Search

Congenital hyperinsulinism is the commonest cause of hypoglycemia in childhood. Focal form of congenital hyperinsulinism is present in half of affected patients requiring surgical management. We present the case of two sisters diagnosed with focal form of congenital hyperinsulinism and the impact of diagnostic process on clinical management and postoperative complications. In Older sister subtotal pancreatectomy was performed causing insulin-dependent diabetes and need for pancreatic enzymes substitution. In second case of younger sister the decision about the surgery was made after 18-F-DOPA PET scan and selective resection of identified focal lesion was applied. In effect there were no complications after surgery and complete recovery was observed. 18-F- -DOPA PET imaging allows to differentiate between diffuse and focal form of congenital hyperinsulinism and determines further management. Identification and adequate localization of focal changes allow surgical planning and in effect to perform selective focal surgery that significantly decreases postoperative complications. [ABSTRACT FROM AUTHOR]

Purpose. The study aimed to investigate the influence of estrogen receptor α (ER-α) genotypes on inflammatory response and development of microvascular complications in girls with type 1 diabetes. Methods. 152 young regularly menstruating girls with diagnosed type 1 diabetes and 84 young, healthy menstruating girls were recruited. ER-α genotypingwas carried out by PCR. Serum concentrations of 17β-estradiol, as well as IL-6, TNF-α, VEGF, and IL-10, weremeasured.CD4+Foxp3+ TH17 cells were isolated and analyzed by flow cytometry. Results. Type 1 diabetic girls carrying TT genotype were characterized by the lowest serum estradiol level and IL-10 and highest IL-6, TNF-α , and VEGF.The association between the level of certain cytokine and the genetic variant of estrogen receptor α polymorphism was analyzed. Frequencies of CD4+Foxp3+ TH17 cells were also enhanced in TT bearing girls with type 1 diabetes and correlated with the level of analyzed cytokines. In addition, the correlation between serum estradiol level and cytokine concentrations was observed. Conclusions. We propose that TT variant of estrogen receptor α polymorphism may be associated with enhanced inflammatory response, which in turn may lead to acceleration of diabetic retino- and nephropathy in girls with type 1 diabetes. This finding may help the physicians to predict the onset and progression of diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4-18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (P = 0.0003), poor metabolic control (P = 0.0001), and carriage of the A allele of the FTO rs9939609 gene (P = 0.02). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with ClinicalTrials.gov (NCT01279161). [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is the most common monogenic disease. FH is caused by autosomal dominant mutations in the gene encoding the LDL receptor, apolipoprotein B (ApoB) or PCSK9. Aim of the study was to analyze the clinical data of children and adolescents with heterozygous familial hypercholesterolemia confirmed in molecular tests from the Department of Paediatrics, Diabetology and Endocrinology and preliminary assessment of the effects of treatment. Materials and methods. The study included children with elevated cholesterol levels. All patients were excluded secondary causes of hypercholesterolemia. In 127 patients molecular tests for mutation in the LDL receptor and Apo B gene were performed. Results. Currently under the care of the Department of Paediatrics, Diabetology and Endocrinology are 43 patients with genetically confirmed FH and more than 27 patients with suspicion of familial hypercholesterolemia during molecular studies. All patients with FH family history of the cardiovascular system diseases was positive. Patients with FH initially the average total cholesterol level was 281,6±61,6 mg/dl, LDL cholesterol 205,24±70,51 mg/dl. In genetic studies in 74% of patients mutations in the LDL receptor gene and in 26% of patients mutations in the Apo B gene was found. Treatment with statins in 27 patients and with ezetimibe in 2 patients with FH was started. The average level of total cholesterol in the control tests after 6-8 weeks of treatment was 203,7±38,1 mg/dl, LDL cholesterol 128,9±43,4 mg/dl. In the group of patients treated with pharmacological therapy, no adverse side effects of the treatment were reported. It was noticed that with children being treated pharmacological the value of IMT was lower comparing to the children solely on a diet. Conclusions. Lipid disorders should be diagnosed and treated from the earliest years of life, especially in children with a positive family history of the cardiovascular system diseases. Currently, the most effective treatment in children seems to be a therapy with statins. Longer follow up and monitoring of the effectiveness and safety of the treatment is needed. [ABSTRACT FROM AUTHOR]

