Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study).

BACKGROUND: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.

Assessment of fibroblast growth factor 21 in children with type 1 diabetes mellitus in relation to microvascular complications.

INTRODUCTION: Type 1 diabetes mellitus (DM1) represents a growing global health problem with significant morbidity. Fibroblast growth factor 21 (FGF21) is an adipokine expressed predominantly in the liver that plays an important role in metabolic regulation. AIM OF THE STUDY: This study assesses FGF21 levels in children with DM1, in comparison to controls, and correlates them with diabetes duration, glycated haemoglobin (HbA1c), and diabetic microvascular complications. MATERIAL AND METHODS: Fifty children with DM1, aged between 5 and 16 years, were studied regarding their diabetes duration, HbA1c, urinary albumin creatinine ratio (UACR), fundus, and FGF21 level. They were compared to 50 healthy controls. RESULTS: The median FGF21 of the studied children with DM1 was 150 pg/ml, range 50-350 pg/ml; while that of the controls was 35 pg/ml, range 20-50 pg/ml. FGF21 level was significantly higher in children with DM1 than in controls ( p < 0.001). Moreover, it was significantly and positively correlated with diabetes duration, mean blood glucose level, and HbA1c ( p < 0.001, p = 0.015, p = 0.018, respectively). Interestingly, the FGF21 level was not significantly elevated in children with DM1 having diabetic nephropathy and retinopathy ( p = 0.122, p = 0.298, respectively). CONCLUSIONS: FGF21 is significantly higher among children with DM1 than in controls. However, its role in diabetic microvascular complica-tions needs further assessment.

Changes in early optical coherence tomography angiography among children and adolescents with type 1 diabetes: Relation to fibroblast growth factor 21.

AIMS: Current diagnostic and treatment modalities target late stages of diabetic retinopathy (DR) when retinopathy has already been established. Novel and more sensitive strategies are needed. Optical coherence tomography angiography (OCTA) permits non-invasive visualisation of retinal microcirculation. Fibroblast growth factor-21 (FGF21) plays an important role in glucose and lipid homoeostasis. This study assesses early OCTA changes among children and adolescents with type 1 diabetes (T1DM) compared to fundus photography and correlates them to diabetes-duration, glycaemic control, and FGF21; hence, it determines their value in early detection of DR. METHODOLOGY: Hundred children and adolescents with T1DM were assessed for diabetes-duration, insulin therapy, hypoglycemia, and diabetic-ketoacidosis frequency, Tanner staging, glycated-haemoglobin (HbA1c), fasting lipids, urinary albumin/creatinine ratio, and serum FGF21. OCTA and fundus photography were done for the studied patients and 100 age, gender, and Tanner matched healthy controls. RESULTS: The mean age of the children and adolescents with T1DM was 10.84 years, their mean diabetes-duration was 3.27 years and their median FGF21 was 150 pg/ml. FGF21 was significantly higher among children and adolescents with T1DM than controls (p < 0.001). Children and adolescents with T1DM had a significantly larger foveal avascular zone (FAZ) and lower peripapillary and inside-disc capillary densities (p < 0.05); with no significant fundus photography difference (p = 0.155) than controls. FAZ was positively correlated and peripapillary and inside-disc capillary densities were negatively correlated with diabetes-duration, HbA1c, FGF21, and Tanner stage. FGF21 was significantly higher in T1DM children and adolescents having OCTA changes compared to those with normal OCTA (p = 0.002). Multivariate-regression revealed that FAZ is independently associated with diabetes-duration, HbA1c and FGF21. CONCLUSIONS: OCTA changes start early in children and adolescents with T1DM long before the fundus changes. These changes are correlated with diabetes-duration, puberty, glycaemic, and FGF21.

The Association between Treatment Modality, Lipid Profile, Metabolic Control in Children with Type 1 Diabetes and Celiac Disease-Data from the International Sweet Registry.

