with normal and mutant VLCAD. Saudi Arabia have a high incidence of this form of mutation. Stem cells with mutant VLCAD were isolated from skin of two patients. Metabolic activity and proliferation were evaluated. The Same evaluation was repeated on normal stem cells introduced with same mutation by CRISPR. Mitochondrial depiction was done by electron microscope and proteomic analysis was done on patients’ cells. Metabolic activity and proliferation were significantly lower in patients’ cells. Introducing the same mutation into normal stem cells resulted in the same defects. We detected mitochondrial abnormalities by electron microscopy in addition to poor wound healing and migration processes in mutant cells. Furthermore, in a proteomic analysis, we identified several upregulated or downregulated proteins related to hypoglycemia, liver disorder, and cardiac and muscle involvement. We concluded experimental assays of mutant ACADVL (c.65C > A; p.Ser22∗) contribute to severe neonatal disorders with hypoglycemia, liver disorder, and cardiac and muscle involvement.

Metabolic dysfunction associated with obesity threatens to inundate health care resources by increasing the incidences of obesity-related diseases. The aim of the present study was to investigate the changes in the urinary proteome of 18 individuals classified into metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) patients. Proteome analysis was performed using the two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Upon analysis, a total of 54 proteins were found to be affected with &ge, 1.5-fold change (ANOVA, p &le, 0.05), of which 44 proteins were upregulated and 10 proteins were downregulated. These differentially abundant proteins were related to nuclear factor &kappa, B (NF-&kappa, B) and p38 mitogen-activated protein (MAP) kinase pathways and were involved in cellular compromise, inflammatory response, and cancer. Proteins involved in inflammation (fibrinogen alpha (FIBA), serotransferrin (TRFE, and kininogen-1 (KNG1)) and insulin resistance (ADP-ribosylation factor (ARF)-like protein 15 (ARL15) and retinol-binding protein 4 (RET4)) were found to be significantly increased in the urine samples of MUHO compared to MHO patients. Investigating the effects of obesity on urinary proteins can help in developing efficient diagnostic procedures for early detection and prevention of obesity-related complications.

Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP is an epigenetic regulator of thermogenesis and obesity. In mouse subcutaneous adipocytes, TonEBP expression increases > 50-fold in response to high-fat diet (HFD) feeding. Mice with TonEBP haplo-deficiency or adipocyte-specific TonEBP deficiency are resistant to HFD-induced obesity and metabolic defects (hyperglycemia, hyperlipidemia, and hyperinsulinemia). They also display increased oxygen consumption, resistance to hypothermia, and beiging of subcutaneous fat tissues. TonEBP suppresses the promoter of β3-adrenoreceptor gene, a critical regulator of lipolysis and thermogenesis, in ex vivo and cultured adipocytes. This involves recruitment of DNMT1 DNA methylase and methylation of the promoter. In human subcutaneous adipocytes TonEBP expression displays a correlation with body mass index but an inverse correlation with β3-adrenoreceptor expression. Thus, TonEBP is an attractive therapeutic target for obesity, insulin resistance, and hyperlipidemia., Activation of thermogenic beige adipocytes within white adipose tissue increases energy expenditure. Here, the authors show that expression of TonEBP in adipocytes is increased when mice are fed a high fat diet and that it suppresses expression of beta3-adrenoreceptor.

Objective: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. Methods: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence Results: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults. These included strong recommendations in support of lifestyle interventions rather than usual care alone, individualized counseling interventions rather than generic educational pamphlets, physical activity rather than no physical activity, and physical activity in addition to diet rather than diet alone. Metformin and orlistat were suggested as conditional recommendations for the management of overweight and obesity in adults. Bariatric surgery was recommended, conditionally, for the management of obese adults (body mass index of ≥40 or ≥35 kg/m 2 with comorbidities). Conclusions: The current guideline includes recommendation for the non-pharmacological, pharmacological, and surgical management of overweight and obese adults. In addition, the panel recommends conducting research priorities regarding lifestyle interventions and economic analysis of drug therapy within the Saudi context, as well as long term benefits and harms of bariatric surgery. Saudi Med J 2016; Vol. 37 (10): 1151-1162 doi: 10.15537/smj.2016.10.14353 How to cite this article: Alfadda AA, Al-Dhwayan MM, Alharbi AA, Al Khudhair BK, Al Nozha OM, Al-Qahtani NM, Alzahrani SH, Bardisi WM, Sallam RM, Riva JJ, Brozek JL, Schunemann HJ, Moore A. The Saudi clinical practice guideline for the management of overweight and obesity in adults. Saudi Med J . 2016 Oct;37(10):1151-62. doi: 10.15537/smj.2016.10.14353.

