Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis.

Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24th March, 2021 to 23rd March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ2(1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations.  Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening. What is Known: • Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances. • Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found. What is New: • TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome. • We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.

Association between interferon-induced helicase (IFIH1) rs1990760 polymorphism and seasonal variation in the onset of type 1 diabetes mellitus.

BACKGROUND: Infections, mostly of viral origin, may contribute to the seasonal variation in the onset of type 1 diabetes mellitus (T1DM). The rs1990760 (A>G, Ala946Thr) polymorphism (GG genotype) of the interferon induced helicase (IFIH1), a virus recognition receptor, confers a modest protection for T1DM. The aim of our study was to evaluate a possible association between this IFIH1 polymorphism and the seasonal variation in the onset of T1DM. MATERIALS AND METHODS: The IFIH1 rs1990760 polymorphism was genotyped in 1055 patients of Central-Eastern European ancestry with T1DM (median age at diagnosis: 8.2 [interquartile range, IQR 4.8-11.8] years). T1DM onset was recorded in monthly intervals. RESULTS: The IFIH1 genotype distribution was the following: 436 patients (41.3%) had AA genotype, 483 patients (45.8%) had AG genotype, and 136 patients (12.9%) had GG genotype. Significant seasonal variation in manifestation of T1DM (highest rate in winter and lowest rate in summer period) was observed in the total cohort (n = 1055), irrespective of gender. The disease predisposing AA genotype was more frequently found among new cases with onset in summer vs in those with onset in winter (44.3% vs 37.9%); conversely, the protective GG genotype was less frequent (9.3% vs 12.9%, respectively; P = .0268 for trend). Significant effect of genotype (P = .0418) was found on the seasonal variability of T1DM onset in the total cohort. CONCLUSIONS: The IFIH1 rs1990760 polymorphism seems to be associated with the seasonal manifestation of T1DM. Our findings suggest that this virus receptor gene may contribute to T1DM manifestation primarily in the summer period.

Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry.

OBJECTIVE: To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D). METHODS: An international cross-sectional study including 23 026 T1D children (2-18 years, duration of diabetes ≥1 year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS < -2SD), OW (+1SD < BMI-SDS ≤ +2SD), and obese (OB) (BMI-SDS > +2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes. RESULTS: The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean ± SEM: 0.54 ± 0.05 vs 0.40 ± 0.05, P < 0.0001). In males, BMI-SDS significantly decreased by age (P < 0.0001) in the first three age categories 0.61 ± 0.06 (2 to <10 years), 0.47 ± 0.06 (10 to <13 years), 0.34 ± 0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P < 0.0001): 0.54 ± 0.04 (2 to <10 years), 0.39 ± 0.04 (10 to <13 years), 0.55 ± 0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2 years: 0.38 ± 0.05, 2 to <5 years: 0.44 ± 0.05, and ≥5 years: 0.50 ± 0.05, P < 0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20% ± 0.10% vs 8.06% ± 0.10%, P < 0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups. CONCLUSIONS: The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D.

[Clinical application of the electric cardiometry based non-invasive ICON® hemodynamic monitor]. / Az ICON® elektromos kardiometrián alapuló nem invazív hemodinamikai monitor használata a klinikumban.

Establishment of a proper hemodynamic monitoring system in order to achieve optimal care among critically ill patients is fundamental. In contrast to invasive patient-checking systems, which were introduced decades ago and used in both adult and pediatric intensive care, the non-invasive methods have become more popular in recent years due to technical advancements in intensive care and patient monitoring. This increase in popularity can be attributed to the higher degree of safety and reduced complication rates as well as to its being more economical. Our summary focuses on the ICON® patient monitoring system. This newly engineered, non-invasive tool is based on electrical cardiometry, and uses hemodynamic parameters in both neonatal and pediatric care as well as in adults. The operating principle is simple: the conductivity of the blood in the aorta shows time-dependent changes. Prior to the opening of the aortic valve, the orientation of the red blood cells (RBCs) is random, and it is not until the contraction of the aorta that the RBCs and the opening of the aortic valve achieve a parallel position. The tool senses the conductivity between four placed electrodes, and measures the stroke volume (SV) and cardiac output (CO), before calculating other additional parameters (eg.: systemic vascular resistance) by tracing the variation of bioimpedance according to changes in the heart cycle. The most important advantages of ICON® are the measurements that are made available immediately as well as continuously, and the low complication rate that originates from its non-invasive operation. ICON® is a new, promising hemodynamic device in the tool belt of intensive care. Due to the nature of the device, it is possible to evaluate the status of the patient on a continuous basis, allowing for optimal care. To identify the more accurate clinical indications further measures will be necessary. Orv Hetil. 2018; 159(44): 1775-1781.

