The Role of Forkhead Box O in Pathogenesis and Therapy of Diabetes Mellitus.

Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic ß-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease.

Adiponectin is unrelated to kidney function or injury markers in renal transplant recipients: A one-year follow-up study.

BACKGROUND: Adiponectin (ADPN) is a biologically active cytokine produced by adipose tissue. This protein exhibits anti-inflammatory, antioxidant, antifibrotic, and insulin-sensitizing properties. As ADPN is primarily eliminated by the kidneys, it is a potential biomarker of chronic kidney disease progression. This study aimed to analyze the fluctuations in ADPN levels after kidney transplantation during a one-year follow-up and to compare them to significant renal (eGFR, NGAL) and metabolic (insulin, glucose, lipids, HOMA-IR) markers. METHODS: Insulin, ADPN, NGAL, and basic biochemical parameters were evaluated in 51 healthy controls and 39 patients right before kidney transplantation and at five time points following transplantation (5-7 days, one month, three months, six months, and twelve months). RESULTS: Mean ADPN levels dropped significantly right after transplantation (from 35.449 to 30.920 µg/mL, p = 0.001) and decreased gradually over a year. From the third month after the transplantation, ADPN levels were comparable to healthy individuals. At the pre-transplant time point, ADPN correlated only with insulin (r = -0.60, p < 0.001) and HOMA-IR (r = -0.55, p < 0.001). At the timepoints after transplantation, ADPN correlated only with NGAL at three months (r = -0.70, p = 0.048). The correlation of ADPN with HOMA-IR found at pre-transplant was not significant at any post-transplant time point, but at one and three months after transplant, the correlations reached a borderline significance (p = 0.07 and p = 0.08, respectively). CONCLUSIONS: Successful kidney transplantation is followed by a gradual and significant ADPN decrease. In pre- and post-transplant patients, ADPN is unrelated to kidney function defined by GFR, but to glucose metabolism. Most of the analyzed metabolic and kidney parameters, apart from NGAL, stabilize within three months after transplantation.

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes.

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.

Connexins-Therapeutic Targets in Cancers.

Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels. They participate in intercellular communication or communication between the intracellular and extracellular environments. Connexins affect cell homeostasis, growth and differentiation by enabling the exchange of metabolites or by interfering with various signalling pathways. Alterations in the functionality and the expression of connexins have been linked to the occurrence of many diseases. Connexins have been already linked to cancers, cardiac and brain disorders, chronic lung and kidney conditions and wound healing processes. Connexins have been shown either to suppress cancer tumour growth or to increase tumorigenicity by promoting cancer cell growth, migration and invasiveness. A better understanding of the complexity of cancer biology related to connexins and intercellular communication could result in the design of novel therapeutic strategies. The modulation of connexin expression may be an effective therapeutic approach in some types of cancers. Therefore, one important challenge is the search for mechanisms and new drugs, selectively modulating the expression of various connexin isoforms. We performed a systematic literature search up to February 2020 in the electronic databases PubMed and EMBASE. Our search terms were as follows: connexins, hemichannels, cancer and cancer treatment. This review aims to provide information about the role of connexins and gap junctions in cancer, as well as to discuss possible therapeutic options that are currently being studied.

The Role of Endocan in Selected Kidney Diseases.

Endocan, previously referred to as an endothelial-cell-specific molecule-1 (ESM-1) is a member of a proteoglycan family that is secreted by vascular endothelial cells of different organs, mainly lungs and kidneys. It is assumed to participate in endothelial activation and the triggering of inflammatory reactions, especially in microvasculatures. Thanks to its solubility in human fluids, i.e., urine and blood plasma, its stability and its low concentrations in physiological conditions, endocan has been proposed as an easily available, non-invasive biomarker for identifying and predicting the course of many diseases. Recently, endocan has been studied in relation to kidney diseases. In general, endocan levels have been linked to worse clinical outcomes of renal dysfunction; however, results are conflicting and require further evaluation. In this review, authors summarize available knowledge regarding the role of endocan in pathogenesis and progression of selected kidney diseases.

Common carotid pulsatility is deteriorated by autoimmune thyroiditis in children with type 1 diabetes mellitus - A pilot study.

