Skin oxygenation impairment is associated with increased total cholesterol level in children with short-lasting type 1 diabetes mellitus.

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.

Monitoring the Effects of Hypolipidemic Treatment in Children with Familial Hypercholesterolemia in Poland.

Familial hypercholesterolemia (FH) is the most common monogenic autosomal dominant disorder. FH results in an increased cardiovascular mortality rate. However, cardiovascular risk control factors enable the avoidance of approximately 80% of strokes and cardiovascular diseases. Therefore, early detection and implementation of lipid-lowering treatment is essential. In the present study, 57 pediatric patients aged 9.57 ± 3.26 years with FH were enrolled in the study. Researchers checked the lipid profile and performed the ultrasound imaging including intima-media thickness (IMT) measurement and echo (e)-tracking in the study group. Patients were treated with a low-cholesterol diet solely or along with pharmacological treatment with statins. Subsequently, patients were monitored for 12 months. The positive results of dietary treatment were observed in 40 patients. The efficacy of 12 months of nutritional therapy along with pharmacological treatment was reported in 27 patients. We observed a significant decrease in the carotid beta index stiffness and an insignificant decrease in the IMT in the group of patients treated with statins. The obtained data show that statin therapy in children with FH allow for the reduction of the degree of atherosclerotic vessel changes.

Gaseous Pollutants and Particulate Matter (PM) in Ambient Air and the Number of New Cases of Type 1 Diabetes in Children and Adolescents in the Pomeranian Voivodeship, Poland.

The increase in type 1 diabetes mellitus (T1DM) incidence in children is worrying and not yet fully explored. It is suggested that probably air pollution exposure could contribute to the development of T1DM. The aim of the study was to investigate the relationship between the concentration of gaseous pollutants including, nitrogen dioxide (NO2), nitric oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), and particulate matter (PM) in the air, and the number of new cases of T1DM in children. The number of new cases of T1DM was obtained from the Clinic of Paediatrics, Diabetology, and Endocrinology, Medical University of Gdansk. The number of children of 0-18 years old in Pomeranian Voivodeship was acquired from the Statistical Yearbook. The concentrations of PM10 absorbance, NO2, NOx, SO2, and CO were measured at 41 measuring posts, between 1 January 2015 and 31 December 2016. It was detected that the average annual concentration of PM10 was higher than the value acceptable to the WHO. Furthermore, the average 24-hour concentration of PM10 was 92 µg/m3 and was higher compared to the acceptable value of 50 µg/m3 (acc. to EU and WHO). Moreover, the number of new cases of T1DM showed a correlation with the annual average concentration of PM10 (ß = 2.396, p < 0.001), SO2 (ß = 2.294, p < 0.001), and CO (ß = 2.452, p < 0.001). High exposure to gaseous pollutants and particulate matter in ambient air may be one of the factors contributing to the risk of developing T1DM in children. Therefore, it is important to take action to decrease air pollutant emissions in Poland. It is crucial to gradually but consistently eliminate the use of solid fuels, such as coal and wood in households, in favour of natural gas and electricity. The development of new technologies to improve air quality, such as "best available techniques" (BAT) or renewable energy sources (water, wind, and solar generation) is of critical importance as well.

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.

Skin microvascular circulation is not affected by diabetes duration in young patients with non-complicated type 1 diabetes mellitus.

INTRODUCTION: Skin microcirculation is recognized as an appropriate model to use when investigating the relationship between cardiovascular risk factors and microvascular function. It is currently a matter of debate whether studies on skin microcirculation in young type 1 diabetic patients without existing microangiopathy may be helpful in identifying subjects with impaired endothelial function. AIM OF THE STUDY: To evaluate the potential changes in skin microcirculation of patients up age of 18 years using capillaroscopy, post reactive hyperaemia (PORH) and venous occlusion (VO) tests, and to establish the relationship between those changes and disease duration and metabolic control in patients with type 1 diabetes. MATERIAL AND METHODS: Study group consisted of 112 pediatric patients aged 8.4-18.0 years, with a median age of 14.95 years. The median diabetes duration and age at onset were 5 years and 9.6 years, respectively. The median HbA1c in the studied group was 7.6% at the time when the microcirculation was being examined. Capillaroscopy studies were focused on type 1 diabetic patients and employed non-selective stimuli such as the PORH and VO tests. The relative area covered by capillaries (coverage) was measured before the testing and again after the PORH and VO tests. RESULTS: The analysis revealed that none of the skin microcirculation indices correlated significantly with patient age, diabetes duration or metabolic control. CONCLUSIONS: In young patients with uncomplicated type 1 diabetes mellitus skin microcirculation function is not dependent on age, disease duration or metabolic control.

Neonatal outcome and diabetes course in children with GCK-MODY born from women with GCK-MODY.

INTRODUCTION: Gestational diabetes is one of the most common medical disorders and may cause numerous of maternal and foetal complications, such as: preterm births, congenital defects, hypertrophic cardiomyopathy, metabolic changes, and macrosomia in neonates. One of the types of diabetes that may clinically manifest in pregnancy is GCK-MODY, caused by mutations in the glucokinase (GCK) gene. AIM OF THE STUDY: The aim of the study was to assess the impact of diabetes during pregnancy in women with GCK-MODY on their children's health outcome and to determine the clinical and biochemical characteristics of children delivered by patients with GCK-MODY. MATERIAL AND METHODS: Study was multicentre, involving 50 children from paediatric diabetology departments in Gdansk, Katowice, Bialystok, and Lodz. The risk of GCK-MODY was evaluated on the basis of the medical history of the patient, the clinical course of the disease, and laboratory tests performed during diagnostic procedures. Data concerning family history, mothers' health status, course of pregnancy, and perinatal period was collected. RESULTS: The study showed that among children with glucokinase mutation, born by mothers affected with GCK-MODY, 62% received 10 points in Apgar score in the first minute of life, whereas 92% (n = 46) obtained 10 points in Apgar score in the fifth minute of life. The average age of diagnosis of GCK-MODY in children was 8.25 ±4.76 years, and the average HbA1c during diagnosis was 6.43 ±0.71%. Statis-tically significant difference between the absence of macrosomia (birth weight > 91st percentile) in children with GCK-MODY diabetes in comparison to the general paediatric population (p = 0.0229) was observed. CONCLUSION: According to the presented study, possible consequences of GCK-MODY during pregnancy on foetal development are generally less severe and may differ from those characteristic for other types of diabetes. Children born by mothers with diabetes should be followed up regarding glucose disorders. Further investigation of particular phenotypes of GCK-MODY, depending on the type of inherited mu-tation in mothers and their children, is required.