Factors influencing antimicrobial resistance and outcome of Gram-negative bloodstream infections in children.

OBJECTIVE: The aim of this study was to collect data about pediatric Gram-negative bloodstream infections (BSI) to determine the factors that influence multidrug resistance (MDR), clinical course and outcome of children affected by Gram-negative sepsis. METHODS: In this observational, prospective, multicenter study we collected cases of pediatric Gram-negative BSI during a 2-year period. We analyzed epidemiological, microbiological and clinical factors that associated with acquisition of MDR infections and outcome. RESULTS: One-hundred and thirty-five BSI episodes were analyzed. Median age of children was 0.5 years (IQR 0.1-6.17, range 0-17 years). Predominant bacteria were Enterobacteriaceae (68.3 %), and Pseudomonas spp. (17.9 %). Multidrug resistance was detected in 45/134 cases (33.6 %), with the highest rates in Escherichia coli, Enterobacter and Pseudomonas spp. Acquisition of MDR pathogens was significantly associated with prior cephalosporin treatment, older age, admission to hemato-oncology unit, polymicrobial infections, higher rate of development of septic shock, and multiple organ failures. All-cause mortality was 17.9 %. Presence of septic shock at presentation and parenteral nutrition were associated with higher mortality. Pseudomonas spp., and Enterobacter spp. BSIs had the highest rate of mortality. Inappropriate empiric antibiotic therapy was more frequent in MDR patients, although not significantly associated with poor outcome. CONCLUSION: Rates of multidrug resistance and mortality in children with Gram-negative bloodstream infections remain high in our settings. Empiric broad-spectrum antibiotics and combination therapy could be recommended, especially in children with malignant diseases, patients admitted to the PICU, and for cases with septic shock, who have higher mortality risk.

Evaluation of an open access software for calculating glucose variability parameters of a continuous glucose monitoring system applied at pediatric intensive care unit.

BACKGROUND: Continuous Glucose Monitoring (CGM) has become an increasingly investigated tool, especially with regards to monitoring of diabetic and critical care patients. The continuous glucose data allows the calculation of several glucose variability parameters, however, without specific application the interpretation of the results is time-consuming, utilizing extreme efforts. Our aim was to create an open access software [Glycemic Variability Analyzer Program (GVAP)], readily available to calculate the most common parameters of the glucose variability and to test its usability. METHODS: The GVAP was developed in MATLAB® 2010b environment. The calculated parameters were the following: average area above/below the target range (Avg. AUC-H/L); Percentage Spent Above/Below the Target Range (PATR/PBTR); Continuous Overall Net Glycemic Action (CONGA); Mean of Daily Differences (MODD); Mean Amplitude of Glycemic Excursions (MAGE). For verification purposes we selected 14 CGM curves of pediatric critical care patients. Medtronic® Guardian® Real-Time with Enlite® sensor was used. The reference values were obtained from Medtronic®(')s own software for Avg. AUC-H/L and PATR/PBTR, from GlyCulator for MODD and CONGA, and using manual calculation for MAGE. RESULTS: The Pearson and Spearman correlation coefficients were above 0.99 for all parameters. The initial execution took 30 minutes, for further analysis with the Windows® Standalone Application approximately 1 minute was needed. CONCLUSIONS: The GVAP is a reliable open access program for analyzing different glycemic variability parameters, hence it could be a useful tool for the study of glycemic control among critically ill patients.