Objectives: To determine seasonal variations in the vitamin D status of Saudi adolescent girls in Riyadh, Kingdom of Saudi Arabia (KSA) and its effect in biochemical and clinical characteristics. Methods: In this prospective study, a total of 2000 Saudi females aged 12-18 years from different schools in Riyadh, KSA participated and submitted a generalized questionnaire with clinical information. Fasting blood samples were obtained in 1618 subjects for the winter season (December to February) and only 499 subjects returned to submit fasting blood samples for the summer season (June-August). Circulating serum 25(OH)D, parathyroid hormone (PTH), and other biomarkers of bone remodeling were measured during both seasons. Results: Vitamin D deficiency (serum 25(OH)D less than 25 nmol/L) was significantly higher during summer than winter (63.5% versus 40.8%; p less than 0.001). Mean serum PTH was also significantly higher during summer than winter ( p less than 0.01). In all subjects, serum PTH showed a significant inverse association with 25(OH)D at levels below 40 nmol/L (r=-0.21; p less than 0.001). The prevalence of subjects having clinical and metabolic manifestations suggestive of osteomalacia was 2.13% (N=33 out of 1548). Conclusion: Seasonal variations in the vitamin D status of Saudi adolescent females significantly modifies biochemical parameters as response to vitamin D status change. In the meantime, heightened public health awareness should be given to populations at higher risk for vitamin D deficiency. Saudi Med J 2016; Vol. 37 (9): 1002-1008 doi: 10.15537/smj.2016.9.15248 How to cite this article: Sulimani RA, Mohammed AG, Alfadda AA, Alshehri SN, Al-Othman AM, Al-Daghri NM, Hanley DA, Khan AA. Vitamin D deficiency and biochemical variations among urban Saudi adolescent girls according to season. Saudi Med J 2016; 37(9): 1002-1008. doi: 10.15537/smj.2016.9.15248.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic condition caused by the accumulation of fat in the liver. NAFLD may range from simple steatosis to advanced cirrhosis, and affects more than 1 billion people around the world. To date, there has been no effective treatment for NAFLD. In this study, we evaluated the expression of 4 candidate NAFLD biomarkers to assess their possible applicability in the classification and treatment of the disease. Twenty-six obese subjects, who underwent bariatric surgery, were recruited and their liver biopsies obtained. Expression of 4 candidate biomarker genes, PNPLA3, COL1A1, PPP1R3B, and KLF6 were evaluated at gene and protein levels by RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. A significant increase in the levels of COL1A1 protein (P = .03) and PNPLA3 protein (P = .03) were observed in patients with fibrosis-stage NAFLD compared to that in patients with steatosis-stage NAFLD. However, no significant differences were found in abundance of PPP1R3B and KLF6 proteins or at the gene level for any of the candidate. This is the first study, to our knowledge, to report on the expression levels of candidate biomarker genes for NAFLD in the Saudi population. Although PNPLA3 and PPP1R3B had been previously suggested as biomarkers for steatosis and KLF6 as a possible marker for the fibrosis stage of NAFLD, our results did not support these findings. However, other studies that had linked PNPLA3 to fibrosis in advanced NAFLD supported our current finding of high PNPLA3 protein in patients with fibrosis. Additionally, our results support COL1A1 protein as a potential biomarker for the fibrosis stage of NAFLD, and indicate its use in the screening of patients with NAFLD. Further studies are required to validate the use of COL1A1 as a biomarker for advanced NAFLD in a larger cohort.

