Prevalence of type 2 diabetes (T2D) in Lebanon: association with inflammatory and infectious clinical markers.

BACKGROUND: Diabetes is a growing health concern in the Middle East, particularly in countries with high rates of obesity and unhealthy lifestyles. Therefore, this study aimed to determine the prevalence of type 2 diabetes (T2D) in Lebanon and its association with clinical markers of inflammation and infection. METHODS: This cross-sectional study examined retrospectively the medical laboratory record of 4093 patients from all Lebanese regions. Prevalence of T2D and its association with age, gender, calcium, vitamin D (VitD), neutrophils-to-lymphocytes ratio (NLR), and C-reactive protein (CRP) were determined. The prevalence of infection in a subpopulation of 712 patients tested from blood, body fluid, sputum, swab, tissue, and urine samples and its etiology was also assessed. RESULTS: Overall, 17% (n = 690) of our participants had T2D, and the mean HbA1c was 5.9% ± 1.2. Age, gender, triglycerides, NLR, and calcemia were significantly associated with T2D. The prevalence of infections in a subgroup of 712 patients was 11.1% (n = 79). Urinary tract infections (UTIs) caused by Escherichia coli (E. coli) were the most common cause of infection, with the highest prevalence in the pre-diabetic group. Serum CRP level was significantly higher in the diabetic group than the pre-diabetic and control groups. Diabetic patients also presented a significantly higher percentage of NLR > 3 compared to the pre-diabetic and control groups. CONCLUSION: The prevalence of T2D is increasing in the Lebanese population compared to prior reports. These results should be considered to guide effective public health preventive strategies.

Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children.

Background Growing evidence reports an association between inflammatory markers, obesity and blood pressure (BP). Specifically, the intergenic single nucleotide polymorphism (SNP) rs7556897T > C (MAF = 0.34) located between SLC19A3 and the CCL20 was shown to be associated with chronic inflammatory diseases. In addition, CCL20 expression was found increased in pancreatic islets of obese rodents and human pancreatic ß cells under the influence of inflammation. In this study, we hypothesized that SNP rs7556897 could affect BP levels, thus providing a link between inflammation, BP and obesity. Methods BP was measured under supine position with a manual sphygmomanometer; values reported were the means of three readings. We analyzed rs7556897 in 577 normal weight and 689 obese French children. Using real-time polymerase chain reaction (PCR), we quantified CCL20 and SLC19A3 expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) of normal weight and overweight children. Results The rs7556897C allele was negatively associated with diastolic BP in normal weight children (ß = -0.012 ± 0.004, p = 0.006) but positively associated in obese children (ß = 2.178 ± 0.71, p = 0.002). A significant interaction between rs7556897T > C and the obesity status (obese or normal weight) was detected (ß = 3.49, p = 9.79 × 10-5) for BP in a combined population analysis. CCL20 mRNA was only expressed in the adipose tissue of overweight children, and its expression levels were 10.7× higher in PBMCs of overweight children than normal weight children. Finally, CCL20 mRNA levels were positively associated with rs7556897T > C in PBMCs of 58 normal weight children (ß = 0.43, p = 0.002). SLC19A3 was not expressed in PBMCs, and in adipose tissue, it showed same levels of expression in normal weight and overweight children. The gene expression results may highlight a specific involvement of CCL20 via communicating obesity/inflammation pathways that regulate BP. Conclusions Childhood obesity reverses the effect of rs7556897T > C on diastolic BP, possibly via the modulation of CCL20 expression levels.

Adiponectin and its globular fragment differentially modulate the oxidative burst of primary human phagocytes.

Adiponectin (Acrp30) belongs to the family of C1q/tumor necrosis factor α (TNFα)-related proteins. Acrp30 circulates as multimers of high, middle, and low molecular weight. In this study, we detected Acrp30 and its globular fragment (gAcrp30) in synovial fluid from rheumatoid arthritis patients. Intriguingly, the LMW form was more abundant in synovial fluid than in serum from both rheumatoid arthritis patients and healthy subjects. We also investigated the effects of Acrp30 and gAcrp30 on reactive oxygen species (ROS) production via the phagocytic NADPH oxidase. Acrp30 inhibited fMLF-induced ROS production by human phagocytes, whereas gAcrp30 enhanced it. gAcrp30's effect is additive with TNFα, whereas Acrp30 inhibited TNFα-induced priming. gAcrp30 enhanced NOX-2 expression at the plasma membrane, with a concomitant increase in p47(phox) phosphorylation. Selective inhibitors of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1 (ERK1)/2 abrogated p47(phox) phosphorylation by gAcrp30. In contrast, p47(phox) phosphorylation was inhibited by Acrp30 in association with increased AMP-activated protein kinase (AMPK) phosphorylation in phagocytes. These results suggest that human phagocyte ROS production is regulated by different mechanisms selective for Acrp30 versus gAcrp30. An imbalance between gAcrp30 and higher molecular weight isoforms of Acrp30 might contribute to chronic inflammation by regulating NADPH oxidase.

