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IIntroduction Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the -521C>T DRD4 gene polymorphism may correlate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. Methods The connection of the -521C>T DRD4 gene polymorphism with the DM1 and its comorbidities as well as the levels of serum pro- and anti-inflammatory markers, lipid profiles and values of monocyte subsets was evaluated. Results The key results of our study are as follows: 1) CC genotype and C allele are associated with a reduced risk of DM1 development (OR = 0.593, p = 0.005 and OR = 0.725, p = 0.003; resp.) whereas TT genotype and T allele are associated with a higher risk of DM1 (OR = 1.408, p = 0.04 and OR = 1.380, p = 0.003; resp.); 2) CC genotype is associated with an increased risk of dyslipidemia and retinopathy in diabetic patients (OR = 2.376, p = 0.001 and OR = 2.111, p = 0.01; resp.); 3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16+ monocytes (p = 2*10-4 and 0.04 resp.); 4) the DRD4 -521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. Discussion/Conclusion Our data imply that the dopaminergic signaling pathways may play an important role in the etiology of DM1 as well as its comorbidities and will provide a new insight into the DM1 risk management. The -521C>T DRD4 gene polymorphism could be considered a genetic marker to predict susceptibility to DM1 as well as retinopathy and dyslipidemia progress in patients with already established disease.

The paper’s main research aim is to verify the assumption that the way the Spanish Constitution was amended in 2011 means a rupture with the over 40-year-old political principle of including all parties represented in the Cortes Generales in this process. It is also indicated what disruptions it might cause in the operation of the Spanish political system. The source material selected for analysis consists of Spanish official journals and press from 2011. The applied research methods are the legal-institutional analysis and the comparative approach.

Using data from a large-scale screening program (N = 19634), we aimed to prospectively identify factors predicting uptake (i.e. acceptance of the invitation) and engagement (i.e. participation in at least two sessions) in a multi-component-intensive-behavioral-intervention for obesity-management (MBIOM) intervention targeting adolescents (n = 2862; 12-14 years; BMI ≥90th percentile). Approximately one third of adolescents most in need of weight management declined the initial invitation to enter the MBIOM. Poor diet, sedentary behavior, and parental education predicted willingness to enter and stay in the intervention, however measured body mass index did not matter. Perceived family support, instead of initial motivation, facilitated engagement. Our results provide new insights on the importance of regional socio-geographical factors including trust in local authorities.

Therapy for type 1 diabetes (T1DM) focuses on maintaining optimal blood glucose levels, achieved with intensive insulin treatment, proper nutrition, and physical activity. The aim of this study was to investigate postprandial glycemic changes under low (30%) and standard (50%) carbohydrate diets in adolescents with T1DM. A single-center cross-over nutritional study was conducted, during which 26 adolescent patients provided 220 continuous glucose-monitored (CGM) meals data from the two consecutive 3-day nutritional plans. Overall, the 50% carbohydrate diet was associated with higher postprandial glucose variability in the small meals (afternoon snacks, second breakfast) and greater postprandial peaks for other meals (breakfast, dinner, supper). Nevertheless, after the adjustment of a patient’s individual clinical variables (age, Tanner classification, glucose disposal rate), we observed that mean postprandial glucose was higher for afternoon snacks and lower for suppers in the 30% carbohydrate diet. Although a 30% carbohydrate diet seems to offer better postprandial glycemia, it requires additional attention from the physician and patient when it comes to modifying daily carbohydrate intake. Increased fat/protein content and size of the main meal lead to a prolonged postprandial glycemic response, which may affect the insulin treatment and result in suboptimal glycemic control.

Introduction Transcutaneous oxygen pressure (tcPO2) is a non-invasive method of measuring skin oxygenation that may reflect its superficial perfusion. Skin microvasculature may be impaired in patients with late onset of type 1 diabetes (DM1). However, its condition in children has not been fully determined. Aim To compare tcPO2 in children with short-lasting non-complicated DM1 and age-matched healthy controls with regard to concomitant vascular risk factors. Material and methods The study group consisted of 51 paediatric patients aged 14.9 (8.4-18.0) years with short-lasting DM1 without clinical evidence of diabetic micro- or macroangiopathy and 28 control subjects aged 14.8 (11.3-17.7) years. TcPO2 was tested prior, during and after applying post-occlusive reactive hyperaemia (PORH) test in standardized conditions. Biochemical parameters were assessed and then compared between the groups. Results TcPO2 at maximal ischemia during PORH was higher in the DM1 patients than in healthy controls (2.4 (0.7-18.8) vs. 1.6 (0.4-12.0), p = 0.002). No differences were found regarding the tcPO2 measurements recorded prior to ischemia or after recovery. In DM1, concentrations of total cholesterol, triglycerides, HbA1c and TSH were significantly higher than in healthy controls. The fT4 levels were significantly lower in the DM1 group. After adjusting for lipid levels, no differences in tcPO2 were found, and a multivariate analysis showed the cholesterol levels have a significant impact on tcPO2 response to maximal ischemia. Conclusions Our results indicate that increased lipid levels are responsible for the impaired skin response to ischemic stimuli in short-lasting DM1. This supports the importance of aggressive lipid control in prevention of early onset microangiopathy in those patients.