The Impact of Parental Electronic Health Literacy on Disease Management and Outcomes in Pediatric Type 1 Diabetes Mellitus: Cross-Sectional Clinical Study.

BACKGROUND: Despite the growing uptake of smart technologies in pediatric type 1 diabetes mellitus (T1DM) care, little is known about caregiving parents' skills to deal with electronic health information sources. OBJECTIVE: We aimed to assess the electronic health literacy of parents caring for children with T1DM and investigate its associations with disease management and children's outcomes. METHODS: A cross-sectional survey was performed involving 150 parent-child (8-14 years old with T1DM) dyads in a university pediatric diabetology center. Parents' electronic health literacy (eHealth Literacy Scale [eHEALS]), general health literacy (Chew questionnaire and Newest Vital Sign [NVS]), and attitudes toward T1DM care (Parental Self-Efficacy Scale for Diabetes Management [PSESDM] and Hypoglycemia Fear Survey [HFS]) were investigated. Children's treatment, HbA1c level, and quality of life (Pediatric Quality of Life Inventory Diabetes Module [PedsQL Diab] and EQ-5D-Y-3L) were assessed. Multiple linear regression analysis was performed to investigate the determining factors of 6-month average HbA1c. RESULTS: Of the 150 children, 38 (25.3%) used a pen, 55 (36.7%) used a pen plus a sensor, 6 (4.0%) used an insulin pump, and 51 (34.0%) used an insulin pump plus a sensor. Parents' average eHEALS score (mean 31.2, SD 4.9) differed significantly by educational level (P=.04) and the children's treatment (P=.005), being the highest in the pump + sensor subgroup. The eHEALS score showed significant Pearson correlations with the Chew score (r=-0.45; P<.001), NVS score (r=0.25; P=.002), and PSESDM score (r=0.35; P<.001) but not with the children's HbA1c (r=-0.143; P=.08), PedsQL Diab (r=-0.0002; P>.99), and EQ-5D-Y-3L outcomes (r=-0.13; P=.12). Regression analysis revealed significant associations of the child's HbA1c level with sex (ß=0.58; P=.008), treatment modality (pen + sensor: ß=-0.66; P=.03; pump + sensor: ß=-0.93; P=.007), and parents' self-efficacy (PSESDM; ß=-0.08; P=.001). CONCLUSIONS: Significantly higher parental electronic health literacy was found in T1DM children using a glucose sensor. The electronic health literacy level was associated with parents' diabetes management attitude but not with the child's glycemic control. Studies further investigating the role of parental electronic health literacy in T1DM children managed at different levels of care and the local context are encouraged.

[Role of continuous subcutaneous glucose monitoring in intensive care]. / A folyamatos szubkután glükózmonitorizálás szerepe az intenzív terápiában.

Critical care associated with stress hyperglycaemia has gained a new view in the last decade since the demonstration of the beneficial effects of strong glycaemic control on the mortality in intensive care units. Strong glycaemic control may, however, induce hypoglycaemia, resulting in increased mortality, too. Pediatric population has an increased risk of hypoglycaemia because of the developing central nervous system. In this view there is a strong need for close monitoring of glucose levels in intensive care units. The subcutaneous continuous glucose monitoring developed for diabetes care is an alternative for this purpose instead of regular blood glucose measurements. It is important to know the limitations of subcutaneous continuous glucose monitoring in intensive care. Decreased tissue perfusion may disturb the results of subcutaneous continuous glucose monitoring, because the measurement occurs in interstitial fluid. The routine use of subcutaneous continuous glucose monitoring in intensive care units is not recommended yet until sufficient data on the reliability of the system are available. The Medtronic subcutaneous continuous glucose monitoring system is evaluated in the review partly based on the authors own results.

Anti-SARS-CoV-2 Seropositivity Among Children With Newly Diagnosed Type 1 Diabetes Mellitus: A Case-Control Study.