Autoimmune thyroiditis (AIT) frequently coexists with type 1 diabetes (DM1) and additionally increases the extent of microcirculatory complications due to DM1. We hypothesized that in pediatric patients with DM1, impairment of macrocirculation could be further augmented by a coexisting autoimmune process. Therefore, we investigated the influence of AIT on large arteries in DM1 pediatric patients. Our group consisted of 19 DM1, 19 DM1 + AIT patients and 29 control subjects. The groups were comparable regarding age and gender. The DM1 and DM1 + AIT patients were matched for age at onset of DM1 and diabetes duration. Macrocirculation was described using pulsatility indices (PIs) determined for common carotid (CCA) and peripheral arteries of upper and lower limbs. CCA resistance index (RI) and ABI were also assessed. Children with DM1 + AIT had only significantly lower CCA_PI and CCA_RI in comparison with controls whereas in the absence of AIT such difference was not found. The diabetes duration and age of onset did not correlate with carotid indices. Total cholesterol level was higher both in DM1 + AIT and DM1 groups than in the control group. For low density lipoproteins cholesterol, a significant difference was found between DM1 + AIT and control groups. Age-independent impact of AIT on CCA_PI was confirmed by multivariate analysis. Common carotid pulsatility is deteriorated by autoimmune thyroiditis independently of age in children with type 1 diabetes mellitus.

Serum Selenium, Iron, Zinc, and Copper Concentrations in Renal Transplant Recipients Treated with Mycophenolate Mofetil.

There are data available in the literature on bioelement concentrations in the serum of various groups of patients; however, very little is known about the serum concentration of selenium (Se), iron (Fe), zinc (Zn), and copper (Cu) in renal transplant patients treated with immunosuppressive drugs, including mycophenolate mofetil (MMF). Monitoring of serum bioelement concentrations in renal transplant recipients is of profound importance, as the proper bioelement levels seem to prolong the normal function of the transplanted organ. Thus, the aim of this current study was to examine and carry out comparative analysis involving serum concentrations of Se, Fe, Cu, and Zn of renal transplant recipients treated with MMF and without MMF. The material consisted of blood samples from 115 patients of the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University, in the city of Szczecin in the northwestern Poland. Serum Se, Fe, Cu, and Zn levels were quantified by inductively coupled mass spectroscopy (ICP-MS). Taking into account all patients, MMF increases Cu level. Cu and Fe concentrations were significantly higher in women treated with MMF; in group of younger patients treated with MMF, Se level was significantly lower comparing with those whose regimen did not include MMF. Additionally, MMF in combination with prednisone increased Se concentration in blood of transplant recipients. Our study highlights that trace elements should be monitored to allow for an early detection of trace elements deficits, which can easily be corrected for by an adjusted diet or supplemental intake.

Association of FGF19, FGF21 and FGF23 with carbohydrate metabolism parameters and insulin resistance in patients with chronic kidney disease.

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function.

Evaluation of parental awareness of children's obesity-related health risk in Poland: survey study.

INTRODUCTION: 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. AIM: 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 Swietokrzyskie Voivodships in Poland. MATERIAL AND METHODS: The questionnaire-based survey was conducted in 2019 during parent-teacher meetings in public schools in the Pomeranian, Lubelskie and Swietokrzyskie Voivodeships Statistical analysis was then performed on the 277 received questionnaires using Statistica 13.3 software package and spreadsheet editor Microsoft Excel 2018. RESULTS: 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. CONCLUSIONS: 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.

Assessment of Sclerostin and Interleukin 6 Levels and Selected Anthropometric Parameters in Patients Receiving Hemodialysis Replacement Therapy-Pilot Study.

Background and Objectives: Chronic kidney disease (CKD) is an important public health problem associated with, e.g., progressive renal insufficiency, bone mineral disorders, and increased inflammatory marker levels. The objective of this study was to compare selected biochemical parameters and to evaluate potential correlations between selected anthropometric parameters and levels of sclerostin and interleukin 6 (IL-6) in blood plasma. Materials and Methods: The study group consisted of 34 patients aged 59.8 ± 9.8 years, receiving hemodialysis therapy. The control group consisted of 31 individuals aged 55.4 ± 9.37 years, presenting with GFR (glomerular filtration rate) of more than 60 mL/min/1.73 m2. Selected anthropometric and biochemical parameters were assessed at baseline, as well as 3 and 6 months into the study. Statistical analyses were performed using the Statistica 2014 software package (StatSoft, Inc.Tulsa, OK, USA). Analyses included descriptive statistics, intergroup comparisons using the Mann-Whitney U-test or the Kruskal-Wallis test, and Spearman's correlation analysis. The significance level was set at p ≤ 0.005. Results: At all measurement time points, i.e., at baseline, at month 3, and at month 6, the IL-6 levels in the study group were significantly higher than those in the control group. No correlations were observed in the study group between SCL or IL-6 levels and anthropometric parameters such as body weight, body mass index (BMI), or waist circumference. Conclusions: Patients receiving hemodialysis replacement therapy present with significantly higher levels of IL-6 in their blood. Anthropometric parameters (body weight, BMI, and waist circumference) have no impact on sclerostin and IL-6 levels in patients undergoing hemodialysis therapy. The results obtained are satisfactory, and the research will be continued.

Successful Salvage Haploidentical Alpha-Beta T Cell-Depleted Stem Cell Transplantation After Busulfan-Based Myeloablation in a Patient With IPEX Syndrome: A Case Report.

