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.

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.

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.

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.