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Experimental near edge X-ray absorption fine structure (NEXAFS) spectra, X-ray photoelectron (XP) spectra and Auger electron spectra are reported for sulfur in ionic liquids (ILs) with a range of chemical structures. These values provide experimental measures of the atomic charge in each IL and enable the evaluation of the suitability of NEXAFS spectroscopy and XPS for probing the relative atomic charge of sulfur. In addition, we use Auger electron spectroscopy to show that when XPS binding energies differ by less than 0.5 eV, conclusions on atomic charge should be treated with caution. Our experimental data provides a benchmark for calculations of the atomic charge of sulfur obtained using different methods. Atomic charges were computed for lone ions and ion pairs, both in the gas phase (GP) and in a solvation model (SMD), with a wide range of ion pair conformers considered. Three methods were used to compute the atomic charges: charges from the electrostatic potential using a grid based method (ChelpG), natural bond orbital (NBO) population analysis and Bader's atoms in molecules (AIM) approach. By comparing the experimental and calculated measures of the atomic charge of sulfur, we provide an order for the sulfur atoms, ranging from the most negative to the most positive atomic charge. Furthermore, we show that both ChelpG and NBO are reasonable methods for calculating the atomic charge of sulfur in ILs, based on the agreement with both the XPS and NEXAFS spectroscopy results. However, the atomic charges of sulfur derived from ChelpG are found to display significant, non-physical conformational dependence. Only small differences in individual atomic charge of sulfur were observed between lone ion (GP) and ion pair IL(SMD) model systems, indicating that ion-ion interactions do not strongly influence individual atomic charges.

Introduction: Two forms of diabetes can be distinguished during pregnancy: gestational diabetes and pregestational diabetes, which exists prior to pregnancy. In young women, the most common form of pregestational diabetes is type 1 diabetes (T1D). Regarding the decreasing age of sexual initiation and health risks for the mother and child related to hyperglycemia, it is essential that adolescents with T1D possess proper knowledge of pregnancy planning and diabetes management in case of pregnancy. Preconception counseling in adolescent patients with T1D remains a challenge for the whole therapeutic team., Aim of the Study: Assessing the awareness of consequences of uncontrolled diabetes on the course of pregnancy and fetal development among patients with T1D., Material and Methods: The study was carried out in the group of 70 patients with T1D, aaged 15-18 years. The survey was consisted of 25 questions regarding health status, lifestyle, the knowledge of self-management of diabetes and the impact of diabetes on pregnancy and fetal development. Respondents were asked to indicate the sources of information from which they had gianed knowledge about the aforesaid issues. The data obtained were statistically analyzed., Results: 20% (n=14) of respondents declared sexual activity. In the group of sexually active patients, in 50% (n=7) last HbA1c level, reported by subjects, was between 7.5-9%, and in 21.4% (n=3) >9%. The patients were aware of the consequences of uncontrolled diabetes on fetal development, however their knowledge was unsatisfactory. Surveyed adolescents indicated metabolic disorders (61.4 %, n=43), central nervous system malformations (55.7%, n=39) and heart defects (47.1%, n=33) as the most frequent complications. The respondents gathered knowledge mainly from a diabetologist (40%, n=28) and the Internet (40%, n=28). The majority of patients stated that preconception care should be provided by a diabetologist (88.6%, n=62) or a gynecologist (70%, n=49)., Conclusion: In spite of continuous diabetes care, adolescents with T1D do not possess sufficient knowledge regarding the consequences of hyperglycemia during pregnancy. This study has emphasized the need for including reproductive health issues in diabetes education addressed to adolescent patients., (© Polish Society for Pediatric Endocrinology and Diabetology.)

IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4 + CD25 high FOXP3 + T cells. CD4 + CD25 high FOXP3 + as well as CD4 + CD25 high FOXP3 + ST2 + Tregs were analyzed by flow cytometry. In a group of patients with type 1 diabetes in vitro IL-33 treatment induced regulatory CD4 + CD25 high FOXP3 + cell frequencies as well as upregulating the surface expression of ST2 molecule. In addition, the number of CD4 + CD25 high FOXP3 + cells carrying ST2 receptor increased significantly. Similar effect was observed in case of the FOXP3 expression. We did not observe any significant changes in IL-33 treated cells of healthy controls. The level of ST2 was higher in serum of patients with type 1 diabetes in comparison to their healthy counterparts. We propose that IL-33 becomes an additional immunostimulatory factor used to induce Treg expansion in future clinical trials of adoptive therapy in type 1 diabetes.