A sudden increase in the number of children with newly diagnosed type 1 diabetes mellitus (T1DM) was experienced during the third wave of COVID-19 epidemic in Hungary. The newly diagnosed T1DM patients had a significantly higher rate of anti-SARS-CoV-2 positivity as compared to prevalent T1DM children [OR (95% CI) 3.74 (1,08,13.55); P=0.04]. The relationship between SARS-CoV-2 infection and diabetes needs to be investigated further.

The Predictive Role of Cognitive Emotion Regulation of Adolescents with Chronic Disease and Their Parents in Adolescents' Quality of Life: A Pilot Study.

BACKGROUND: The purpose of this study was to investigate cognitive emotion regulation in adolescents with chronic illness and their parents. METHODS: Eighty-five young people (mean = 15.86 years, standard deviation = ± 1.42, girls 65.88%) with chronic illnesses (inflammatory bowel disease n = 40 or type 1 diabetes n = 45), and their parents (mean = 46.06 years, 87.06% mother) completed the Cognitive Emotion Regulation Questionnaire (CERQ) for themselves and the Inventory of Quality of Life in Children and Adolescents (ILC) questionnaire adolescent and parent version. We conducted two hierarchical linear regression analyses with "enter" method. The CERQ scales and the diagnosis of chronic disease were chosen as independent variables, and the total ILC score in the first analysis and the ILC proxy score in the second analysis were chosen as dependent variables. RESULTS: Among adolescents, cognitive emotion regulation strategies such as self-blame, positive reappraisal, and catastrophizing have been proven to be predictors of their own quality of life; however, parental self-blame was also found to be a predictor of adolescents' quality of life. Parental rumination and positive refocusing have been shown to be predictors of how parents rate their child's quality of life. CONCLUSIONS: The present study sheds light on cognitive emotion regulation strategies in adolescents with chronic illness and their parents that have a significant impact on the development of young people's quality of life.

Starving for independence. Anorexia nervosa in an adolescent with type 1 diabetes / Önállóságra éhezve. Az 1-es típusú diabetes mellitus és az anorexia nervosa együttes elofordulása egy serdülo leányban.

Összefoglaló. Az 1-es típusú diabetes mellitus (T1DM-) betegek körében az evészavarok elofordulása az átlagpopulációhoz képest körülbelül kétszeresre teheto. Ez a komorbiditás különösen veszélyes mind a magas mortalitási rizikó, mind a súlyos szövodmények lehetosége miatt. Az evészavarban szenvedo, T1DM-mel élo gyermekek és fiatalok hatékony kezelése a diabetológusok, pszichiáterek, pszichológusok, novérek és dietetikusok összehangolt munkájával valósítható meg. Közleményünkben egy 14,5 éves, T1DM-mel élo, anorexia nervosával diagnosztizált páciensünk multidiszciplináris terápiáját mutatjuk be, kiemelve a különbözo szakemberek együttmuködésének fobb metszéspontjait. A szoros diabetológiai gondozással párhuzamosan az anorexia nervosa terápiájában a protokollok ajánlásaival megegyezoen családterápiát és kognitív viselkedésterápiás elemekkel bovített egyéni terápiát alkalmaztunk. A terápiás folyamat összesen 18 hónapig tartott. Esetünk korábban le nem írt diabetológiai érdekessége, hogy a számottevo súlycsökkenéssel párhuzamosan betegünk inzulinigénye a töredékére csökkent, ami jelentos mértékben érintette a bazálisinzulin-szükségletet is. Orv Hetil. 2021; 162(33): 1341-1346. Summary. The incidence of eating disorders is approximately twice as high in type 1 diabetes mellitus (T1DM) compared to the general population. Comorbidity is related to potentially severe organ complications and consequently higher mortality risk. The effective treatment of eating disorders in T1DM is provided by the teamwork of diabetologists, psychiatrists, psychologists, nurses and dietitians. The purpose of this paper is to present the multidisciplinary treatment of a 14.5-year-old adolescent with T1DM and diagnosed with anorexia nervosa, focusing on the cooperation of the professionals. In line with the current guidelines, both family therapy and cognitive behavioral therapy-informed individual psychotherapy were applied beside the strict diabetes control. Her therapy process lasted 18 months. The unusual diabetological aspect of our case is that the significant weight loss was associated with highly decreased insulin requirement affecting also the basal insulin requirements. Orv Hetil. 2021; 162(33): 1341-1346.

