Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is a significant health challenge, especially for children, owing to its chronic autoimmune nature. Although the exact etiology of T1DM remains elusive, the interplay of genetic predisposition, immune responses, and environmental factors are postulated. Genetic factors control immune reactivity against ß-cells. Given the pivotal roles of CIITA and CLEC2D genes in modulating a variety of immune pathologies, we hypothesized that genetic variations in CIITA and CLEC2D genes may impact T1DM disease predisposition. This study was designed to explore the association between gene polymorphisms in CIITA (rs8048002) and CLEC2D (rs2114870) and type 1 diabetes (T1DM), with a focus on analyzing the functional consequence of those gene variants. Methods: The study enlisted 178 healthy controls and 148 individuals with type 1 diabetes (T1DM) from Suez Canal University Hospital. Genotyping for CIITA and CLEC2D was done using allelic-discrimination polymerase chain reaction (PCR). Levels of glycated hemoglobin (HbA1c) and lipid profiles were determined through automated analyzer, while fasting blood glucose and insulin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RegulomeDB was used to examine the regulatory functions of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants. Results: Analysis of the genotype distribution of the CIITA rs8048002 polymorphism revealed a significantly higher prevalence of the rare C allele in T1DM patients compared to the control group (OR = 1.77; P = 0.001). Both the CIITA rs8048002 heterozygote TC genotype (OR = 1.93; P = 0.005) and the rare homozygote CC genotype (OR = 3.62; P = 0.006) were significantly more frequent in children with T1DM when compared to the control group. Conversely, the rare A allele of CLEC2D rs2114870 was found to be significantly less frequent in T1DM children relative to the control group (OR = 0.58; P = 0.002). The heterozygote GA genotype (OR = 0.61; P = 0.033) and the rare homozygote AA genotype (OR = 0.25; P = 0.004) were also significantly less frequent in T1DM patients compared to the control group. Both CIITA (rs8048002) and CLEC2D (rs2114870) gene variants were predicted to have regulatory functions, indicated by a RegulomeDB score of (1f) for each. Conclusion: The rare C allele of CIITA rs8048002 genetic variant was associated with an increased risk of developing T1DM, while the less common A allele of CLEC2D rs2114870 was associated with a reduced risk of T1DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01402-w.

Is subclinical atherosclerosis associated with visceral fat and fatty liver in adolescents with type 1 diabetes?

INTRODUCTION: There is a 3-fold higher prevalence of cardiovascular complications in patients with type 1 diabetes. The aim was to assess the relationship between subclinical atherosclerosis and visceral fat and fatty liver in diabetic adolescents. MATERIAL AND METHODS: The study was performed on 110 adolescents with type 1 diabetes (T1D) attending the Pediatric Diabetes Clinic of the University Hospital, Ismailia, Egypt. Their mean age was 14.2 ±0.7 years with a mean duration of diabetes 6 ±0.3 years. They were divided into group 1 which consisted of 55 adolescents with T1D and normal carotid intima media thickness (cIMT) and the second group which included 55 adolescents with T1D and subclinical atherosclerosis. All adolescents were normotensive, normo-albuminuric and had no retinopathy. Visceral fat thickness was measured as the distance between the anterior wall of the aorta and the posterior surface of the rectus abdominis muscle. Hepatic steatosis was diagnosed based on enlarged liver size and evidence of diffuse hyper-echogenicity of liver relative to kidneys. RESULTS: The mean visceral fat was significantly higher in adolescents with increased cIMT (4.8 ±1.6) than in the normal thickness group (3.9 ±1.4). Liver size was also significantly larger in the former group (13.73 ±2.26 versus 12.63 ±2.20) (p = 0.022). After adjusting for other variables, logistic regression demonstrated that glycated hemoglobin (HbA1c) and fatty liver are independent factors affecting cIMT, OR = 1.426 (p < 0.05) and OR = 4.71 (p < 0.05). CONCLUSIONS: In the present study, fatty liver and HbA1c were associated with subclinical atherosclerosis in lean adolescents with T1D.

Pattern and outcome of pediatric head injuries in the Suez Canal Region: A follow-up study.

BACKGROUND: A significant number of children sustain head injuries every year. Despite this, few studies in Egypt have provided detailed information about these injuries. AIM: The aim of this study was to investigate the epidemiology and outcome of head injury among children presenting to the emergency department in the Suez Canal University Hospital. MATERIALS AND METHODS: A clinical follow-up study including 70 patients, aged 18 years or less, who presented to the emergency department, with head injuries, in the period from March 2014 to February 2015. Patients were grouped according to their ages into three subgroups: <2, 2-5, and >5 years old. Collected data included patients' demographics, injury causes, severity, timing of injuries, and the eventual outcome after a follow-up period of 3 months. Severity of head injury was based on the general level of consciousness using the Pediatric Glasgow Coma Scale. The functional outcome at the final follow-up was assessed using the King's Outcome Scale for Childhood Head Injury. RESULTS: Male-to-female ratio was 1.4 : 1. The highest incidence was in the age group of 2-5 years. The main causes were traffic injury and falls (35.7% for each), followed by home injuries (21%) and sport-related injuries (7%). Regarding the severity of injury, 81% of children had mild injury, 13% had moderate injury, and 6% had severe injury. Concussion was the most common type of head injury (56%), followed by skull fractures (23%). The functional outcome was assessed at the time of discharge, and 3 months later. Good recovery was achieved in 91% of children; moderate disability was present in 7% of children; and less than 2% of the children showed sustained severe disability. CONCLUSION: Children aged 5 years or less comprised 75% of the children who presented to the hospital following head injury. Falls and road traffic accidents were the most common causes of injury. Most injuries were of mild severity, and concussion was the most common encountered type of injury. Assessment of functional outcome showed good recovery in most children. Enforcement of strict effective regulations and observing safety measures during driving by authorities is needed to reduce traffic accidents. Health education programs for parents about careful supervision and first aid should be provided to help prevent child head injury and its disastrous consequences.