The small intestine is one of the most ischemia-sensitive organs used in transplantation. To better preserve the intestinal graft viability and decrease ischemia-reperfusion injury, a device for extracorporeal perfusion was developed. We present the results for the first series of perfused human intestine with an intestinal perfusion unit (IPU). Five human intestines were procured for the protocol. (1) An experimental segment was perfused by the IPU delivering cold preservation solution to the vascular and luminal side continually at 4 oC for 8 h. (2) Control (jejunum and ileum) segments were preserved in static cold preservation. Tissue samples were obtained for histopathologic grading according to the Park/Chiu scoring system (0 = normal, 8 = transmural infarction). Jejunal experimental segments scored 2.2 with the Park/Chiu system compared to the control segments, which averaged 3.2. Overall scoring for ileum experimental and control segments was equal with 1.6. This data presents proof of concept that extracorporeal intestinal perfusion is feasible. The evidence shows that the IPU can preserve the viability of human intestine, and histopathologic evaluation of perfused intestine is favorable. Our early results can eventually lead to expanding the possibilities of intestinal preservation.

This study examined the effects of weekly 35,000 IU vitamin D supplementation for 4 weeks on bone turnover markers (BTMs). There was improvement in the levels of parathyroid hormone (PTH), osteocalcin, and carboxy-terminal telopeptides of crosslinks of type 1 collagen (βCTX) which paralleled the increase in vitamin D levels. The effects of vitamin D supplementation on bone turnover markers (BTMs) have been inconsistent. This study examined the effects of weekly 35,000 IU vitamin D supplementation for 1 month on BTMs. Sixty-eight vitamin D deficient adolescent females were given 35,000 IU of vitamin D3 for 4 weeks. Pre and post intervention blood samples were taken for 25(OH) D, PTH, osteocalcin and βCTX. There was a significant increase in serum 25 (OH) D in the post intervention period which was accompanied by a significant decrease in PTH, osteocalcin and βCTX (P

Objectives: This study evaluated the effect of a cash reward program on promoting weight loss and whether this effect will last after 1 year of follow-up. Materials and Methods: This is a retrospective analysis of a 4-month program that provides cash reward for losing weight. The study individuals were weight loss program participants, aged 18–65 years, reached after 1 year (n = 162). Participants were categorized according to their main reason for joining the program as follows: those for whom incentive was the primary reason to enroll (incentive-motivated) and those who participated mainly to lose weight regardless of the incentive (self-motivated). Results: There was a significant weight loss in all participants at the end of the 4-month program compared with that at baseline (89.49 ± 18.86 vs. 96.09 ± 20.38 kg,P < 0.001). Approximately 58% of all participants lost ≥5% of their initial body weight, and almost 55% remained above this threshold at 1 year. The incentive-motivated group lost more weight than the self-motivated group at the end of the program but did not lose any further weight, whereas the self-motivated group continued to lose weight. After 1 year, both groups had achieved the same weight loss. Conclusions: The cash reward program was effective in inducing short-term weight loss. The optimal duration for financial incentive-based programs in inducing a sustainable weight loss and their cost-effectiveness are important questions for further investigation.

Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood. In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, p ≤ 0.05) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the NFκB, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.

Childhood obesity is a matter of great concern for public health. Efforts have been made to understand its impact on health through advanced imaging techniques. An increasing number of studies focus on fat distribution and its associations with metabolic risk, in interaction with genetics, environment and ethnicity, in children. The present review is a qualitative synthesis of the existing literature on visceral and subcutaneous abdominal, intrahepatic and intramuscular fat. Our search revealed 80 original articles. Abdominal as well as ectopic fat depots are prevalent already in childhood and contribute to abnormal metabolic parameters, starting early in life. Visceral, hepatic and intramuscular fat seem to be interrelated but their patterns as well as their independent contribution on metabolic risk are not clear. Some ethnic-specific characteristics are also prevalent. These results encourage further research in childhood obesity by using imaging techniques such as magnetic resonance imaging and computed tomography. These imaging methods can provide a better understanding of fat distribution and its relationships with metabolic risk, compared to less detailed fat and obesity assessment. However, studies on bigger samples and with a prospective character are warranted.

