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OBJECTIVES: We aimed to study the prevalence of the early onset Type 1 diabetes in Slovakia during the years 1996-2017. BACKGROUND: Prevalence of Type 1 diabetes in young children is increasing worldwide. However, recent data from Slovakia are missing. METHODS: All children with newly diagnosed Type 1 diabetes included in the study were diagnosed in the Children Diabetes Centre in Bratislava during the years 1996-2017. The incidence of T1D in children aged below 3 and below 5 years was calculated and compared to the T1D incidence in older children. Incidence trends were calculated with the Poissed regression. RESULTS: Gender-adjusted incidence of T1D annually increased by 5.4 % (CI: 3.9-6.8; p < 0.001) in children <3 years, and by 3.4 % (95 % CI 2.2-4.6; p<0.001) in children <5 years during the last two decades. Moreover, the proportion of young children <3 years of age among all newly diagnosed children and adolescents increased over time (4.2±2.8 % in years 1996-1998; 12.2±5.8 % in years 2004-2008, and 13.7±7.4 % during the years 2013-2017). CONCLUSION: We found a significant increase in the incidence and proportion of T1D in young children during the last two decades. Similar data were also found in other European countries. This could be explained by changing environmental conditions (Fig. 1, Ref. 32). [ABSTRACT FROM AUTHOR]

Objective. Mutations of the KCNJ11 gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have a de-novo mutation. We aimed to compare diabetes phenotype in two children and their mothers with PNDM carrying the same sulfonylurea-sensitive KCNJ11 variants.

MODY (Maturity Onset Diabetes of the Young) is a type of diabetes resulting from a pathogenic effect of gene mutations. Up to date, 13 MODY genes are known. Gene HNF1A is one of the most common causes of MODY diabetes (HNF1A-MODY; MODY3). This gene is polymorphic and more than 1200 pathogenic and non-pathogenic HNF1A variants were described in its UTRs, exons and introns. For HNF1A-MODY, not just gene but also phenotype heterogeneity is typical. Although there are some clinical instructions, HNF1A-MODY patients often do not meet every diagnostic criteria or they are still misdiagnosed as type 1 and type 2 diabetics. There is a constant effort to find suitable biomarkers to help with in distinguishing of MODY3 from Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). DNA sequencing is still necessary for unambiguous confirmation of clinical suspicion of MODY. NGS (Next Generation Sequencing) methods brought discoveries of multiple new gene variants and new instructions for their pathogenicity classification were required. The most actual problem is classification of variants with uncertain significance (VUS) which is a stumbling-block for clinical interpretation. Since MODY is a hereditary disease, DNA analysis of family members is helpful or even crucial. This review is updated summary about HNF1A-MODY genetics, pathophysiology, clinics functional studies and variant classification.

Objectives. Leigh syndrome is a progressive early onset neurodegenerative disease typically presenting with psychomotor regression, signs of brainstem and/or basal ganglia disease, lactic acidosis, and characteristic magnetic resonance imaging findings. At molecular level, deficiency of respiratory complexes and/or pyruvate dehydrogenase complex is usually observed. Nuclear gene SURF1 encodes an assembly factor for cytochrome c-oxidase complex of the respiratory chain and autosomal recessive mutations in SURF1 are one of the most frequent causes of cytochrome c-oxidase-related Leigh syndrome cases. Here, we aimed to elucidate the genetic basis of Leigh syndrome in three Slovak families.

The article addresses the issue of efficiency assessment of the security system (SS) in terms of the Information Security Management System (information resources of the information system in an organization). It is assumed that the purpose of such security system is to achieve a declared level of protection of the information system resources. Therefore, the level of security of information system in a given organization shall be determined by the efficiency assessment of the security system. The efficiency of the security system mainly depends on the functional properties of its components and other factors occurring in its environment. The article mainly focuses on security configuration, i.e. technical configuration and security organization configuration. The thesis was adopted that the efficiency of the security system may be considered as a set-theoretic efficiency sum of the security configurations invoked in such system. Additionally, it was assumed that a prerequisite for the desired measures (indicators) of the efficiency assessment of the SS shall be to propose such measures and develop appropriate ways (methods) of their calculation. The efficiency measure for the SS as well as two methods of efficiency assessment of the SS were proposed in the article.