Abstract Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. Key messages We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

Monotherapy with autologous expanded CD4We conducted a three-arms clinical trial to explore the efficacy and safety of the combined treatment with Tregs and rituximab in paediatric patients with T1DM. The patients were allocated to three groups: Tregs only (n = 13), Tregs + rituximab (n = 12) and control (n = 11). The key primary efficacy analyses were C-peptide levels (mixed meal tolerance test) and the proportion of patients in remission at 12 and 24 months.At month 24, as compared with the control, both treatment groups remained superior in the area under the curve of C-peptide mixed meal tolerance test, whereas in the analysis of all visits only the combined therapy improved area under the curve at 12 and 24 months. The proportion of patients in remission was significantly higher in the combined group than in the control group at 3, 6, 9 and 21 months but not at 18 and 24 months. There was no significant difference between the Tregs only group and control group. Adverse events occurred in 80% patients, mostly in the combined group and Tregs only group. No adverse events led to the withdrawal of the intervention or death. All comparisons were performed with alpha level of 5%.Over 2 years, combined therapy with Tregs and rituximab was consistently superior to monotherapy in delaying T1DM progression in terms of C-peptide levels and the maintenance of remission.

Abstract As the KL-VS haplotype alters secretion and activity of KLOTHO and uric acid (UA) is associated with endothelial dysfunction and inflammation, their mutual links may contribute to microalbuminuria (MA) in patients with type 1 diabetes (T1D). Therefore, we hypothesize that KL-VS polymorphism could be associated with the prevalence of MA in T1D patients, and KL-VS polymorphism could modify physiological functions and pathogenic potential of UA. We have examined 350 patients with T1D. The analysis concerned KL-VS polymorphism along with the concentrations of serum inflammatory markers, indicators of renal function, blood pressure, and lipid profile. The incidence of KL-VS genotype was lower in a group with MA in comparison to patients without this condition. Moreover, KL-VS carriers had improved indicators of renal function, lower concentrations of pro-inflammatory cytokines, and higher levels of anti-inflammatory markers. Simultaneously, among KL-VS carriers serum UA was negatively correlated with HbA1c, albumin excretion rate, ACR, CRP, TNF-α, total cholesterol, LDL-C and triglycerides, and positively correlated with HDL-C. Moreover, among wild-type KLOTHO carriers serum, UA was in positive correlation with creatinine, blood pressure, IL-12 and MCP-1, and in negative correlation with IL-10 and eGFR. Findings of our study suggest that the functional KL-VS polymorphism is independently associated with MA and the KL-VS genotype protects from the development of MA, and KL-VS polymorphism may modify physiological functions and pathogenic potential of UA by altering the levels of HbA1c, inflammatory biomarkers, indicators of renal function, blood pressure, and lipid profile. Key messages • We analyzed the KL-VS polymorphism and the UA serum level in patients with T1D. • The KL-VS polymorphism is independently associated with microalbuminuria. • The KL-VS alleles protect from the development of microalbuminuria. • KL-VS polymorphism may modify physiological functions and pathogenic potential of uric acid.