The association of vascular endothelial growth factor related SNPs and circulating iron levels might depend on body mass index.

BACKGROUND AND OBJECTIVES: Vascular Endothelial Growth Factor (VEGF) is an essential regulator of vascular biology. In addition to the well-established role in angiogenesis, circulating VEGF levels were found elevated in severely anemic patients, pointing out that anemia might affect the progression of angiogenesis in malignant and benign diseases through the alteration of VEGF levels. Ten single nucleotide polymorphisms (SNPs) in VEGFA and other loci were shown to explain more than 50% of its circulating levels. This study investigated the association of those ten VEGF-related SNPs with serum iron levels in a general Lebanese population free of chronic diseases (N = 460). RESULT: We found that the rs10738760 and the body mass index (BMI) were associated with decreased Iron levels (p = 0.002, and p < 0.001, respectively). When taken together, both variables, rs10738760 and BMI, interacted to reduce iron levels (p < 0.001). According to obesity status, the stratification revealed that the effect of rs10738760 was more pronounced in obese than non-obese individuals (p = 0.025). Conclusion: The intergenic SNP rs10738760 is associated with circulating iron levels, and this association depends on BMI status. Although of interest, these results need replication in larger populations from different ancestries.

Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK.

Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.

The Association of rs1898830 in Toll-Like Receptor 2 with Lipids and Blood Pressure.

BACKGROUND AND OBJECTIVE: Toll-like receptors (TLRs) are important components of the innate immune system, involved in establishing immunity to infections. Apart from being implicated in immunity, numerous studies have reported that many TLRs, including TLR2, are involved in the pathogenesis of cardiovascular diseases and their risk factors. Since rs1898830 is associated with TLR2-mediated cellular activation, we aimed to study its association with CVD risk factors, such as lipid levels and hypertension. METHODS: A cross-sectional study was conducted on 460 individuals free from chronic diseases. Clinical and biological data were collected and DNA was extracted and genotyped using Kompetitive allele specific PCR (KASP™). Multiple logistic regression models, adjusted for six covariates, were used. A power calculation analysis was also performed. RESULTS: We found that rs1898830 in TLR2 was positively associated with hypertension (OR = 2.18, p = 0.03) and negatively associated with high-density lipoprotein cholesterol (OR = 0.66, p = 0.05). In contrast, no relation was found with total cholesterol and low-density lipoprotein cholesterol. CONCLUSION: The present results provide additional evidence supporting the implication of TLR2 in CVD risk factors.

Increased risk of hypercholesterolemia in a French and Lebanese population due to an interaction between rs2569190 in CD14 and gender.

RATIONALE: Since identifying gender-specific genetic associations may have a significant impact on public health, we studied the interaction between rs2569190 in CD14 (cluster of differentiation 14) and gender in relation to the lipid traits in two independent populations. METHODS: We first tested the interaction in a discovery population (SFS, n = 956), then replicated it in an independent population (LGP, n = 460), followed by a meta-analysis (n = 1,416). Finally, stratification according to gender was conducted to test the association between rs2569190 and lipid traits. Binary multiple logistic regression models were used while correcting for many confounders. Power calculations were also performed. RESULTS: An interaction between rs2569190 and gender, which increased the risk of total cholesterol levels in SFS, was found (OR = 2.151 and P = 0.05). This interaction was further replicated in the LGP (OR = 1.353 and P < 0.001), and the meta-analysis showed an overall significant interaction (OR = 1.436 and Pmeta = 0.02). Similarly, the meta-analysis showed an overall significant positive effect (OR = 1.204 and Pmeta = 0.004) for low-density lipoprotein cholesterol levels. Overall, 1,416 patients were evaluated, and the statistical heterogeneity was low, with I2 estimates ranging between 0% and 22.2%. In contrast, rs2569190 in CD14 did not show any significant interaction with gender influencing high-density lipoprotein levels and triglycerides levels in both populations. CONCLUSION: An interaction between rs2569190 in CD14 and gender increased the risk of hypercholesterolemia in two independent populations with a gender-specific effect in males.

Surveillance Study of Acute Gastroenteritis Etiologies in Hospitalized Children in South Lebanon (SAGE study).