The article outlines the concept of maintaining the required security level of the information system in the organization (SIO) through appropriate control of the security configurations of the security system. The security system (SS) model was proposed and its basic elements characterized to maintain the current security level of the information resources. The desired current security feature of the SIO shall be obtained by generating appropriate security technical and organizational configurations from the set of permissible solutions. The proposed concept, which takes into account the impact of not only basic security elements of the information resources (e.g. types of resources, security attributes, risks, vulnerability), but also changes in the working conditions of the information system and security system as well as the entire security and quality management environment of the organization, constitutes own proposal of the authors.

J.M. Stanik w swoim artykule pochyla się nad kwestią uchwycenia różnic osobowościowych między przestępcami popełniającymi odmienne rodzaje przestępstw, co umożliwiałoby zrozumienie motywacji działania sprawców. Zdaniem autora jest to nieodzowny element w prawidłowym przeprowadzeniu procesu, wymierzeniu kary i skutecznym przebiegu resocjalizacji. W tekście zostają przedstawione wyniki badań na grupie 129 osób skazanych za pobicia, kradzieże, napady z rabunkiem oraz kradzież z włamaniem, przebywających w półotwartym Zakładzie Karnym w Wojkowicach o rygorze zasadniczym i złagodzonym. Badania przeprowadzono na trzech inwentarzach psychologicznych: IBZO DSM-IV M. Radochońskiego i J.M. Stanika, SABD Bussa-Durkee oraz SUI J.M. Stanika. W tekście został zawarty dokładny opis każdego z powyższych inwentarzy, stanowiący wstęp do analizy wyników badań. Rezultaty przeprowadzanych testów zostały przedstawione w tabelach i ukazują różnice występujące pomiędzy skazanymi popełniającymi wymienione wyżej przestępstwa. W tekście zostaje również przedstawiona interpretacja uzyskanych wyników. Według J.M. Stanika wśród sprawców dokonujących kradzieży i włamań występują: silnie utrwalone postawy nieufności, podejrzliwości oraz negacja wymagań społeczno-prawnych. Z tego powodu zdaniem autora przestępstwa te nie mają charakteru okazjonalnego. Autor odwołuje się również do dysertacji doktorskiej J. Kucharewicz: Psychologiczna analiza procesów motywacyjnych przestępstw popełnionych przez nieletnich, w której zostały przedstawione wyniki badań przeprowadzonych na grupie 36 nieletnich. W podsumowaniu można znaleźć stwierdzenie, że u większości badanych zachowania przestępcze są umotywowane mechanizmami osobowościowymi, a nie zmiennymi sytuacjami.

This study outlines the system risk model of IT system oriented at the safety of the processes of sensitive data processing. The model constitutes a multi-dimensional approach to the analysis of IT system risk and IT processes implemented therein. The presented approach includes various categories of risk factors, resulting from both the architecture of the very IT system, IT security elements and security of the continued operations. The model described in this article may constitute a starting point for the development of the method for IT system risk analysis and appropriate IT security policy, which may in turn constitute input values for the methodology of IT system risk management.

The article discusses the problem of risk management in the context of safety of an organization's information assets. Assuming system of information risk management as a basic element of organization management in the aspect of information safety of modern organizations, this document focuses on methods and techniques of qualitative risk estimates. Basic standards and good practice from areas of risk management and ensuring information safety in the organization were recalled.

Risk is an inherent part of the functioning of every organization therefore the risk management should be a natural activity at each level of management. A common mistake in the management process of an organization is separating the security system, including the risk management system, and treating it as an isolated element. The article presents the place and role of the risk management system in the context of safety of the IT resource of an organization. A model of the risk management system was developed as the basic element of the organization management system and function supporting the continued operation in terms of IT safety of modern organizations.