Background: Primary eosinophilic gastrointestinal disorders, a spectrum of inflammatory conditions, occurs when eosinophils selectively infiltrate the gut in the absence of known causes for such tissue eosinophilia. These may be classified into eosinophilic esophagitis, eosinophilic gastroenteritis and eosinophilic colitis (EC). This review focuses on EC: its pathogenesis, epidemiology, clinical presentation, diagnosis and current approach to treatment. Sources of data: A literature review published in English was performed using Pubmed, Ovid, Google scholar search engines with the following keywords: eosinophilic gastrointestinal disorder, EC, eosinophils, colitis and gastrointestinal. Areas of agreement: The basis for primary EC appears related to increased sensitivity to allergens, principally as a food allergy in infants and a T lymphocyte-mediated event in adults. Endoscopic changes are generally modest, featuring edema and patchy granularity. Areas of controversy: Clear clinical and pathological diagnostic criteria of EC and its management strategy. Growing points: Intestinal involvement of EC is primarily mucosal, presenting as a mild self-limited proctitis in infants and self-limited colitis in young adults. Therapeutic approaches based on case reports tend to use either elimination diets to avoid a presumed allergen; agents traditionally used in inflammatory disease or targeted drugs like anti-histamines or leukotriene receptor antagonists. Areas timely for developing research: Prospective randomized controlled trials addressing the disease natural history, possible preventive methods and effective medical approach and long-term prognosis are required.

Primary eosinophilic gastrointestinal disorders (EGIDs) represent a spectrum of inflammatory gastrointestinal disorders in which eosinophils infiltrate the gut in the absence of known causes for such tissue eosinophilia. EGIDs can be subgrouped as eosinophilic esophagitis (EE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC). The least frequent manifestation of EGIDs is EC. EC is a heterogeneous entity with a bimodal age distribution, presenting with either an acute self-limited bloody diarrhea in otherwise healthy infants or as a more chronic relapsing colitis in young adults. The pathophysiology of primary EC appears related to altered hypersensitivity, principally as a food allergy in infants and T lymphocyte-mediated (i.e. non-IgE associated) in young adults. In adults, symptoms include diarrhea, abdominal pain, and weight loss. Endoscopic changes are generally modest, featuring edema and patchy granularity. Although standardized criteria are not yet established, the diagnosis of EC depends on histopathology that identifies an excess of eosinophils. Therapeutic approaches are based on case reports and small case series, as prospective randomized controlled trials are lacking. Eosinophilic colitis in infants is a rather benign, frequently food-related entity and dietary elimination of the aggressor often resolves the disorder within days. Adolescent or older patients require more aggressive medical management including: glucocorticoids, anti-histamines, leukotriene receptors antagonists as well as novel approaches employing biologics that target interleukin-5 (IL-5) and IgE. This review article summarizes the current knowledge of EC, its epidemiology, clinical manifestations, diagnosis, and treatment.

ObjectiveStudies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2).Design and methodsOne hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR.ResultsCirculating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (PP=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01).ConclusionObesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.

Orosomucoid (ORM), also called alpha-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-alpha, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-kappaB and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-alpha-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction.

The aim of the study was to determine surgical indication and complication of subtotal thyroidectomy in patients being treated for Graves' disease at King Khalid University Hospital Riyadh Saudi Arabia in the period between January 1996 and December 2005. Twenty-five out of 194 adult patients with Graves' disease had thyroidectomy for hyperthyroidism during the 10-year period representing 13% comprising 11 males and 14 females. Mean age at presentation for all the patients was 28±12 years. Males had higher serum T4 77.7±20.7 than females 49.8±21.9 pmol L-1; p

Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases., The hormone adiponectin is produced by fat cells and has positive metabolic effects. Here, Kim et al. show that DNA methyltransferase 1 (DNMT1) represses adiponectin expression through hypermethylation of its promoter, and that inflammatory cytokines enhance DNMT1 activity in obese mice and humans.

This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects, Age 24.4 ± 7.9 year, body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year, BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year, BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12–14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p &lt, 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values &lt, 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.