Transitional elevation of anti-tissue transglutaminase antibodies in children with type 1 diabetes mellitus without coeliac disease / A szöveti antitranszglutamináz átmeneti emelkedése coeliakiával nem társult I-es típusú cukorbeteg gyermekekben.

Összefoglaló. Bevezetés: Az 1-es típusú diabetes mellitus és a coeliakia gyakori társulása jól ismert. Néhány tanulmány beszámol átmeneti antitranszglutamináz-emelkedésrol 1-es típusú diabeteses betegekben, akiknél az emelkedett antitestszint gluténmentes diéta bevezetése nélkül normalizálódik. Célkituzés: Kutatásunk során az átmeneti antitranszglutamináz-emelkedés gyakoriságának meghatározását tuztük ki célul. További célunk volt a coeliakia gyakoriságának megállapítása 1-es típusú diabetesszel gondozott betegeink között. Módszer: A Semmelweis Egyetem I. Gyermekgyógyászati Klinikáján 1-es típusú diabetesszel gondozott betegeket vontuk be vizsgálatunkba (238 lány, 265 fiú, medián [IR] életkor az 1-es típusú diabetes diagnózisakor: 7,83 [4,67-11] év). Vizsgáltuk a jelenség idobeli megjelenését, az emelkedés mértékét, gyakoriságát és az antitest típusát. Leíró statisztikai módszereket és khi-négyzet-próbát alkalmaztunk. Eredmények: A vizsgált populációban a coeliakia gyakorisága 12,52%. Átmeneti antitranszglutamináztiter-emelkedést 48 gyermeknél (10,9%) észleltünk. Összesen 71-szer mértünk átmeneti antitranszglutamináz-emelkedést. A gyermekek közül 34 esetben (70,83%) egyszer fordult elo emelkedést mutató antitest, a többi betegnél 2-8 alkalommal. Gyakrabban tapasztaltunk izolált IgA-típusú emelkedést, mint izolált IgG-típusút (54 vs. 5). Következtetés: Az átmeneti antitranszglutamináz-emelkedés gyakorisága magas, összevetheto a valódi coeliakiás csoporttal. Kutatásunk alátámasztja a nemzetközi ajánlást, miszerint mérsékelt mértéku antitranszglutamináz-emelkedés esetén, tünetmentes 1-es típusú diabetesszel gondozott betegben a gluténfogyasztás folytatása és az antitestszintek gyakori kontrollja javasolt. Orv Hetil. 2021; 162(48): 1924-1930. INTRODUCTION: The frequent association of type 1 diabetes mellitus with coeliac disease is well known. Development of transitional elevation of anti-tissue transglutaminase antibodies in the diagnosis of type 1 diabetes is reported in some studies. In these cases, the anti-tissue transglutaminase antibodies returned to normal without gluten-free diet. OBJECTIVE: Our aim was to assess the frequency of transitional elevation of anti-tissue transglutaminase in our type 1 diabetes patients. We aimed to investigate the prevalence of coeliac disease in patients with type 1 diabetes. METHOD: Patients with type 1 diabetes at the Ist Department of Paediatrics, Semmelweis University, were enrolled in the study (238 girls, 265 boys; the median age at the time of type 1 diabetes diagnosis was 7.83 [4.67-11] years). Descriptive statistical analysis was done and the time of appearance, extent, frequency and type of elevated anti-tissue transglutaminase antibodies were examined. RESULTS: The proportion of children with diagnosed coeliac disease was 12.52%. We detected transitional anti-tissue transglutaminase elevation in 48 cases (10.9%). Temporarily elevated antibody levels were measured 71 times. In 34 children (70.83%), the temporary elevation occured once, while in the others, antibody levels became positive 2-8 times. The elevation of the IgA antibody was more frequent than the elevation of the IgG antibody (54 vs. 5). CONCLUSION: The frequency of temporary elevated anti-tissue transglutaminase levels is considered high. Our study confirms the recommendation that in the case of moderate anti-tissue transglutaminase levels with lack of clinical symptoms, control antibody measurement is necessary with ongoing gluten consumption. Orv Hetil. 2021; 162(48): 1924-1930.