BACKGROUND AND AIMS: A higher frequency of dyslipidemia is reported in children with type 1 diabetes (T1D) and celiac disease (CD). Recently, continuous subcutaneous insulin infusion (CSII) has been associated with better lipid profiles in patients with T1D. The aim of this study was to investigate the association between treatment modality and lipid profile, metabolic control, and body mass index (BMI)-SDS in children with both T1D and CD. METHODS: Cross-sectional study in children registered in the international SWEET database in November 2020. Inclusion criteria were children (2-18 years) with T1D and CD with available data on treatment modality (CSII and injections therapy, IT), triglyceride, total cholesterol, HDL, LDL, dyslipidemia, HbA1c, and BMI-SDS. Overweight/obesity was defined as > +1 BMI-SDS for age. Data were analyzed by linear and logistical regression models with adjustment for age, gender, and diabetes duration. RESULTS: In total 1009 children with T1D and CD (female 54%, CSII 54%, age 13.9 years ±3.6, diabetes duration 7.2 years ±4.1, HbA1c 7.9% ±1.4) were included. Significant differences between children treated with CSII vs. IT were respectively found; HDL 60.0 mg/dL vs. 57.8 mg/dL, LDL 89.4 mg/dL vs. 94.2 mg/dL, HbA1c 7.7 vs. 8.1%, BMI-SDS 0.4 vs. 0.6, overweight and obesity 17% vs. 26% (all p < 0.05). CONCLUSIONS: CSII is associated with higher HDL and lower LDL, HbA1c, BMI-SDS, and percentage of overweight and obesity compared with IT in this study. Further prospective studies are required to determine whether CSII improves lipid profile, metabolic control and normalize body weight in children with both T1D and CD.

Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats.

BACKGROUND: Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. RESULTS: Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. CONCLUSION: These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

Clinical characteristics and outcome of hospitalized children and adolescent patients with type 1 diabetes during the COVID-19 pandemic: data from a single center surveillance study in Egypt.

OBJECTIVES: COVID-19 pandemic significantly impacted the diagnosis of type 1 diabetes and its acute complications. Thus, the study aimed to evaluate the characteristics of pediatric patients with type 1 diabetes hospitalized during the first wave of the pandemic and the prevalence of new onset diabetes among patients with evidence of COVID-19 infection. METHODS: A single-center surveillance study included all patients with diabetes admitted to Children's Hospital, Ain Shams University, in Egypt between May to August 2020. Data were collected to evaluate patients' clinical and laboratory characteristics as well as their outcomes. RESULTS: Thirty-six patients were admitted during the study period. The mean age was 8.4 ± 3.8 years. Patients presented late to the emergency department with a mean delay of 3.05 ± 1.19 days from onset of symptoms. 34/36 patients presented in diabetic ketoacidosis (DKA), 50% presenting in severe DKA. Almost 81% of the patients were newly diagnosed. During the study period, SARS-CoV-2 PCR was found positive in four patients, COVID Ig M antibodies were positive in another two patients; all were symptomatic requiring ICU admission. Four patients showed a picture suggestive of the multi-inflammatory syndrome (MIS-C); cardiac affection was a constant feature. CONCLUSIONS: The pandemic affected both the prevalence and severity of DKA among pediatric patients. The increased prevalence of severe DKA could be partly related to delayed hospital admission or the effect of COVID-19 in triggering DKA. Efforts should be done to continuously raise awareness about diabetes in children as well as the importance of seeking timely medical guidance.

Soluble urokinase plasminogen activator receptor in type 1 diabetic children, relation to vascular complications.