From year to year, we observe constantly growing revenue from the sale of supplements and functional food for athletes. The increased interest in their use raises many questions concerning the choice of products, portions, in addition in the case of athletes with type 1 diabetes - how they affect the level of glycaemia. In the group of people under 18 with diagnosed type 1 diabetes, the properly selected supplementation, which will not cause undesirable effects, is even more important. This publication aims to summarize the current reports on nutrients that come from: the present scientific knowledge, information on the labels, and information available on the websites of the most popular companies producing nutrients on the Polish market.Z roku na rok obserwuje się stale rosnące przychody ze sprzedaży suplementów i żywności funkcjonalnej dla sportowców. Rosnące zainteresowanie ich zastosowaniem rodzi wiele pytań dotyczących wyboru produktów, porcji, a także w przypadku sportowców z cukrzycą typu 1 – w jaki sposób wpływają one na poziom glikemii. W grupie osób poniżej 18. roku życia z rozpoznaną cukrzycą typu 1 odpowiednio dobrana suplementacja, która nie spowoduje niepożądanych skutków, jest jeszcze ważniejsza. Niniejsza publikacja ma na celu podsumowanie bieżących raportów na temat odżywek, które pochodzą z: aktualnej wiedzy naukowej, informacji na etykietach oraz informacji dostępnych na stronach internetowych najpopularniejszych firm produkujących odżywki na polskim rynku.

Childhood obesity is a complex problem that requires a multidimensional approach. The constantly increasing prevalence of childhood obesity should be of interest not only to pediatricians but also government bodies. Parental awareness of how excess body weight influences a child's health is one of the aspects that should be considered.Our main goal was to assess the awareness and opinions on possible adverse effects of excess body weight of parents of children attending several primary schools in the Pomeranian, Lubelskie and Świętokrzyskie Voivodships in Poland.The questionnaire-based survey was conducted in 2019 during parent-teacher meetings in public schools in the Pomeranian, Lubelskie and Świętokrzyskie Voivodeships Statistical analysis was then performed on the 277 received questionnaires using Statistica 13.3 software package and spreadsheet editor Microsoft Excel 2018.Inhabitants of urban areas perceived a stronger link between obesity and its influence on health. Similar results were observed in the group consisting of parents with higher education. Gender had no significant effect on the opinion concerning complications of obesity.Overall, most of the parents recognized the influence of obesity on health. The degree of awareness among respondents was the weakest in relation to the influence of obesity and diet on carcinogenesis.Otyłość u dzieci jest złożonym problemem, który wymaga wielowymiarowego podejścia. Stale rosnąca częstość występowania otyłości wśród dzieci powinna zainteresować nie tylko pediatrów, lecz także organy rządowe. Świadomość rodziców, w jaki sposób nadmierna masa ciała wpływa na zdrowie dziecka, jest jednym z aspektów, które należy wziąć pod uwagę.Naszym głównym celem była ocena świadomości i opinii na temat możliwych negatywnych skutków nadmiernej masy ciała rodziców dzieci uczęszczających do kilku szkół podstawowych w województwach pomorskim, lubelskim i świętokrzyskim w Polsce.Badanie ankietowe przeprowadzono w 2019 r. podczas zebrań z rodzicami w szkołach publicznych w województwach pomorskim, lubelskim i świętokrzyskim. Następnie przeprowadzono analizę statystyczną 277 otrzymanych kwestionariuszy przy użyciu pakietu oprogramowania Statistica 13.3 i edytora arkuszy kalkulacyjnych Microsoft Excel 2018.Mieszkańcy obszarów miejskich dostrzegli silniejszy związek między otyłością i jej wpływem na zdrowie. Podobne wyniki zaobserwowano w grupie rodziców z wyższym wykształceniem. Płeć nie miała istotnego wpływu na opinię dotyczącą powikłań otyłości.Większość rodziców dostrzegła wpływ otyłości na zdrowie. Poziom świadomości wśród respondentów był najsłabszy w odniesieniu do wpływu otyłości i diety na kancerogenezę.