Children with familial hypercholesterolemia have very high total cholesterol and LDL-cholesterol levels in blood which may result in endothelial dysfunction and increase in carotid intima-media thickness. When untreated in childhood, familial hypercholesterolemia is associated with a premature atherosclerotic cardiovascular disease in adulthood. According to the results of clinical studies in children with familial hypercholesterolemia conducted in the last two decades, as well as statements of American Heart Association (AHA), American Academy of Pediatrics (AAP) and Polish Statement called Stanowisko Ekspertów Lipidowych, the recommendations of treatment were published. In children with familial hypercholesterolemia aged 8 years and more statins are one of the first-line medications, thanks to their hypolipemic and pleiotropic activities and well established position in treatment of adult patients with hypercholesterolemia and cardiovascular disease prevention. This paper provides data on pharmacodynamic and pharmacokinetic properties of statins, as well as overview of clinical studies in children with heterozygous familial hypercholesterolemia, regarding efficacy and safety of statins. The studies have revealed significant lowering of LDL cholesterol level (20-50%) and total cholesterol level (20-30%) by statins used in the lowest recommended dose (compared to placebo) in children aged 8 years and more, in a period from 8 weeks to 24 months. In addition to the fact that statin treatment is efficacious, the safety was also confirmed by the meta-analyses of randomized controlled trials in children. The results showed that statin therapy did not impair growth and sexual development in children. The adverse effects were generally mild and did not differ as compared to placebo. However, it should be emphasized that efficacy and safety assessment of statins is limited to 24 months only. Large long-term clinical studies are needed to establish the long-term safety issues of statins in children.

Introduction: Congenital hyperinsulinism of Infancy (CHI) comprises heterogenic defects of insulin secretion with diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacotherapy. The study aimed to establish the first clinical characteristics of Polish patients with CHI and to propose a novel clinical algorithm allowing the prioritisation of genetic and radiology studies, based on patient's characteristics and response to pharmacotherapy., Material and Methods: Thirty-one patients with CHI were recruited from five reference centres in Poland. Clinical and biochemical parameters were statistically evaluated and compared to those of a control group (n = 30)., Results: CHI predisposes to increased birth weight (p = 0.004), lower Apgar score (p = 0.004), perinatal complications (74%), and neurological implications (48%). Diagnostic process and therapy were inconsistent. A trial of pharmacotherapy was applied in 21 patients (68%), and diagnostic imaging with 18F-L-DOPA PET was performed in only 3. Eighteen patients (58%) were surgically treated, including 8 infants (44%) aged less than 2 months. Depending on the type of resection, further hypoglycaemia was observed postoperatively in 50% (n = 9) and hyperglycaemia in 39% (n = 7) of cases. Based on foregoing results, a clinical algorithm was proposed., Conclusions: Standardisation of clinical management with the use of pharmacotherapy, genetic screening, and diagnostic imaging will allow the optimisation of therapy and minimisation of treatment complications.

Introduction: The natural history of type 1 diabetes is concerned with the appearance of autoantibodies against antigens of pancreatic beta cells. The last decade revealed some evidence of the participation of T regulatory lymphocytes - cells which suppress immune response - in the pathogenesis of type 1 diabetes and prediabetes., Aim of the Study: was the assessment of T regulatory cells in the blood of children at risk for developing type 1 the diabetes mellitus., Material and Methods: 85 subjects, siblings of children with type 1 diabetes, were enrolled into the study. The presence of anti-GAD65 antibodies was assessed. With the use of flow cytometry the following cell subpopulations were noted: CD4+, CD4+CD25high and CD4+CD25highCD127low with the coexpression of: CD28, CD45RO, CD54, CD62L and CD134 molecules., Results: We did not observe any differences in white blood cell count, lymphocyte (including CD4+) count and the percentage between the examined and control groups. We noted higher percentages of T regulatory cells: CD4+CD25high, CD4+CD127low and CD4+CD25highCD127low in children with the presence of anti-GAD65 antibodies as compared to the control children., Conclusion: Higher percentages of T regulatory cells in the blood of children with the presence of anti-GAD65 antibodies may suggest an intensive regulatory response present in patients at risk for developing type 1 diabetes.