BACKGROUND: Endothelial dysfunction caused by chronic inflammation is the cornerstone of vascular complications in type 1 Diabetes-Mellitus (T1DM). Soluble Urokinase Plasminogen Activator Receptor (SuPAR) is a novel marker of inflammation and endothelial dysfunction. AIM: To evaluate SuPAR in T1DM children and correlate it to diabetic vascular complications. METHODS: Seventy T1DM children and 40 matched healthy controls were studied focusing on disease duration, insulin therapy and symptoms of diabetic complications. Blood-pressure, fundus and screening for peripheral-neuropathy were done. Fasting lipid profile, fraction-C of glycosylated hemoglobin (HbA1c%), Urinary albumin excretion (UAE), estimated-glomerular filtration rate (eGFR) and SuPAR were measured. Internal aortic diameter was measured with calculation of aortic distensibility and stiffness index. RESULTS: Sixteen T1DM patients(22.9%) had peripheral neuropathy, 12(17%) had nephropathy and none had retinopathy. SuPAR was significantly elevated in diabetic nephropathy (p < 0.01) and neuropathy (p < 0.01). Aortic stiffness index was significantly higher (p < 0.01) whereas, aortic strain and distensibility were significantly lower (p < 0.01) in T1DM than controls. SuPAR was significantly correlated to disease duration (p < 0.01), systolic blood pressure (p < 0.01), total cholesterol (p < 0.01), triglycerides (p < 0.01), UAER (p < 0.01) and aortic strain (0.013). CONCLUSION: Increased SuPAR early in diabetes might become a useful indicator of developing vascular complications. Further prospective studies are needed to determine the cut-off level of SuPAR for detection of T1DM and its complications.

Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in Egyptian patients with Beta Thalassemia Major.

OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (ß-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS: Hundred patients with ß-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with ß-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with ß-TM.

Plasma thrombin-activatable fibrinolysis inhibitor levels in children and adolescents with type 1 diabetes mellitus: possible relation to diabetic microvascular complications.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of fibrinolysis isolated from human plasma. This study was designed to investigate the association between TAFI levels in relation to metabolic control, microvascular complications and lipid profile in a cohort of Egyptian children and adolescents with type 1 diabetes mellitus (T1DM). Eighty normotensive nonobese type 1 diabetic patients (45 with and 35 without microvascular complications) with a mean age of 12.75 ± 3.6 years and mean disease duration of 7.42 ± 2.4 years in addition to 60 sex and age-matched normal individuals were enrolled in this study. Anthropometric measurements, blood pressure and microvascular complications were analysed. HbA1c, albumin-to-creatinine ratio in urine, lipid profile and TAFI levels were measured. Plasma level of TAFI in diabetic patients was significantly elevated, compared with normal individuals (16 ± 2.8 vs. 10.3 ± 0.7 µg/ml; P < 0.004). Plasma level of TAFI in diabetic patients with microvascular complications was significantly higher than in diabetic patients without complications (17.9 ± 1.8 vs. 12.9 ± 0.6 µg/ml; P < 0.001). Plasma TAFI levels were positively correlated with HbA1c levels (r = 0.38; P < 0.03) and SBP (r = 0.37; P < 0.02). Total cholesterol and triglycerides were higher in patients with microvascular complications than in those without complications (P < 0.001, P < 0.05, respectively). Our results showed that TAFI is considered a valid predictor for microvascular complications with best cut off value 15 µg/ml with sensitivity of 99% and specificity of 100%. Our data imply that increased plasma TAFI as well as high lipid levels may be involved in the mechanism of vascular endothelial damage in patients with T1DM. This suggests the possibility of TAFI participating in the mechanism of hypofibrinolysis, hence occurrence of microvascular complications in diabetes.

Evoked potentials and neurocognitive functions in pediatric Egyptian Gaucher patients on enzyme replacement therapy: a single center experience.

