Potential Role of Selected miRNAs in the Pathogenesis of Autoimmune Thyroid Diseases in Children and Adolescents.

BACKGROUND: Many epigenetic factors, including microRNAs, are involved in the process of changing gene expressions. Small non-coding RNA molecules, called miRNAs, are responsible for regulating gene translation by silencing or degrading target mRNAs. It is acknowledged that for many diseases, they may be novel diagnostic and prognostic biomarkers. Patients with autoimmune thyroid diseases are more likely to develop nodules in the thyroid tissue, and Hashimoto's thyroiditis and Graves' disease predispose patients to thyroid cancer. We evaluated the concentrations of microRNA molecules (miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p, miR-150-5p) in the blood of children with thyroid disorders. In addition, we wished to identify molecules whose change in concentration predisposes to the development of thyroid cancer. AIM: The aim of this study is to evaluate selected epigenetic elements by analyzing the levels of miR-15a-5p, miR-126-3p, miR-142-5p, miR-150-5p and miR-21-5p in the blood of pediatric patients with Graves' disease (n = 25), Hashimoto's thyroiditis (n = 26) and thyroid nodular disease (n = 20) compared to a control group of healthy children (n = 17). MATERIALS AND METHODS: The study consists of groups of children and adolescents aged 10-18 years with autoimmune thyroid disease, with thyroid nodular disease compared to a control group. The miR-15a-5p, miR-126-3p, miR-142-5p, miR-21-5p and miR-150-5p molecules were determined through an immunoenzymatic assay using BioVendor reagents. RESULTS: There is a statistically significant decrease in the expression of the miR-15a-5p in children with Graves' disease (21.61 vs. 50.22 amol/µL, p = 0.03) and in patients with thyroid nodular disease compared to controls (20.23 vs. 50.22 amol/µL, p = 0.04). Higher levels of the miR-142-5p molecule are found in patients with thyroid disease (with GD-3.8 vs. 3.14 amol/µL, p = 0.01; with HT-3.7 vs. 3.14 amol/µL, p = NS, with thyroid nodular disease-4.16 vs. 3.14 amol/µL, p = 0.04). Lower levels of miR-126-3p were noted in the GD group compared to the control group (7.09 vs. 7.24 amol/µL, p = 0.02). No statistically significant changes in the expressions of miR-150-5p and miR-21-5p molecules were observed in the study groups. CONCLUSIONS: 1. The overexpression of the miR-142-5p molecule occurs in children and adolescents with thyroid diseases. 2. Decreased blood levels of miR-15a-5p predispose patients to the formation of focal lesions in the thyroid gland. 3. Identifying a lower expression of the miR-126-3p molecule in the blood of children with GD requires careful follow-up for the development of focal lesions in the thyroid gland and evaluation for their potential malignancy.

Prevalence of Selected Polymorphisms of Il7R, CD226, CAPSL, and CLEC16A Genes in Children and Adolescents with Autoimmune Thyroid Diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are common autoimmune endocrine disorders in children. Studies indicate that apart from environmental factors, genetic background significantly contributes to the development of these diseases. This study aimed to assess the prevalence of selected single-nucleotide polymorphisms (SNPs) of Il7R, CD226, CAPSL, and CLEC16A genes in children with autoimmune thyroid diseases. We analyzed SNPs at the locus rs3194051, rs6897932 of IL7R, rs763361 of CD226, rs1010601 of CAPSL, and rs725613 of CLEC16A gene in 56 HT patients, 124 GD patients, and 156 healthy children. We observed significant differences in alleles IL7R (rs6897932) between HT males and the control group (C > T, p = 0.028) and between all GD patients and healthy children (C > T, p = 0.035) as well as GD females and controls (C > T, p = 0.018). Moreover, the C/T genotype was less frequent in GD patients at rs6897932 locus and in HT males at rs1010601 locus. The presence of the T allele in the IL7R (rs6897932) locus appears to have a protective effect against HT in males and GD in all children. Similarly, the presence of the T allele in the CAPSL locus (rs1010601) seems to reduce the risk of HT development in all patients.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.

Not Only Metabolic Complications of Childhood Obesity.