BACKGROUND: X-linked immunodysregulation syndrome with polyendocrinopathy and enteropathy (IPEX) is caused by FOXP3 gene mutations that block the generation of regulatory T lymphocytes. We report an 18-month-old boy with classic IPEX who underwent 2 hematopoietic stem cell transplantations (HSCTs). METHODS: The first HSCT from an unrelated 8/10 HLA-matched umbilical cord blood donor (UCB) was performed after a conditioning regimen consisting of treosulfan, fludarabine, thiotepa, and thymoglobulin. Due to complete rejection of the UCB transplant, a second transplantation from a 6/10 HLA-matched mother was performed after alpha-beta T-cell depletion. The second conditioning regimen consisted of busulfan, fludarabine, a single dose of cyclophosphamide 1 g/m2, and Grafalon (Neovii Pharmaceuticals, Rapperswil, Switzerland). The T-cell depletion product contained 15.06 x 106 CD34+ cells per kilogram body weight (BW) and 4.19 x 105 alpha-beta T lymphocytes per kilogram BW. Due to acute graft rejection, the boy was treated with thymoglobulin, and full donor chimerism in both T lymphocytes and mononuclear cells was achieved. The immunosuppressive therapy was stopped 1 year after transplantation. To date, the patient remains free from graft-vs-host disease (GVHD) and immunosuppression. CONCLUSIONS: HSCT after busulfan-based reduced-toxicity conditioning in patients with IPEX syndrome is feasible and well tolerated and can result in full donor engraftment. Monitoring of chimerism and aggressive therapy in cases of graft rejection are warranted due to the high reactivity of residual autologous T lymphocytes. T-cell depletion reduces the risk of GVHD and the need for steroid therapy, which is especially challenging in patients with diabetes.

The Role of MicroRNAs in Selected Forms of Glomerulonephritis.

Glomerulonephritis (GN) represents a collection of kidney diseases characterized by inflammation within the renal glomeruli and small blood vessels. The lesions that occur in other nephron structures mainly result from the harmful effects of proteinuria. In recent years, an emphasis has been placed on gaining a better insight into the pathogenesis and pathophysiology of GN in order to facilitate diagnoses and provide efficient and targeted treatments of the disease. Owing to the advanced molecular and genetic diagnostic techniques available today, researchers have been able to elucidate that most cases of GN are determined by genetic risk factors and are associated with the abnormal functioning of the immune system (the immunologically mediated forms of GN). MicroRNAs (miRNAs) are a group of single-stranded, non-coding molecules, approximately 20 nucleotides in length, that act as regulatory factors in the post-transcriptional processes capable of regulating the expression of multiple genes. In this paper we present the available research aiming to determine effects of miRNAs on the development and progression of GN and discuss the potential role of miRNAs as new diagnostic markers and therapeutic targets.

Poly-ADP-ribose polymerases (PARPs) as a therapeutic target in the treatment of selected cancers.

Introduction: The implementation of poly-ADP-ribose polymerase (PARP) inhibitors for therapy has created potential treatments for a wide spectrum of malignancies involving DNA damage repair gene abnormalities. PARPs are a group of enzymes that are responsible for detecting and repairing DNA damage and therefore play a key role in maintaining cell function and integrity. PARP inhibitors are drugs that target DNA repair deficiencies. Inhibiting PARP activity in cancer cells causes cell death. Areas covered: This review summarizes the role of PARP inhibitors in the treatment of cancer. We performed a systematic literature search in February 2019 in the electronic databases PubMed and EMBASE. Our search terms were the following: PARP, PARP inhibitors, PARPi, Poly ADP ribose polymerase, cancer treatment. We discuss PARP inhibitors currently being investigated in cancer clinical trials, their safety profiles, clinical resistance, combined therapeutic approaches and future challenges. Expert Opinion: The future could bring novel PARP inhibitors with greater DNA trapping potential, better safety profiles and improved combined therapies involving hormonal, chemo-, radio- or immunotherapies. Progress may afford wider indications for PARP inhibitors in the treatment of cancer and the utilization for cancer prevention in high-risk mutation carriers. Research efforts should focus on identifying novel drugs that target DNA repair deficiencies.

Putative loss of CD83 immunosuppressive activity in long-standing complication-free juvenile diabetic patients during disease progression.

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.

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages.

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 impact of autoimmune thyroiditis on skin microcirculation in children with non-complicated type 1 diabetes mellitus.

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.