Few studies have been reported from the Kingdom of Saudi Arabia (SA) to describe the clinical presentation and long term outcomes of subacute thyroiditis (SAT). Our aim was to review the demographic, anthropometric, clinical presentation, laboratory results, treatment, and disease outcome in Riyadh region and to compare those with results from different regions of the Kingdom and different parts of the world. We reviewed the medical files of patients who underwent thyroid uptake scan during an 8-year period in King Khalid University Hospital. Only 25 patients had confirmed diagnosis of thyroiditis. Age and gender distribution were similar to other studies. Most patients presented with palpitation, goiter, and weight change. Elevated thyroid hormones, suppressed thyroid-stimulating hormone, and elevated ESR were reported. Among those, 7 cases of SAT were recorded.β-Blockers were prescribed to 57% and nonsteroidal anti-inflammatory drugs to 29% of SAT. Long follow-up demonstrated that 85.7% of SAT cases recovered, while 14.3% developed permanent hypothyroidism. In conclusion, SAT is uncommon in the central region of SA. Compared to the western region, corticosteroid is not commonly prescribed, and permanent hypothyroidism is not uncommon. A nation-wide epidemiological study to explain these interprovincial differences is warranted.

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet ( n = 5) and one undergoing bariatric surgery ( n = 7), used both targeted and untargeted proteomic approaches to determine changes in protein levels pre- and post-intervention (i.e. 3–6 months later). Changes were observed in both circulating and excreted proteins following weight loss. Targeted multiplexed biochip arrays measured 12 plasma peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin, interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C-reactive protein. Following a low-calorie diet, plasma insulin and C-reactive protein levels were significantly reduced ( P = 0.045 and P = 0.030, respectively); adiponectin increased and leptin decreased following surgery ( P = 0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D difference in-gel electrophoresis (DIGE) showed 28 protein spots with ≥1.5-fold changes in expression following weight loss by a low-calorie diet; comparison of pre- and post-intervention urine samples from the bariatric surgery group showed changes in excretion of 110 protein spots. The combination of targeted protein analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery) proteomic assessment of hundreds of proteins offers valuable insights into the mechanistic differences between alternative weight-loss strategies. This is a powerful hypothesis-generating approach to study complex, multifactorial syndromes such as obesity. The findings that arise from these studies can then be validated in targeted, hypothesis-directed investigations.

It is now well established that not all obese subjects are at increased risk of cardiometabolic complications; such patients are termed the metabolically healthy obese. Despite their higher-than-normal body fat mass, they are still insulin sensitive, with a favorable inflammatory and lipid profile and no signs of hypertension. It remains unclear which factors determine an individual's metabolic health. Adipose tissue is known to secrete multiple bioactive substances, called adipokines, that can contribute to the development of obesity-associated complications. The goal of this study was to determine whether the circulating adipokine profiles differs between metabolically healthy and metabolically unhealthy overweight and obese subjects, thereby obtaining data that could help to explain the link between obesity and its related cardiometabolic complications. We defined metabolic health in terms of several metabolic and inflammatory risk factors. The serum adiponectin levels were higher in the healthy group and showed a positive correlation with HDL cholesterol levels in the unhealthy group. There were no differences between the two groups in the levels of serum leptin, chemerin and orosomucoid. Accordingly, adiponectin might play a role in protecting against obesity-associated cardiometabolic derangements. More studies are needed to clarify the role of different chemerin isoforms in this system.