The increasing incidence of obesity in the pediatric population requires attention to its serious complications. It turns out that in addition to typical, well-known metabolic complications, obesity as a systemic disease carries the risk of equally serious, although less obvious, non-metabolic complications, such as cardiovascular diseases, polycystic ovary syndrome, chronic kidney disease, asthma, thyroid dysfunction, immunologic and dermatologic conditions, and mental health problems. They can affect almost all systems of the young body and also leave their mark in adulthood. In addition, obesity also contributes to the exacerbation of existing childhood diseases. As a result, children suffering from obesity may have a reduced quality of life, both physically and mentally, and their life expectancy may be shortened. It also turns out that, in the case of obese pregnant girls, the complications of obesity may also affect their unborn children. Therefore, it is extremely important to take all necessary actions to prevent the growing epidemic of obesity in the pediatric population, as well as to treat existing complications of obesity and detect them at an early stage. In summary, physicians treating a child with a systemic disease such as obesity must adopt a holistic approach to treatment.

Role of miRNA in Cardiovascular Diseases in Children-Systematic Review.

The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.

Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.

The clinical spectrum of thyrotropin receptor-mediated (TSHR-mediated) diseases varies from loss-of-function mutations causing congenital hypothyroidism to constitutively active mutations (CAMs) leading to nonautoimmune hyperthyroidism (NAH). Variation at the TSHR locus has also been associated with altered lipid and bone metabolism and autoimmune thyroid diseases. However, the extrathyroidal roles of TSHR and the mechanisms underlying phenotypic variability among TSHR-mediated diseases remain unclear. Here we identified and characterized TSHR variants and factors involved in phenotypic variability in different patient cohorts, the FinnGen database, and a mouse model. TSHR CAMs were found in all 16 patients with NAH, with 1 CAM in an unexpected location in the extracellular leucine-rich repeat domain (p.S237N) and another in the transmembrane domain (p.I640V) in 2 families with distinct hyperthyroid phenotypes. In addition, screening of the FinnGen database revealed rare functional variants as well as distinct common noncoding TSHR SNPs significantly associated with thyroid phenotypes, but there was no other significant association between TSHR variants and more than 2,000 nonthyroid disease endpoints. Finally, our TSHR M453T-knockin model revealed that the phenotype was dependent on the mutation's signaling properties and was ameliorated by increased iodine intake. In summary, our data show that TSHR-mediated disease risk can be modified by variants at the TSHR locus both inside and outside the coding region as well as by altered TSHR-signaling and dietary iodine, supporting the need for personalized treatment strategies.

Cytogenetic findings in Polish patients with suspected Fanconi anemia.

BACKGROUND: The high sensitivity of cells of Fanconi anemia (FA) patients to DNA cross-linking agents (clastogens), such as mitomycin C (MMC), was used as a screening tool in Polish children with clinical suspicion of FA. OBJECTIVES: The aim of the study was to compare chromosome fragility between 3 groups, namely non-FA, possible mosaic FA and FA patients. MATERIAL AND METHODS: The study included 100 children with hematological manifestations and/or congenital defects characteristic of FA, and 100 healthy controls. Blood samples obtained from participants were analyzed using an MMC-induced chromosomal breakage test. RESULTS: Patients with clinical suspicion of FA were divided into 3 subgroups based on the MMC test results, namely FA, possible mosaic FA and non-FA. Thirteen out of 100 patients had a true FA cellular phenotype. The mean value of MMC-induced chromosome breaks/cell for FA patients was higher than for non-FA patients (6.67 ±3.92 compared to 0.23 ±0.18). In addition, the percentage of cells with spontaneous aberrations was more than 9 times higher in FA patients than in non-FA patients. CONCLUSIONS: Our results confirmed that the MMC sensitivity test distinguishes between individuals affected by FA, those with possible somatic mosaicism, and patients with bone marrow failure for other reasons, who were classified as non-FA in the first diagnostic step. However, a definitive differential diagnosis requires follow-up mutation testing and chromosome breakage analysis of skin fibroblasts.

Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry.

CONTEXT: The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD). OBJECTIVE: This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1. METHODS: Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor. RESULTS: In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01. CONCLUSION: Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.

Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland.

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.

Determinants Related to Oxidative Stress Parameters in Pediatric Patients with Type 1 Diabetes Mellitus.

Adequate glycemic management is one of the main goals in treating type 1 diabetes mellitus (T1DM) and preventing the early onset of diabetic complications. Improperly controlled diabetes mellitus (DM) will result in oxidative stress (OS) and lead to further related health issues. Therefore, the aim of this study was to evaluate the body's ability to defend against OS depending on the duration of T1DM, metabolic management, antioxidant intake and modern glycemic monitoring systems (GMS). The study included 103 adolescents with T1DM aged 10-17 years. The control group consisted of 65 healthy peers. The patients' blood was assayed for antioxidant enzymes, minerals and toxic elements. In addition, their dietary intake of antioxidant components was assessed. The T1DM group had higher total oxidant status, oxidative stress index and Cu/Zn ratio values, higher concentrations of malondialdehyde and lower total antioxidant status (TAS) and chromium, zinc, superoxide dismutase and catalase levels than their healthy peers. The comparison between GMS types revealed favorable changes in OS parameters for the flash and continuous systems. Furthermore, an effect of vitamin A and C dietary intake on serum TAS concentrations was detected. More than 82% of the patients with high TAS fulfilled the estimated average requirement norm for vitamin A, and more than 60% fulfilled the vitamin C requirement. In youths with T1DM, it is advisable to observe the antioxidant activity of the body to prevent the accelerated development of diabetic complications.

Metabolic Syndrome as a Factor of Impairment of Antioxidant Defense System in Youth with T1DM.

Research indicates that adolescents with type 1 diabetes mellitus (T1DM) may develop both metabolic syndrome (MetS) and oxidative stress. The purpose of this study was to test the hypothesis that MetS could potentially affect antioxidant defense parameters. The study recruited adolescents aged 10-17 who had been diagnosed with T1DM, and divided them into two groups: "MetS+" (n = 22), who had been diagnosed with MetS, and "MetS-" (n = 81), who did not have metabolic syndrome. A control group consisting of 60 healthy peers without T1DM was included for comparison. The study examined cardiovascular parameters, such as complete lipid profile and estimated glucose disposal rate (eGDR), as well as markers of antioxidant defense. The results revealed a statistically significant difference between the MetS+ and the MetS- group in terms of total antioxidant status (TAS) (1.186 mmol/L vs. 1.330 mmol/L), and oxidative stress index (OSI) levels (0.666 vs. 0.533). Furthermore, multivariate correspondence analysis identified individuals with HbA1c < 8%; eGDR > 8 mg/kg/min, using either flash or continuous glucose monitoring systems, as MetS- patients. The study also found that eGDR (AUC 0.85, p < 0.001), OSI and HbA1c (AUC 0.71, p < 0.001) markers may be useful for diagnosing the onset of MetS in adolescents with T1DM.

Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes.

Introduction: The prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual ß-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation. Methods: We assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and ß-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients' levels of selected inflammatory cytokines at baseline. Results: Subjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group. Discussion: Higher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual ß-cell function. The process seems to be mediated by inflammatory cytokines.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

Elastographic Evaluation of Thyroid Nodules in Children and Adolescents with Hashimoto's Thyroiditis and Nodular Goiter with Reference to Cytological and/or Histopathological Diagnosis.

There are data indicating the coexistence of papillary thyroid carcinoma and autoimmune thyroiditis (AIT) in children. The aim of the study was elastographic evaluation of thyroid nodules in children and adolescents with AIT and nodular goiter in relation to cytological and/or histopathological diagnosis. We examined 215 children (57 boys and 158 girls) with 261 thyroid nodules (143 non-AIT and 118 AIT). All study participants underwent a conventional ultrasound examination with elastography followed by fine needle aspiration biopsy (FNAB). Abnormal Strain Ratio (SR ≥ 5) was observed in 36 non-AIT nodules and 15 AIT nodules. Papillary thyroid carcinoma was diagnosed in 5 patients (2% of all investigated nodules). SR of malignant thyroid nodules was statistically higher in comparison to SR of benign nodules both in the group of non-AIT (6 ± 4 vs. 3.67 ± 2.62, p = 0.024) and AIT nodules (6.3 ± 0.01 vs. 2.92 ± 1.89, p = 0.047). Comparison of non-AIT and AIT benign nodules revealed that SR was higher in non-AIT nodules (3.67 ± 2.62 vs. 2.92 ± 1.89, p = 0.01). We observed a strong positive correlation (R = 1) between TSH concentration and SR ratio in the group of all malignant thyroid nodules. Autoimmune inflammatory process of the thyroid gland does not limit the use of elastography in the diagnosis of thyroid nodules in children.