Overweight and obesity rates in children and adolescents increase worldwide for over 30 years, what leads to an increased risk of de-veloping metabolic diseases.Protocol description and preliminary results of the largest to-date obesity management programme for children in Poland - "PoZdro!"The Programme is based on three main steps: screening, parental engagement and long-term behavioral intervention (medical, dietetic, psychological, physical activity intervention panels) and education activities in secondary schools. Over 30.000 children were screened in four big Polish cities and over 2.000 engaged in the programme.Preliminary results from the first city show that, since 2014, 3998 of the 6346 (63%) eligible students from 24 schools (first grade of the secondary school) were screened. 16% of the children were overweight (body mass index - BMI ≥ 85th95th centile) and 4.7% were obese (BMI ≥95th centile). 603 children fulfilling the qualification (QUA) criteria (BMI90th centile) were offered the Individual Integrated Care (IIC). 470 (77.94% of QUA) began and 253 (41.96% of QUA, 53.82% of IIC) finished the full interventional pro-gramme with the mean BMI centile decrease of 3.04 in two following years."PoZdro!" is a unique obesity prevention and management programme in Poland operating simultaneously in several Polish big cities. The programme incorporates parental engagement and long-term behavioral intervention. Preliminary results show that it may result in meaningful decrease in BMI in two following years. Further data analyses are necessary to show the influence of the programme on metabolic risk in studied group.Od ponad 30 lat obserwuje się rosnący trend otyłości wśród dzieci i młodzieży na całym świecie, co skutkuje zwiększeniem ryzyka rozwoju chorób metabolicznych.Opis protokołu oraz wstępne wyniki dotychczas największego programu profilaktyki oraz walki z otyłością u dzieci w Polsce „Po-Zdro!”.Program oparty jest na trzech filarach: skriningu, zaangażowaniu opiekunów podczas długotrwałej interwencji behawioralnej (panele lekarza, dietetyka, psychologa, specjalisty aktywności fizycznej) oraz zajęciach edukacyjnych w szkołach średnich. Program zapewnia skoordynowaną pomoc dla nastolatków z nadwagą lub otyłością oraz ich rodzin w 4 dużych polskich miastach. W skriningu uczestni-czyło ponad 30 000, a w Programie ponad 2000 dzieci.Wstępne wyniki z Gdyni pokazują, iż od 2014 r. przebadano 3998 spośród 6346 (63%) kwalifikujących się uczniów z 24 szkół (pierw-sza klasa szkoły średniej). U 16% dzieci stwierdzono nadwagę (wskaźnik masy ciała; body mass index – BMI ≥ 85. centyla95. cen-tyla) a u 4.7% otyłość (BMI ≥ 95. centyla). Dzieciom spełniającym kryteria włączenia do programu (603 dzieci z BMI90. centyla) zaproponowano udział w zintegrowanej opiece indywidualnej (ZOI). Z tego 470 (77,94% z zakwalifikowanych) rozpoczęło, a 253 (41,96% zakwalifikowanych, 53,82% z ZOI) ukończyło program interwencyjny ze średnim obniżeniem centyla BMI o 3,04 po 2 latach.„PoZdro!” jest jedynym programem zapobiegania oraz walki z otyłością w Polsce przeprowadzanym jednocześnie w kilku dużych mia-stach. Program łączy zaangażowanie opiekunów z długotrwałą interwencją behawioralną. Wyniki wstępne pokazują, że skoordynowana, wielodyscyplinarna interwencja może przyczynić się do znacznego zmniejszenia BMI na przestrzeni 2 lat. Dalsze analizy danych po-zwolą na ocenę wpływu programu na ryzyko rozwoju chorób metabolicznych w badanej grupie.

Children with severe central nervous system (CNS) impairment are at risk of developing various degrees of nutritional deficit that require long-term nutritional intervention. Interventions are most often implemented through enteral nutrition (EN) using commercially manufactured feeds administered via gastro/jejunostomy or nasogastric or nasojejunal tubes. The modality of feeding—continuous feeding or bolus feeding—is dependent on the function of the gastrointestinal tract, particularly the efficiency of gastric emptying. In the literature, the relationship between this type of nutrition and the occurrence of hyperglycaemia is often discussed. In addition, children with chronic neurological diseases are vulnerable to disorders of many mechanisms of neurohormonal counter-regulation related to carbohydrate management, and due to limited verbal and logical contact, it is difficult to recognise the symptoms of hypoglycaemia in such patients. We aimed to assess the carbohydrate metabolism in children with severe CNS impairment, with enteral nutrition delivered via nasogastric, nasoenteral, or percutaneous tubes, based on continuous glycaemic monitoring (CGM) and the measurement of glycated haemoglobin (HbA1c) levels. Materials and methods: This prospective, observational study included nineteen patients (median (25–75 pc) age: 12.75 (6.17–15.55) years) with permanent CNS damage (Gross Motor Function Classification System V) receiving long-term tube enteral feeding, recruited from two paediatric university nutritional treatment centres. Patients with acute conditions and diagnosed diabetes were excluded. The nutritional status and nutritional support were analysed in all the inpatients in accordance with a uniform protocol. Using the CGM system (Medtronic iPro2), glycaemic curves were analysed, and in addition, HbA1C levels were determined in fourteen patients. CGM results were analysed using GlyCulator2.0. Statistical analysis was performed using the Statistica version 11 software (StatSoft Inc. Tulsa, OK, USA). Results: More than half (11/19; 58%) of the patients were undernourished (BMI < 3 pc for age and gender), with the stature age being significantly lower than calendar age (5 (4.5–9) vs. 12.75 (6.17–15.55) years; p = 0.0010). The actual caloric intake was 50 (37.7–68.8) kcal/kg (median; 25–75 pc). In patients fed using the bolus method, the number of calories consumed per day was statistically significantly higher than in children subjected to a continuous feeding supply (56.00 (41.00–75.00) vs. 33.40 (26.70–50.00) kcal/kg BW (body weight; p = 0.0159). Decreases in blood glucose levels below the alarm level ( 140 mg/dL (TAR 140) recorded overnight in children with BMI ≥ 3 amounted to 1.6% vs. 0% in undernourished patients (TAR 140: 0.0 (0.00–1.6%) vs. 0% (0.00–0.0%; p = 0.0375); the percentage of glycaemic concentrations