Aims: The aim is to identify people with HNF1A-MODY among individuals in diabetic cohort solely based on low hs-CRP serum level and early diabetes onset., Methods: In 3537 participants, we analyzed the hs-CRP levels. We analyzed the HNF1A gene in 50 participants (1.4% of the cohort) with type 1 or type 2 diabetes who had hs-CRP ≤0.25 mg/L and were diagnosed with diabetes mellitus (DM) at the age of 8-40 years. We functionally characterized two identified missense variants., Results: Three participants had a rare variant in the HNF1A gene, two of which we classified as likely pathogenic: c.1369&#95;1384dup (p.Val462Aspfs*92) and c.737T>G (p.Val246Gly), and one as likely benign: c.1573A>T (p.Thr525Ser). Our functional studies revealed that p.Val246Gly decreased HNF1α transactivation activity to ~59% and the DNA binding ability to ~16% of the wild-type, while p.Thr525Ser variant showed no effect on transactivation activity, DNA binding, nor nuclear localization. Based on the two identified HNF1A-MODY patients among 3537 people with diabetes, we estimate 0.057% as the minimal HNF1A-MODY prevalence in Slovakia. A positive predictive value of hs-CRP ≤0.25 mg/L for finding HNF1A-MODY individuals was 4.0% (95% CI 0.7%, 13.5%)., Conclusions: Hs-CRP value and age of DM onset could be an alternative approach to current diagnostic criteria with a potential to increase the diagnostic rate of HNF1A-MODY., (© 2023 Diabetes UK.)

Background: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children., Methods: We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-β, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5-80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts., Findings: There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1-3.21)), fasting insulin HR 1.89 (95% CI 1.11-3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62-1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses., Interpretation: The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches., Funding: German Research Foundation (DFG)-through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union-European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03., Competing Interests: MB received honoraria and consulting fees from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis and Sanofi and is part of the advisory board from Boehringer-Ingelheim. All other authors have no conflicts of interest relevant to this article to disclose., (© 2023 The Author(s).)

Little is known about complete remission in Type 1 diabetes mellitus (T1D) with the discontinuance of insulin treatment for a period of time. In this retrospective study we analysed the frequency and factors of onset and duration of 1. remission and 2. complete remission in children and adolescents with T1D from the Children Diabetes Centre in Bratislava, Slovakia. A total of 529 individuals with T1D, aged < 19 years (8.5 ± 4.3 years) at diabetes onset were included in the study. Remission was defined by HbA1c < 7.0% (53 mmol/mol) and an insulin daily dose < 0.5 IU/kg (and 0 IU/kg for complete remission). Remission occurred in 210 (39.7%) participants, and 15 of them had complete remission (2.8% from all participants). We have identified a new independent factor of complete remission onset (higher C-peptide). Complete remitters had a longer duration of remission compared with other remitters and also differed in lower HbA1c levels. No association was seen with autoantibodies or genetic risk score for T1D. Thus, not only partial but also complete remission is influenced by factors pointing toward an early diagnosis of T1D, which is important for better patient outcome., (© 2023. The Author(s).)

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP), regulate growth and metabolic pathways. Here, we asked if serum levels of these factors are altered with overweight/obesity and if this is related to adipose tissue (AT) expression and/or increased fat mass. Furthermore, we hypothesized that expression of GHR, IGF-1 and IGFBP-3 is associated with AT function. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio obesity-related elevations were detectable until early puberty. Circulating levels did not correlate with AT expression of these factors, which was decreased with overweight/obesity. Independent from obesity, expression of GHR, IGF-1 and IGFBP-3 was related to AT dysfunction,and increased insulin levels. Serum GHBP was associated with liver fat percentage and transaminase levels. We conclude that obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased AT mass and elevations in GHBP are more closely related to liver status in children. The diminished AT expression of these factors with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