Atypical diabetes mellitus in children - when to suspect drug-induced diabetes. A case-based review of the literature.

INTRODUCTION: Drug-induced diabetes mellitus (DIDM) could be defined as a heterogenic group of diabetes caused by pharmacotherapy. The DIDM is considered to be reversible after discontinuation of diabetogenic treatment, but there is a risk of persistence, which is related to the duration of treatment, prescribed medication, and body mass index. CASE PRESENTATION: A 13-year-old boy treated for nephrotic syndrome with the use of tacrolimus and prednisone was diagnosed with diabetes during a check-up visit. On admission, he showed a cushingoid appearance and complained of dry mouth, which was not accompanied by polyuria or polydipsia. Blood tests showed elevated levels of glucose, and glycated A1c fraction of haemoglobin (HbA1c = 10.2%). Pancreatic islet autoantibodies were negative. The fasting and postprandial C-peptide levels were within the normal range. Diabetic ketoacidosis was excluded. Intensive insulin therapy was initially introduced; the daily dose of insulin per kilogram was low (TDD/kg = 0.31 U/kg). Those findings prompted us to consider diabetes mellitus type 2 or DIDM. Moreover, the TDD/kg and HbA1c additionally decreased after the steroid withdrawal. Because he was constantly on diabetogenic therapy and experienced periodical hyperglycaemia, DIDM could not be excluded. Therefore, our patient remained on insulin treatment. CONCLUSIONS: DIDM in children is challenging for all specialists. Diabetologists need to remember about this rare subtype of diabetes, and other specialist should perform screening on their patients who are at risk of DIDM. There is a great need for guidelines that would provide a standardized approach for diagnosing and treating DIDM in the paediatric population.

Immunological balance between Treg and Th17 lymphocytes as a key element of type 1 diabetes progression in children.

Type 1 diabetes (T1D) is autoimmune destruction of the beta cells of pancreatic islets. Due to complexity of that disease, the mechanisms leading to the tolerance breakdown are still not fully understood. Previous hypothesis of imbalance in the Th1 and Th2 cells as the main contributing factor has been recently changed towards role of other lymphocytes - regulatory (Treg) and IL-17A-producing (Th17). Our study aims to assess changes within Treg and Th17 cells in newly diagnosed T1D pediatric patients and their association with disease remission. Flow cytometry implementation allowed for Treg and Th17 analysis in studied groups and further combination with clinical and laboratory data. In addition, expression of diabetes-related genes was tested and evaluated in context of their association with studied lymphocytes. Initial results revealed that Treg and ratio Treg/Th17 are significantly higher in T1D than in healthy controls. Moreover, patients with lower HbA1c and daily insulin requirements demonstrated higher levels of Tregs. Similar tendency for insulin intake was also observed in reference to Th17 cells, together with high levels of these cells in patients demonstrating higher values for c-peptide after 2 years. In low-level Treg patients, that subset correlates with the c-peptide in the admission stage. In addition, higher levels of IL-10 were associated with its correlation with HbA1c and insulin dosage. In the context of gene expression, moderate associations were demonstrated in T1D subjects inter alia between CTLA4 and Treg or ratio Treg/Th17. Cumulatively, our data indicate a possible novel role of Treg and Th17 in mechanism of type 1 diabetes. Moreover, potential prognostic value of these populations has been shown in reference to diabetes remission.

The Relationship between Selected Inflammation and Oxidative Stress Biomarkers and Carotid Intima-Media Thickness (IMT) Value in Youth with Type 1 Diabetes Co-Existing with Early Microvascular Complications.