Monogenic diabetes caused by mutation in the glucokinase gene (GCK-MD) is a rare disorder manifesting in childhood as mild, prevalent hyperglycemia. By consensus, it is managed by dietary supervision and infrequent consultations. However, its impact on the mental health of the affected children is largely unknown.To estimate the prevalence of psychiatric comorbidities in children with monogenic glucokinase-related diabetes (GCK-MD) and evaluate their association with quality of life (QoL).The study invited children with GCK-MD aged 5-18 years identified in the Central National Registry and treated in 3 pediatric diabetes centers in Poland. The control group comprised children with type 1 diabetes (T1D, the most common diabetes type in youth) matched for age and family history of diabetes. Participants underwent a semistructured clinical interview diagnostic for psychiatric comorbidities, questionnaires assessing behavioral problems, depressive symptoms, parental stress, and measuring general and diabetes-related QoL (PedsQl).We included 35 patients with GCK-MDMD and 199 with T1D. Eight (22.9%) GCK-MD patients were diagnosed with psychiatric disorder in their lifetime, compared with 16 (8.1%) in the T1D group (odds ratio 3.4 [95% confidence interval: 1.3-8.7]). Patients with GCK-MD showed better parent-reported general QoL (87.1 ± 11.9 vs 82.0 ± 14.0, P = 0.0060) and higher diabetes-related QoL in both parental (84.5 ± 13.8 vs 74.1 ± 15.2, P0.0001) and child's perspective (87.6 ± 10.9 vs 77.3 ± 13.9, P0.0001). Psychiatric disorders (+P) were associated with worse child-reported diabetes QoL (T1D+P 66.6 ± 16.7, T1D-P 78.2 ± 13.3, GCK-MD+P 79.6 ± 16.3, GCK-MD-P 90.1 ± 7.5, P = 0.0002).High prevalence of psychiatric disorders in children with GCK-MD and lower QoL emphasizes the need for psychologic surveillance in those otherwise mildly-treated patients.

Aim: The aim of the study was to investigate the relationship between the concentration of psychrophilic bacteria, mesophilic bacteria and mold fungi in bioaerosols, and the number of new cases of type 1 diabetes mellitus (T1DM) in children. Methods: Air samples from the Lubelskie and Pomeranian voivodeships in Poland were collected from January 2015 to December 2016 in winter, spring, summer and autumn. Thirty-three samples were collected in the Pomeranian and 27 in the Lubelskie voivodeship. The air samples were collected on the first day of each month at 1:00 pm for 10 mins at a height of 1.5 m above the ground. The number of mesophilic bacteria was detected after 24–48 hrs incubation at 37°C on tryptone soya agar (TSA; Merck, Darmstadt, Germany). The number of psychrophilic bacteria was detected after 72 hrs incubation at 22°C on TSA. The number of fungi was detected by a 5-day long incubation at 28°C on chloramphenicol yeast glucose agar. Results: In the Lubelskie voivodeship, the mean concentration of psychrophilic bacteria was significantly higher than in the Pomeranian voivodeship (2739 vs 608 CFU/m3, respectively), the mean concentration of mesophilic bacteria was significantly higher (2493 vs 778/m3, respectively) and the concentration of fungi was significantly higher (3840 vs 688 CFU/m3, respectively). We also showed a statistically significant relationship between the number of children with recently diagnosed T1DM and the mean concentration of psychrophilic and mesophilic bacteria in the Pomeranian and Lubelskie voivodeships (P