Skin autofluorescence (SAF) is a noninvasive method reflecting tissue accumulation of advanced glycation end products (AGEs). We investigated whether, in newly diagnosed children and adolescents with type 1 diabetes (T1D), this surrogate marker of long-term glycemia is associated with markers of the early manifestation phase, residual secretion capacity of the ß-cells, and the occurrence of remission. SAF was measured in 114 children and adolescents (age: 8.0 ± 4.5 years, 44% girls) at the time of T1D diagnosis, and related to HbA1c, C-peptide, diabetic ketoacidosis, and remission. 56 patients were followed up for 1 year. Seventy-four sex- and age-matched healthy individuals served as controls. SAF was higher in the T1D group compared with controls (1.0 ± 0.2 vs. 0.9 ± 0.2, p < 0.001). At the time of diagnosis, SAF correlated with HbA1c (r = 0.285, p = 0.002), was similar in patients with and without ketoacidosis, and was lower in the remitters compared with non-remitters (0.95 ± 0.18 vs. 1.04 ± 0.26, p = 0.027). Unlike HbA1c, SAF was an independent predictor of remission (∆R 2 = 0.051, p = 0.004). Former studies consider SAF in diabetic patients as a tool to identify individuals at an increased risk of chronic complications. Here we show that determination of SAF at the time of T1D diagnosis might potentially predict remission, at least in children.

Aims: We previously demonstrated that antennary fucosylated N-glycans on plasma proteins are regulated by HNF1A and can identify cases of Maturity-Onset Diabetes of the Young caused by HNF1A variants (HNF1A-MODY). Based on literature data, we further postulated that N-glycans with best diagnostic value mostly originate from alpha-1-acid glycoprotein (AGP). In this study we analyzed fucosylation of AGP in subjects with HNF1A-MODY and other types of diabetes aiming to evaluate its diagnostic potential., Methods: A recently developed LC-MS method for AGP N-glycopeptide analysis was utilized in two independent cohorts: a) 466 subjects with different diabetes subtypes to test the fucosylation differences, b) 98 selected individuals to test the discriminative potential for pathogenic HNF1A variants., Results: Our results showed significant reduction in AGP fucosylation associated to HNF1A-MODY when compared to other diabetes subtypes. Additionally, ROC curve analysis confirmed significant discriminatory potential of individual fucosylated AGP glycopeptides, where the best performing glycopeptide had an AUC of 0.94 (95% CI 0.90-0.99)., Conclusions: A glycopeptide based diagnostic tool would be beneficial for patient stratification by providing information about the functionality of HNF1A. It could assist the interpretation of DNA sequencing results and be a useful addition to the differential diagnostic process., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Obesity can affect linear growth of children but there is uncertainty regarding the dynamics and potential causes., Methods: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood cohorts (8,629 children, 37,493 measurements), recruited from 1999 to 2018 in Germany, we compared height, growth, and endocrine parameters between normal-weight and children with obesity (0-20 years). Derived from the independent German CrescNet registry (12,703 children) we generated height reference values specific for children with obesity (data collected from 1999 to 2020)., Findings: Children with obesity were significantly taller than normal-weight peers, differing at maximum by 7·6 cm (1·4 height, standard deviation scores or SDS) at age 6-8 years. Already at birth, children with obesity were slightly taller and thereafter had increased growth velocities by up to 1·2 cm/year. This growth acceleration was unrelated to parental height, but was accompanied by increased levels of insulin-like growth factor-1 (IGF-1), insulin and leptin. During puberty, children with obesity showed a catch-down in height SDS. The reduction in pubertal growth velocity by up to 25% coincided with a decrease in levels of IGF-1 (by 17%) and testosterone (by 62%) in boys and estradiol (by 37%) in girls. We confirmed these alterations in growth in the independent CrescNet cohort and furthermore provide height reference values for children with obesity for open access., Interpretation: Dynamics of linear growth are altered distinctively in different developmental phases in children with obesity. Early emergence before other profound comorbidities implies predisposition, environmental, and/or endocrine factors affecting growth in early life. Height reference values for children with obesity may enhance the precision of clinical health surveillance., Funding: German Research Foundation, German Diabetes Association, EU, ESF, ERDF, State of Saxony, ESPE, Hexal, Novo Nordisk, Pfizer Pharma., Competing Interests: Grants for supporting the CrescNet registry are reported by Ruth Gausche. Ruth Gausche reports grants from NovoNordik, grants from Hexal AG, grants from Pfizer, during the conduct of the study. Dr. Körner reports grants from LIFE Child, grants from Childhood Obesity cohort, during the conduct of the study; personal fees from Ipsen Pharma, personal fees from Novo Nordisk, for lecturing outside the submitted work. All the other authors report no conflicts., (© 2021 The Authors.)