BACKGROUND: Effectiveness of enzyme replacement therapy (ERT) in reverting hematologic, skeletal, and visceral symptoms in Gaucher disease (GD) has been demonstrated, although, its efficacy in neurologic involvement is still debated. AIM: We evaluated the extent of neuro-cognitive dysfunction using brain stem evoked potential in GD3 patients, age-matched controls, and GD1 patients without neurological manifestations served as disease control group. METHODS: Study included 56 GD (36 had type 1, 20 had type 3) under ERT. Investigations included complete blood count, beta glucosidase assay in peripheral leucocytes, plasma chitotriosidase and bone marrow examination, electroencephalography, brain stem auditory (AEP), somatosensory (SSEP) and visual evoked potentials (VEP) as well as IQ testing. RESULTS: Both types of GD showed significantly higher mean latency at 75 on left eye, lower PP amplitude ratio, higher latency at 75, 100, 145, lower amplitude, and higher Lat Diff LT-RT ms and Lt-Rt % compared to controls (p < 0.05) with no difference between both groups in other values of VEP. Both groups showed significantly prolonged latency of N 13-19 compared to controls (p < 0.05) with positive correlation between age and duration of therapy with parameters of SSEP (p < 0.01). Both groups of GD had significantly prolonged latency of the mean waves of AEP compared to controls (p < 0.05) with no significant difference between both groups. There was a negative correlation between age and waves II, III, I-III, I-V and threshold values of AEP. IQ level was positively correlated with AEP values. Severity scoring tool was positively correlated with AEP and SSEP values. CONCLUSIONS: Electrophysiological abnormalities were present in both types of GD and have been correlated to cognitive function and disease characteristics.

An Egyptian case of congenital hyperinsulinism of infancy due to a novel mutation in KCNJ11 encoding Kir6.2 and response to octreotide.

Congenital hyperinsulinism of infancy (CHI) is a rare heterogeneous disease mostly attributable to mutations in the genes encoding the KATP channel subunits found in pancreatic ß-cells. Here, we report a child presenting at day 1 with persistent hyperinsulinemic hypoglycemia and who underwent open laparotomy and subtotal pancreatectomy with resection of tail and body of pancreas at 30 days of age. Normoglycemia was restored by Octreotide that was discontinued when the child was 7-month old. However, 3 months later Octreotide was re-administered as hypoglycemic attacks recurred. On follow-up, the child has adequate glycemic control and is thriving well with no neurodevelopmental morbidity. Genetic analysis revealed the novel mutation c.407G > A [p.R136H] in KCNJ11 encoding Kir6.2, confirming the diffuse form of CHI. This is to our knowledge the first reported Egyptian case of CHI due to a mutation in KCNJ11.

D-dimer assay in Egyptian patients with Gaucher disease: correlation with bone and lung involvement.

Gaucher disease is the most frequent lysosomal storage disorder. Bone and lung involvement are two major causes of morbidity in this disease. D-dimer is a reliable indicator of active microvascular thrombosis, even in patients without overt hypercoagulation. This study aimed to assess D-dimer levels in Gaucher disease, correlating this marker to clinical characteristics and radiological parameters to investigate its role as a potential predictor for the occurrence and severity of skeletal and pulmonary manifestations. The study population consisted of 56 Egyptian patients with Gaucher disease, 36 had type 1 Gaucher disease (64.3%) and 20 had type 3 Gaucher disease (35.7%). Thirty healthy individuals were enrolled as a control group. D-dimer levels were significantly higher in all patients with Gaucher disease compared with controls (P < 0.001). Patients with type 3 showed significantly higher D-dimer concentrations compared with type 1 (P < 0.001). Pulmonary involvement was present in a significant proportion among type 3 Gaucher patients (P < 0.05), whereas bone changes were present in a higher percentage in type 1 compared with type 3 Gaucher patients. D-dimers were significantly higher in patients with abnormal MRI findings of the long bones and in those with ground glass appearance on high-resolution computerized tomography of the chest compared with patients with normal radiology (P < 0.001). Splenectomized patients displayed significantly higher D-dimer levels compared with nonsplenectomized patients (P < 0.001). Our results suggest that D-dimer is significantly elevated in Gaucher disease, particularly type 3, and may be considered as a potential marker of risk prediction of bone and lung involvement that could be used to monitor treatment response.