PURPOSE: Acute gastroenteritis (AGE) is a major cause of morbidity and remains a major cause of hospitalization. Following the Syrian refugee crisis and insufficient clean water in the region, this study reviews the etiological and epidemiological data in Lebanon. METHODS: We prospectively analyzed demographic, clinical and routine laboratory data of 198 children from the age of 1 month to 10 years old who were admitted with the diagnosis of AGE to a private tertiary care hospital located in the district of Nabatieh in south Lebanon. RESULTS: Males had a higher incidence of AGE (57.1%). Pathogens were detected in 57.6% (n=114) of admitted patients, among them single pathogens were found in 51.0% (n=101) of cases that consisted of: Entamoeba histolytica 26.3% (n=52), rotavirus 18.7% (n=37), adenovirus 6.1% (n=12) and mixed co-pathogens found in 6.6% (n=13). Breast-fed children were significantly less prone to rotavirus (p=0.041). Moreover, children who had received the rotavirus vaccine were significantly less prone to rotavirus (p=0.032). CONCLUSION: Our findings highlight the high prevalence of E. histolytica infection as the major cause of pediatric gastroenteritis in hospitalized children, during the summer period likely reflecting the insanitary water supplies and lack of hygiene. Moreover the 42.4% of unidentified causative pathogens should prompt us to widen our diagnostic laboratory arsenal by adopting new diagnostic technologies.

Dataset on significant role of Candesartan on cognitive functions in rats having memory impairment induced by electromagnetic waves.

Rapid growing of mobile phones users has raised about the possible effects of these electromagnetic waves (EMW) on human health. Many studies have examined the role of these EMW on biological systems, but the results are still contradictory and controversial. In addition to EMW, over-activation of angiotensin type 1 receptor (AT1R) has been associated with cognitive decline, incidence and progression of neurodegenerative diseases. Candesartan, an AT1R blocker, is well recognized for treatment of hypertension. However, its role on cognitive functions such as spatial and recognition memory remains elusive. Thus, young rats were divided into 3 groups: control, exposed to radiofrequency electromagnetic waves (EMW), and exposed to EMW during Candesartan treatment (EMW+Cand). Spatial memory performance was assessed using the object recognition test and recognition memory performance using Morris water maze test. Significant differences where found between EMW exposed rats and EMW+Cand exposed rats treated with Candesartan compared to control, EMW group impaired learning, spatial and short term memory along with unaffected sensorimotor function whereas EMW+Cand group improved learning, spatial memory and short term memory deficit induced by EMW in addition to absence of its role on sensorimotor function. Although our data provides evidences of the protective role of Candesartan against EMW-induced cognitive decline, more future studies are still needed to confirm these findings which can provide new fields in treatment of EMW-induced damage by Candesartan.

Resistin-like molecule-beta inhibits SGLT-1 activity and enhances GLUT2-dependent jejunal glucose transport.

OBJECTIVE: An increased expression of RELM-beta (resistin-like molecule-beta), a gut-derived hormone, is observed in animal models of insulin resistance/obesity and intestinal inflammation. Intestinal sugar absorption is modulated by dietary environment and hormones/cytokines. The aim of this study was to investigate the effect of RELM-beta on intestinal glucose absorption. RESEARCH DESIGN AND METHODS: Oral glucose tolerance test was performed in mice and rats in the presence and the absence of RELM-beta. The RELM-beta action on glucose transport in rat jejunal sacs, everted rings, and mucosal strips was explored as well as downstream kinases modulating SGLT-1 and GLUT2 glucose transporters. RESULTS: Oral glucose tolerance test carried out in rodents showed that oral administration of RELM-beta increased glycemia. Studies in rat jejunal tissue indicated that mucosal RELM-beta promoted absorption of glucose from the gut lumen. RELM-beta had no effect on paracellular mannitol transport, suggesting a transporter-mediated transcellular mechanism. In studies with jejunal mucosa mounted in Ussing chamber, luminal RELM-beta inhibited SGLT-1 activity in line with a diminished SGLT-1 abundance in brush border membranes (BBMs). Further, the potentiating effect of RELM-beta on jejunal glucose uptake was associated with an increased abundance of GLUT2 at BBMs. The effects of RELM-beta were associated with an increased amount of protein kinase C betaII in BBMs and an increased phosphorylation of AMP-activated protein kinase (AMPK). CONCLUSIONS: The regulation of SGLT-1 and GLUT2 by RELM-beta expands the role of gut hormones in short-term AMPK/protein kinase C mediated control of energy balance.