Anti-cyclic citrullinated peptide (anti-CCP) antibody in juvenile idiopathic arthritis (JIA): correlations with disease activity and severity of joint damage (a multicenter trial).

OBJECTIVES: To determine the presence of anti-CCP antibodies in children with JIA and to correlate its levels with Juvenile Arthritis Disease Activity Score (JADAS) and Sharp/Van der Heijde Score. METHODS: The study population comprised 54 cases, with 29 patients (53.7%) who had polyarticular onset, 19 (35.2%) had pauciarticular onset and six (11.1%) had systemic onset JIA. All patients were subjected to complete clinical examination, assessment of disease activity by JADAS-27 (ESR), and radiological damage by Sharp/Van der Heijde Score. Laboratory investigations included a complete blood count, ESR first hour, ANA, IgM Rheumatoid factor (RF) and serum anti-CCP2, and were used for further correlations. RESULTS: RF was positive in 14 (25.9%) patients and anti-CCP antibodies were positive in 13 (24.1%) patients, 12 of whom had polyarticular onset. There were significant differences between groups relative to RF (F=8.577, P=0.001) and anti-CCP antibodies (F=4.845, P=0.012) being higher in JIA patients with polyarticular onset compared to other subsets of JIA patients. The mean total of the Sharp/Van der Heijde Score was significantly higher among polyarticular-JIA patients with positive anti-CCP antibodies compared to those negative for anti-CCP antibodies (P=0.05). Anti-CCP positively correlated with CRP (r=0.521, P<0.001) and Sharp/Van der Heijde Score (r=0.457, P<0.001). CONCLUSION: Anti-CCP antibodies were prevalent among JIA patients with polyarticular patterns compared to other disease patterns. Anti-CCP positively and significantly correlated with Sharp's score and CRP levels. Given that anti-CCP may be influential in the choice of the best therapeutic strategy in JIA with polyarticular pattern of onset.

Echocardiographic evaluation of cardiac structure and function in obese Egyptian adolescents.

OBJECTIVE: The objective of this study was to detect structural and functional changes in the left and right ventricles in obese Egyptian adolescents. Methods and results Anthropometric and echocardiographic parameters, including tissue Doppler imaging, were obtained from 70 obese adolescents with average body mass index of 34 plus or minus 3.8 and compared with 50 age- and sex-matched controls, with a body mass index of 21.6 plus or minus 1.9. Cardiac dimensions, stroke volume, left ventricular and right ventricular systolic and diastolic functions were evaluated. The obese group had a higher end-diastolic septal and posterior wall thickness and left ventricular mass index than the non-obese group. Body mass index, mid-arm and hip circumference values showed significant correlations with these echocardiographic variables. Systolic and diastolic functions of the left ventricle were normal in both groups, although stroke volume was high in the obese group. The right ventricle tissue Doppler parameters were similar in both groups. However, the S wave of the septal/lateral tricuspid valve annulus was reduced in the obese group, but not to the level reflecting systolic dysfunction. This was inversely correlated with hip, waist, and mid-arm circumference. Stepwise multiple regression analysis showed that the mid-arm and hip circumference followed by the body mass index are significant predictors of these early cardiac abnormalities. CONCLUSION: Left ventricular hypertrophy is present in obese children, although both systolic and diastolic functions are normal. Tissue Doppler imaging revealed a minor, but still significant, reduction in the right ventricular systolic function. Mid-arm and hip circumference are predictors of left ventricular hypertrophy.

Subclinical atherosclerosis in obese adolescents with normal left ventricular function.

OBJECTIVE: To assess the impact of obesity on carotid intima media thickness and left ventricular (LV) mass in obese adolescents. METHODS: The study included 52 obese adolescents (mean age 14.16+/-2.64 years) and 52 healthy adolescents who served as a control group (mean age 12+/-2.3 years), who were attended the outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. The study population was submitted for medical history, clinical examination, laboratory investigations (fasting blood sugar and lipid profile), and echocardiographic examination of LV mass and dimensions. Assessment of carotid intima-media thickness was carried out by using carotid duplex. All children had normal LV function. RESULTS: Obese adolescents had a significant increase in total cholesterol, triglyceride, LDL-C, and low HDL-C compared to the control group. Also, there was a significant increase in blood pressure, carotid intima media thickness, LV mass, and LV mass index. There was a significant correlation between BMI and dyslipidemia, blood pressure, carotid intima/media thickness, LV mass, and posterior wall thickness. Carotid intima-media thickness had a significant correlation with increased LDL-C and low HDL-C, blood pressure, LV mass, and posterior wall thickness. CONCLUSION: Obesity in childhood and adolescents is associated with subclinical atherosclerosis. Although obese children had no LV dysfunction, yet there are LV structure changes.