A Comprehensive Analysis of Hungarian MODY Patients-Part I: Gene Panel Sequencing Reveals Pathogenic Mutations in HNF1A, HNF1B, HNF4A, ABCC8 and INS Genes.

Maturity-onset diabetes of the young (MODY) has about a dozen known causal genes to date, the most common ones being HNF1A, HNF4A, HNF1B and GCK. The phenotype of this clinically and genetically heterogeneous form of diabetes depends on the gene in which the patient has the mutation. We have tested 450 Hungarian index patients with suspected MODY diagnosis with Sanger sequencing and next-generation sequencing and found a roughly 30% positivity rate. More than 70% of disease-causing mutations were found in the GCK gene, about 20% in the HNF1A gene and less than 10% in other MODY-causing genes. We found 8 pathogenic and 9 likely pathogenic mutations in the HNF1A gene in a total of 48 patients and family members. In the case of HNF1A-MODY, the recommended first-line treatment is low dose sulfonylurea but according to our data, the majority of our patients had been on unnecessary insulin therapy at the time of requesting their genetic testing. Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of the MODY subtype in order to choose the most appropriate treatment.

A Comprehensive Analysis of Hungarian MODY Patients-Part II: Glucokinase MODY Is the Most Prevalent Subtype Responsible for about 70% of Confirmed Cases.

MODY2 is caused by heterozygous inactivating mutations in the glucokinase (GCK) gene that result in persistent, stable and mild fasting hyperglycaemia (5.6-8.0 mmol/L, glycosylated haemoglobin range of 5.6-7.3%). Patients with GCK mutations usually do not require any drug treatment, except during pregnancy. The GCK gene is considered to be responsible for about 20% of all MODY cases, transcription factors for 67% and other genes for 13% of the cases. Based on our findings, GCK and HNF1A mutations together are responsible for about 90% of the cases in Hungary, this ratio being higher than the 70% reported in the literature. More than 70% of these patients have a mutation in the GCK gene, this means that GCK-MODY is the most prevalent form of MODY in Hungary. In the 91 index patients and their 72 family members examined, we have identified a total of 65 different pathogenic (18) and likely pathogenic (47) GCK mutations of which 28 were novel. In two families, de novo GCK mutations were detected. About 30% of the GCK-MODY patients examined were receiving unnecessary OAD or insulin therapy at the time of requesting their genetic testing, therefore the importance of having a molecular genetic diagnosis can lead to a major improvement in their quality of life.

Celiac disease in children with type 1 diabetes varies around the world: An international, cross-sectional study of 57 375 patients from the SWEET registry.

BACKGROUND: Children with type 1 diabetes (T1D) are at much higher risk of developing celiac disease (CD) than the general population. The aim of the study was to assess the prevalence and differences in clinical presentation of CD in T1D in different regions of the world. METHODS: This study is based on the Better control in Pediatric and Adolescent diabeteS: Working to crEate cEnTers of Reference (SWEET) database. There were 57 375 patients included in the study, aged ≤18 years from 54 SWEET centers. Only centers with screening for celiac disease were included. Regression models adjusted for age, diabetes duration, and gender and a fixed effect in the models for region was used. Diabetes duration, age at diabetes onset, and sex were presented as unadjusted results. RESULTS: CD was present in 2652 subjects (4.5%), with different prevalence among regions: from 1.9% in Asia/Middle East to 6.9% in Australia/New Zealand. CD was observed more often among females. Comparing children with and without CD, characteristics for those with CD were younger age at diabetes onset (6.3 [3.3; 9.8] vs 8.1 [4.6; 11.3], P < 0.001) and had longer diabetes duration (6.4 [3.6; 9.8] vs 4.8 [2.1; 8.2], P < 0.001). Further, they had lower glycosylated hemoglobin (HbA1c) in Europe and North America/Canada; lower body mass index (BMI)-SD score (BMI-SDS) in southern Europe, North America, and Canada; In most regions daily insulin dose was lower, height-SDS was lower, and the percentage of insulin pump users was higher in children with T1D and CD. CONCLUSIONS: The prevalence and the anthropometric and metabolic consequences of CD in children with T1D differ around the world.