The cost-effectiveness of screening strategies for familial hypercholesterolaemia in Poland.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) elevates the cholesterol level and increases the risk of coronary events and death. Early detection and treatment reduce this risk. We aimed to determine the cost-effectiveness of FH screening in Poland in children, first job takers, and after an acute coronary syndrome (ACS) event, each followed by a cascade screening in the relatives of the positively-diagnosed subjects. METHODS: A decision tree was constructed to model the diagnosis process. We considered scenarios with and without genetic testing. A life-time Markov was built to investigate the effectiveness (life years gained, LYG; and quality-adjusted life years, QALY) and cost (public payer perspective) of treatment in FH-affected subjects. The clinical benefits result from early treatment reducing the risk of coronary heart disease (and death, in result). Model parameters were based on published data and experts' opinions. The costs (patients visits, tests, drugs) were estimated from the National Health Fund data and other publicly-available sources. RESULTS: Screening ACS patients below 55/65 years of age in men/women is the most cost-effective strategy: the cost of one LYG (QALY) amounts to 100 EUR (110 EUR). Removing the age limit or using genetic tests reduced cost-effectiveness; nonetheless, all strategies remained cost effective: the cost of one LYG or QALY was <5040 EUR, much lower than the official threshold of ca. 29,800 EUR/QALY. CONCLUSIONS: Screening for FH is highly cost-effective in Poland. The strategies are complementary, and using a combination thereof is recommended.

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-α gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-α), proangiogenic factors (VEGF, angiogenin), 17ß-estradiol, values of monocyte subsets (CD14++CD16- and CD14+CD16+), lipid profile, and blood pressure. In our study, girls with CC genotype had lower level of inflammatory and angiogenic factors and lower frequencies of CD14+CD16+ monocytes in comparison to CT or TT carriers. Simultaneously, the CC carriers had a greater population of CD14++CD16- monocytes, increased blood pressure, and serum levels of: estrogen, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than girls bearing CT or TT genotype. Our study suggests a pleiotropic effect of PvuII polymorphic CC variant on diabetic vasculopathies. Although the CC genotype carriers demonstrate less inflammatory and angiogenic activity, they seem to display less favorable cardiometabolic features. Based on our study, we cannot distinguish PvuII ER-α genotype that could be useful in identification of DM1 girls that are more prone to develop of late vascular complications, before the occurrence of first clinical symptoms.

[Steroid-induced diabetes in the paediatric population].

Steroid-induced diabetes is a rare disease in the paediatric population. High doses of corticosteroids are used in diseases such as acute lymphoblastic leukaemia (ALL), lymphomas, or connective tissue diseases. Post-steroid hyperglycaemia arises as a result of increased gluconeogenesis and increased glycogen synthesis. Steroid-induced diabetes most often is asymptomatic; therefore it is important to monitor the glycaemic level in patients receiving systemic glucocorticoids. So far, no separate guidelines for steroid-induced diabetes have been developed, so the criteria for diagnosing drug-related diabetes mellitus do not differ from the criteria for diagnosing type 2 diabetes. Hyperglycaemia adversely affects the immune system: it impairs the function of granulocytes, immunoglobulins, and also causes T-lymphocyte apoptosis. A hyperglycaemic environment favours the development of bacterial and fungal infections. Numerous studies confirm that hyperglycaemia increases the risk of infection and severity of infection. There have also been reports of adverse effects of steroid-induced hyperglycaemia in the course of treatment for the underlying disease in the adult population. Reports related to the paediatric population are not as numerous. There are studies that have proven an increased risk of infection in paediatric patients with ALL and steroid-induced diabetes, as well as studies that proved an unfavourable effect of diabetes on survival in children with ALL and as well the studies that proved that risk of life-threatening infection and survival does not differ statistically in the group of patients with hyperglycaemia and in the group of patients who did not develop diabetes.

[Papillary thyroid carcinoma in a patient with Turner syndrome treated with human growth hormone].

Thyroid cancer is a rare pathology in childhood and adolescence, being responsible for 1.5-3% of all carcinomas in this age group. Differentiated thyroid carcinoma is the most commonly found variant, especially papillary carcinoma of the thyroid (PCT). Currently available data support the hypothesis that growth hormone (GH) as well as insulin-like growth factor 1 (IGF-1) can facilitate carcinogenesis. There is a confirmed role of the GH/IGF-1 axis in cancer progression as an initiator of tumorigenesis and neoplastic transformation, metastasis, and resistance to chemotherapy and radiotherapy. Presently, application of recombinant GH is an acceptable method to treat female patients with growth failure during the course of Turner syndrome (TS). This article reports the case of a fourteen-year-old female patient with Turner syndrome, Hashimoto thyroiditis, and papillary thyroid carcinoma diagnosed during GH treatment. The immunochemical analysis of tumour tissue in our patient revealed intensive brown reaction that labelled expression of the IGF-1R vs. traced reaction or its lack in normal thyroid tissue. A significant role is played by IGF-1 in the pathogenesis of invasion of thyroid cancer; however, this effect is complex, and how it works is not well established.