Background The impairment of endothelial function in type 1 diabetes mellitus (DM1) is considered as the basis of microvascular complications. In DM1 patients autoimmune thyroiditis is a frequent comorbidity which may be responsible for further deterioration of microcirculation function. In studies investigating the relationship between cardiovascular risk factors and microvascular function, skin microcirculation is widely used. The aim of our study was to evaluate the impact of coexisting autoimmune thyroiditis on skin microcirculation in children with type I diabetes mellitus. Subjects The study group consisted of 25 pediatric DM1 patients, 25 pediatric patients with type 1 diabetes and autoimmune thyroiditis (DM1 + AIT) and 29 control subjects matched for age and gender. The DM1 and DM1 + AIT patients were also matched for age at onset of DM and diabetes duration. Methods Performed capillaroscopy studies employed non-selective stimuli such as post-occlusive reactive hyperemia (PORH) and venous occlusion (VO) tests. The relative area covered by capillaries (coverage) and the distance between capillaries were assessed. These measurements were performed before tests as well as after PORH and VO. Results Coverage at baseline, after PORH and VO and distance after VO differ significantly between control subjects and the group DM1 + AIT. The coverage at baseline, after PORH and VO were significantly smaller in DM1 + AIT compared with the control group. Post-hoc analysis after controlling for lipids levels showed that differences between the DM1 + AIT and control group were remained only for coverage at baseline and after VO. Significant differences between DM1 + AIT and DM1 and control group for coverage after VO were also presented. Conclusions Coexisting autoimmune thyroiditis significantly deteriorates skin microcirculation function in pediatric non-complicated type 1 diabetic patients. This process is independent of patient age, diabetes duration and age of diabetes onset.

Alternatively activated macrophages (M2) exert anti-inflammatory effects and are crucial for keeping balance between protective and destructive cell-mediated immunity in healing phase of inflammation. Two members of the interferon regulatory factors family, IRF5 and IRF4, are known to promote M1 or M2 phenotype, respectively. Our study aimed to analyse the effectiveness of the M2 differentiation process in vitro (achieved by IL-4 stimulation) and its relationship to the stage of type 1 diabetes mellitus (DM1) in juvenile patients. To identify the basic changes in M2 phenotype, we examined the expression of the surface CD206, CD14, CD86 molecules, intracellular IRF4 and IRF5 transcription factors as well as IL-10 and TNFα intracellular production. Ten newly diagnosed (ND-DM1) and ten long-standing (LS-DM1) patients were enrolled into the study. The control group consisted of six children. We observed a significantly higher number of unpolarised CD206+CD14+ cells in the M2 cultures of DM1 subjects when compared to healthy ones. Examined cells presented common features with M1 macrophages (high levels of the CD14/CD86/IRF5 markers); however, they were weak TNFα producers in ND-DM1 patients. For the first time, we have revealed dysregulated IRF4/IRF5 axis in the analysed subpopulation derived from diabetic patients. Additionally, monocytes of ND-DM1 children were still able to differentiate into regulatory IL-10+ M2 macrophages, while this process was highly limited in LS-DM1 patients. Summarising, we suggest that the M2 polarisation process is less effective in DM1 patients than in healthy subjects and it may vary depending on the stage of disease. It can be concluded that in vitro differentiated M2 macrophages may be used in the future as inflammatory inhibitors for adoptive therapy experiments in ND-DM1 subjects.

The CD83 molecule is a known marker of dendritic cell differentiation process, and its soluble form (sCD83) exerts immunosuppressive functions. In our research, we examined whether the sCD83 plasma concentration is impaired in DM1 children and if the expected changes are in line with the disturbed process of monocyte’s transformation into mCD83+ monocyte-derived cells. 28 newly diagnosed (ND-DM1) and 30 long-standing (LS-DM1) patients were enrolled into our study. We revealed that the examined cells show a high mCD83 expression level in ND-DM1, which was significantly downregulated by the TNF-α stimulation. The results were in line with those from healthy controls. We also observed that monocyte differentiation process into CD83+ cells was much defective in LS-DM1 children and the mCD83 expression level seems not to be controlled by TNF-α. Moreover, the sCD83 level was significantly decreased in plasma from LS-DM1 children and it was negatively related to HbA1c levels, while no correlations were observed between TNF-α plasma concentration or disease duration. Summarizing, our results suggest that reduced sCD83 levels may correspond with a poor metabolic control in LS-DM1 patients and therapeutic administration of this molecule may indicate a new therapy approach in the chronic phase of diabetes.