Aim Eosinophilic colitis (EC) is a rare manifestation of eosinophilic gastrointestinal disorders. Due to its rarity, little information is available on its natural history. Method From the single population-based pathology database of the Calgary Health Region (comprising a population of 1.28 million in 2008), cases of EC during the period 1996–2008 were identified. Medical records of all adults diagnosed with EC were identified and the pathology reviewed. The patients were then contacted for follow-up using a standardized questionnaire. Results Seven cases of EC (four in women) were identified, with a median follow-up of 45 (23–79) months. The median age at diagnosis was 42 (22–70) years. Symptoms at diagnosis were abdominal pain (86%), nonbloody diarrhoea (57%), bloody diarrhoea (29%) and significant (>10%) weight loss (29%). Three patients gave a history of allergic reactions to drugs and four reported allergy to cows' milk. Endoscopic findings were nonspecific, ranging from oedema to small aphthous ulceration. An eosinophilic infiltrate was identified in the lamina propria in the initial colonic biopsy in all patients. Over the longer term, three patients experienced spontaneous resolution without treatment. Two continued to have mild diarrhoea and abdominal cramps but did not require medical therapy. Two patients required medical treatment by 5-aminosalicylic acid, with one requiring prednisone and azathioprine maintenance therapy. Conclusion Eosinophilic colitis is a rare mostly self-limiting disease affecting middle-aged adults. It usually has a mild clinical course and drug treatment is not usually necessary. When required, drug treatment follows the standard medication for other inflammatory bowel disease.

Obesity and aging are interrelated conditions that both cause changes in adipocyte metabolism and affect the distribution of fat in both subcutaneous and visceral depots. In addition, both weight gain and aging can lead to similar clinical outcomes such as insulin resistance, cardiovascular disease, type 2 diabetes mellitus, atherosclerosis and stroke. Our objective was to examine the changes in protein expression within the subcutaneous adipose tissue of obese patients, matched for BMI, in relation to age. Mature adipocytes were isolated from liposuction samples of abdominal subcutaneous adipose tissue collected from both young (26.2±4.3 (mean age±SD); n=7) and old (52.2±4.7 (mean age±SD); n=7) obese individuals. Total protein extracts were then compared by two-dimensional difference in gel electrophoresis (2D DIGE). Thirty differentially expressed protein spots (ANOVA test, p≤0.05; fold-change ≥1.8) were detected, of which, 15 were identified by MALDI-TOF mass spectrometry. These were comprised of a total of thirteen unique protein sequences. Nine proteins were more abundant in the adipocytes isolated from old vs. young individuals. These proteins included prohibitin 1, protein disulphide isomerase A3, beta actin, profilin, aldo-ketoreductase 1 C2, alpha crystallin B and the annexins A1, A5 and A6. Four other proteins were less abundant in the adipocytes from old, obese subjects and these included keratin type 2 cytoskeletal 1, keratin type 2 cytoskeletal 10 and hemoglobins A and B. The differentially abundant proteins were investigated by Ingenuity Pathway Analysis (IPA) to reveal their associations with known biological functions. This analysis identified signal transducer and activator of transcription 3 as the central molecule in the connectivity map and the apoptotic pathway as the pathway with the highest score. Differences in the abundances of several proteins were confirmed by immunoblotting: i.e., prohibitin 1, protein disulphide isomerase A3, beta actin, profilin and signal transducer and activator of transcription 3 proteins. In conclusion, proteomic analysis of subcutaneous adipose tissue reveals differences in the abundance of proteins in adipocytes isolated from young vs. old individuals. These differentially abundant proteins are involved in the regulation of apoptosis, cellular senescence and inflammatory response. All these are common pathologic events in both obesity and aging.

Studies have demonstrated that total osteocalcin (TOC) is associated with metabolic syndrome (MetS) and therefore might influence the risk of cardiovascular disease in humans. Undercarboxylated osteocalcin (uOC) regulates insulin secretion and sensitivity in mice, but its relation to MetS in humans is unclear. We aimed to determine whether uOC is related to MetS and/or its individual components and other cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM), and whether TOC and uOC have utility in predicting the cardiovascular risk. We studied 203 T2DM patients with and without MetS. MetS was defined based on the NCEP-ATP III criteria. A correlation analysis was performed between the three outcome variables: (i) TOC, (ii) uOC, and (iii) carboxylated osteocalcin (cOC) and MetS components and other cardiovascular risk factors. Both TOC and uOC were significantly lower in patients with MetS compared to those without MetS, independent of body mass index. In patients with MetS, uOC was significantly and positively correlated with HDL cholesterol, while TOC was significantly and negatively correlated with serum triglycerides. We report for the first time that uOC is related to lipid indices in patients with T2DM. Further studies are necessary to determine whether uOC can be utilized for cardiovascular risk assessments in these patients.