[Changes of lactate levels in diabetic ketoacidosis and in newly diagnosed type 1 diabetes mellitus]. / Laktátszintváltozások diabeteses ketoacidosisban és frissen diagnosztizált 1-es típusú diabetes mellitusban.

Introduction: It is known that lactate concentration is increased in diabetic ketoacidosis (DKA), however, the pathophysiology and kinetics of lactate changes are still unclear. Normally, L-lactate is the major form in the human body. According to previous data, also D- and L-lactate might be increased in hyperglycaemic disorders. Aim: We aimed to describe the kinetics and mechanisms of lactate concentration changes in ketoacidosis and newly diagnosed diabetes. Method: We performed a prospective study, including 5-18-year-old children with ketoacidosis (DKA, n = 13) and with newly diagnosed type 1 diabetes without ketoacidosis (T1DM, n = 6). We performed routine blood gas analysis 0-12-24-48 hours after admission, which also measured L-lactate levels. We also determined total venous serum lactate level by gas chromatography-mass spectrometry. Results: Initial plasma lactate concentration was increased in ketoacidosis as compared to the newly diagnosed diabetes group (p<0.05). After 12 h of rehydration, lactate levels were greatly reduced in ketoacidotic patients but after 24-48 h it was repeatedly increased (all p<0.01). In the 0-12 h phase, total serum lactate level was higher than L-lactate level, referring to D-lactate production. Conclusion: We described two L-lactate peaks in ketoacidosis. In the first 12 hours anaerobic glycolysis seems to have major role in hyperlactataemia. We assume that stimulated aerobic glycolysis leads to the second lactate peak. However, D-lactate is not routinely measured, it may contribute to the initial hyperlactataemia in both groups and is comparable to L-lactate production in ketoacidosis. Orv Hetil. 2019; 160(45): 1784-1790.

[Incidence of thyroid autoimmunity in children with type 1 diabetes mellitus]. / Pajzsmirigy-autoimmunitás elôfordulása 1-es típusú diabéteszes gyermekekben.

UNLABELLED: It is well known that patients suffering from an autoimmune disease are more prone to develop another one, too. The authors have previously shown frequent occurrence of celiac disease in patients with type 1 diabetes mellitus compared to the background population. Autoimmune thyroid disease, the most common autoimmune disease associated with type 1 diabetes mellitus, generally occurs after the manifestation of diabetes, in the second decade of life. The aim of the study was to investigate the prevalence of thyroid autoimmunity as well as the frequency of autoimmune thyroid disease in patients with type 1 diabetes mellitus. Their aim was also to compare the prevalence of autoimmune thyroid disease in patients with type 1 diabetes mellitus and in those with type 1 diabetes mellitus and celiac disease. METHODS: Screening was performed in 268 patients with type 1 diabetes mellitus alone and in 48 children with type 1 diabetes mellitus and celiac disease, with anti-peroxidase and anti thyroglobulin antibody. In case of autoantibody positivity, testing thyroid function and ultrasonography confirmed the autoimmune thyroid disease. According to the results, frequency of autoantibody positivity was significantly higher in diabetic patients suffering from celiac disease (type 1 diabetes mellitus: 43 (16%), type 1 diabetes mellitus + celiac disease: 16 (33,3%), p < 0,01). Hypothyroidism due to thyroiditis was also more prevalent in patients with type 1 diabetes mellitus and celiac disease. CONCLUSIONS: Due to increased risk, the authors emphasise the need of frequent screening for autoimmune thyroid disorder in patients with type 1 diabetes mellitus and celiac disease.