In the currently available literature there are no works investigating the correlation between CCR5-Δ32 polymorphism and dyslipidemia in children with type 1 diabetes mellitus (T1D). Therefore, we have decided to explore the potential role played by this polymorphic locus in the incidence of dyslipidemia as an important risk factor for cardiovascular disease (CVD) in patients with T1D.A total of 380 patients with T1D were selected. Patients were divided into two groups: 180 patients with diabetic dyslipidemia and 200 controls without dyslipidemia. Characterization of CCR5-Δ32 genotypes was analyzed by polymerase chain reaction. Logistic regression model was used to examine the association between CCR5-Δ32 polymorphism and dyslipidemia.When participants were analyzed according to CCR5-Δ32 polymorphism, Δ32 carriers presented higher levels of: HbA1c (p 0.001), fasting plasma glucose (p 0.001), LDL (p = 0.02) as well as TG (p = 0.01) and lower levels of HDL (p = 0.01) than noncarriers. Moreover, the minor allele Δ32 was more frequent in dyslipidemic subjects than controls (p 0.001) and conferred an increased individual risk for dyslipidemia (OR = 2.327; 95% CI = 11.241-4.365; p = 0.009).The findings of our study suggest that the CCR5-Δ32 polymorphism is associated with elevated plasma lipid levels and the Δ32 allele increases the risk of dyslipidemia in patients with T1D. Identification of the functional variant underlying these associations may potentially lead to the development of a novel and adjunctive approach for the treatment of dyslipidemia and CVD.

Health care provision for patients with diabetes mel­litus is a considerable challenge to health policy due to the increasing number of its new cases, both in adults and in children. In Poland, hospital care for children with diabetes mellitus is centralized and most services are provided by university and provincial hospitals. In spite of the above the structure of the services provided varies widely from province to province, both in terms of the number of hospitalizations per 100,000 children, net migration rate, length of hospital the stay, and percentage of hospitalizations for acute complications. It is necessary to improve the societal and medi­cal awareness regarding the signs and symptoms of diabetes in order to reduce the number of acute complications, including those at the time of diagno­sis. Furthermore, it is crucial to make every effort to provide equal access to specialist diabetes care, thus to make it consistent with the standards. The high number and differences in the numbers, duration of hospitalizations of children with diabetes require further monitoring at a coordinated system of pediatric care.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by a destruction of pancreatic  cells, which leads to absolute insulin deficiency. Persistently high glycaemia causes vascular damage throughout the body. Microvascular complications com-prise the following: nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease (leading to strokes), and peripheral vascular disease. The pathogene-sis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products. Precise understanding of these mechanisms could help clinicians to identify diabetic complications earlier and subsequently implement indispensable therapy on time. It is vital to determine biomarkers of microvascular and macrovascular complications in children affected with T1DM. Advanced glycation end-products and their receptors, adhesive molecules, pro- and anti-inflammatory cytokines, enzymes such as N-acetyl-β-D-glucosaminidase, and growth factors are the subject of ongoing studies. Numerous biomarkers of diabetic microangiopathy are already known and may constitute therapeutic targets in the future. Unfortunately, despite substantial progress in the understanding of the processes by which microvascular and macrovascu-lar complications develop, much effort still needs to be devoted to the matter, and further investigations are required.Cukrzyca typu 1 jest przewlekłą chorobą charakteryzującą się dysfunkcją komórek  wysp trzustki, co prowadzi do całkowitego braku wydzielania insuliny. Trwale podwyższona glikemia powoduje uszkodzenie naczyń w całym organizmie. Do powikłań mikronaczynio-wych cukrzycy należą: retinopatia, nefropatia i neuropatia. Do powikłań makroangiopatycznych można zaliczyć chorobę niedokrwienną serca prowadzącą do zawału mięśnia sercowego, chorobę naczyń mózgowych mogącą skutkować udarem i chorobę naczyń obwodo-wych. Patogeneza powikłań naczyniowych jest wieloczynnikowa i prawdopodobnie jest wynikiem bezpośredniego działania uszkadza-jącego glukozy na śródbłonek naczyniowy, stresu oksydacyjnego, produkcji sorbitolu i końcowych produktów glikacji. Dokładne zro-zumienie tych mechanizmów mogłoby pomóc klinicystom we wcześniejszym rozpoznawaniu powikłań cukrzycowych i następnie we wprowadzeniu wymaganej terapii w odpowiednim czasie. Określenie markerów cukrzycowych powikłań mikro- i makronaczyniowych u dzieci chorych na cukrzycę typu 1 jest niezwykle istotne. Produkty końcowej glikacji i ich receptory, cytokiny pro- i antyzapalne, en-zymy, takie jak N-acetyl-β-D-glukozaminidaza oraz czynniki wzrostu, są obiektem nieustannych badań. Liczne markery mikroangiopatii cukrzycowej są już poznane i w przyszłości mogą stanowić potencjalny cel terapeutyczny. Niestety, mimo znacznego postępu w zrozu-mieniu procesów, które prowadzą do powstawania powikłań mikro- i makronaczyniowych cukrzycy, wciąż dalsze badania są konieczne.