Recent years have confirmed the importance of oxidative stress and biomarkers of inflammation in estimating the risk of cardiovascular disease (CVD) and explaining not fully understood pathogenesis of diabetic macroangiopathy. We aimed to analyze the relation between the intima-media thickness (IMT) of common carotid arteries and the occurrence of classical cardiovascular risk factors, together with the newly proposed biomarkers of CVD risk (high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), adiponectin, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and vitamin D) in youth with type 1 diabetes (T1D) recognized in screening tests to present early stages of microvascular complications (VC). The study group consisted of 50 adolescents and young adults with T1D, mean age 17.1 years (10-26 age range), including 20 patients with VC (+) and 30 VC (-). The control group (Control) consisted of 22 healthy volunteers, mean age 16.5 years (11-26 age range). In the VC (+) patients, we found a significantly higher concentration of HbA1c, lipid levels, hsCRP and NT-proBNP. BMI and blood pressure values were highest in the VC (+) group. Higher levels of MPO and lower levels of vitamin D were found in both diabetic groups vs. Control. IMT in VC (+) patients was significantly higher and correlated positively with HbA1c, hsCRP, NT-pro-BNP and negatively with vitamin D levels. In conclusion, youth with T1D and VC (+) present many abnormalities in the classical and new CVD biomarkers. hsCRP and MPO seem to be the most important markers for estimating the risk of macroangiopathy. NT-proBNP may present a possible marker of early myocardial injury in this population.

Multi-Faceted Influence of Obesity on Type 1 Diabetes in Children - From Disease Pathogenesis to Complications.

The prevalence of overweight and obesity among youth patients with diabetes type 1 is increasing. It is estimated, that even up to 35% of young patients with this type of diabetes, considered so far to be characteristic for slim figure, are overweight or even obese. General increase of obesity in children's population complicates differential diagnosis of the type of diabetes in youths. Coexistence of obesity has clinical implications for all stages of diabetes course. It is confirmed that obesity is the risk factor for autoimmune diabetes, and is connected with the earlier onset of diabetes in predisposed patients. Many diabetic patients with obesity present additional risk factors for macroangiopathy, and are recognised to present metabolic syndrome, insulin resistance, and typical for diabetes type 2 - polycystic ovary syndrome, or non-alcoholic fatty liver disease. The prevalence of obesity rises dramatically in adolescence of diabetic child, more often in girls. It has negative impact on metabolic control, glycaemic variability and insulin demand. The risk for microangiopathic complications increases as well. The treatment is difficult and includes not only insulinotherapy and non-pharmacological trials. Recently treatment of insulin resistance with biguanids, and treatment with typical for type 2 new diabetes drugs like GLP-1 analogues, SGLT-2 receptor inhibitors, or even cases of bariatric surgery also has been reported.

Prevalence of Metabolic Syndrome in Relation to Cardiovascular Biomarkers and Dietary Factors among Adolescents with Type 1 Diabetes Mellitus.

The occurrence of metabolic syndrome (MetS) significantly affects the course of diabetes mellitus (DM), resulting in deterioration of insulin sensitivity and metabolic control, as well as many cardiometabolic complications. The aim of the study was to investigate the relationships between cardiovascular biomarkers, nutritional status, dietary factors and the occurrence of MetS among 120 participants from northeast Poland (adolescents with type 1 DM and healthy peers). MetS was assessed using several criteria: nutritional status by anthropometric measurements, body composition analysis by bioelectrical impedance, and diet using a food diary and questionnaire. MetS was diagnosed in every third diabetic. Compared to healthy peers, MetS patients had higher total body fat (26% vs. 14%, p < 0.001) and visceral fat (77 cm2 vs. 35 cm2, p < 0.001), and lower total antioxidant status (1.249 mmol/L vs. 1.579 mmol/L, p < 0.001). Additionally, their diet was rich in saturated fatty acids, but low in dietary fiber as well as mono- and polyunsaturated fatty acids. The group of diabetics reported many inappropriate eating behaviors. The combination of those with the presence of an excessive content of visceral fat tissue and abnormal values of MetS components may negatively affect metabolic control, thus accelerating the development of cardiometabolic complications.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.