Overweight and obesity in children is becoming an increasingly common problem due to the increased access to processed food, overly high energy density diet, and limitation of physical activity in children. Such trends in today's society lead to health consequences that can be observed in the early stages of carbohydrate metabolism disorders. Reduction of body weight and changes in eating habits can prevent the onset of type 2 diabetes. Recently, the benefits of consuming products containing resistant starch, which has the main advantage of influencing the metabolic pathway of glucose, have been increasingly underlined. To date, no recommendations have been made for the daily intake of resistant starch or its content in individual products available on the food market. However, in the medical literature, there are an increasing number of reported cases of the beneficial effect of consuming resistant starch as a factor that supports glycaemic control in children with carbohydrate disorders. Unfortunately, the above topic requires further research in this direction, especially in the developmental age population, which will allow the formulation of precise conclusions regarding its use in the prevention of overweight, obesity, carbohydrate metabolism disorders, and the development of diabetes.Nadwaga i otyłość u dzieci staje się coraz częstszym problemem ze względu na zwiększony dostęp do przetworzonej żywności, zbyt dużą gęstość energetyczną diety oraz ograniczoną aktywność fizyczną u dzieci. Takie trendy dzisiejszego społeczeństwa prowadzą do występowania konsekwencji zdrowotnych, które na samym początku można zaobserwować w zaburzeniach gospodarki węglowodanowej. Redukcja masy ciała oraz zmiana nawyków żywieniowych mogą zapobiec wystąpieniu cukrzycy typu 2. Ostatnio coraz częściej podkreśla się korzyści ze spożywania produktów zawierających skrobię oporną, której główną zaletą jest wpływ na szlak metaboliczny glukozy. Do dnia dzisiejszego nie stworzono zaleceń dotyczących dziennego spożycia skrobi opornej ani nie uwzględniono jej zawartości w poszczególnych produktach dostępnych na rynku spożywczym. Mimo to w literaturze pojawia się coraz więcej doniesień o korzystnym wpływie spożywania skrobi opornej jako czynnika, który wspomaga kontrolę glikemii u dzieci z zaburzeniami gospodarki węglowodanowej. Niestety, powyższa tematyka wymaga dalszych badań w tym kierunku, szczególnie w populacji wieku rozwojowego, które pozwolą na sformułowanie precyzyjnych wniosków dotyczących jej stosowania w profilaktyce nadwagi, otyłości, zaburzeń gospodarki węglowodanowej i rozwoju cukrzycy.

Purpose Genetically predisposed individuals may develop several autoimmune diseases—autoimmune polyendocrine syndromes (APS). APS types 2–4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. BACH2 polymorphisms are associated with autoimmune disorders, including Addison’s disease (AD), Graves’ disease (GD), and probably type 1 diabetes (T1D). Our study was aimed to investigate the BACH2 variant, rs3757247, in endocrine autoimmunity in the Polish population. Methods The analysis comprised 346 individuals with APS, 387 with T1D only, and 568 controls. Genotyping was performed using TaqMan chemistry. Results APS type 2 was found in 219 individuals, type 3 in 102, and type 4 in 25 subjects. Overall, AD was diagnosed in 244 subjects, Hashimoto’s thyroiditis—in 238, T1D—in 127, GD—in 58, vitiligo and chronic gastritis each in 40 patients, celiac disease—in 28, premature menopause in 18, and alopecia in 4 patients. Minor T allele at rs3757247 was found in 56.4% APS vs. 44.1% control alleles (OR 1.59; 95%CI: 1.30–1.95, p p p-values > 0.05). Conclusions These results provide evidence of the association between BACH2 polymorphism and polyglandular autoimmunity. Since carriers of rs3757247 display increased risk for additional autoimmune conditions, this variant could identify individuals prone to develop APS.