Monogenic diabetes prevalence among Polish children-Summary of 11 years-long nationwide genetic screening program.

BACKGROUND: Estimated monogenic diabetes (MD) prevalence increases as screening programs proceeds. OBJECTIVE: To estimate prevalence of MD among Polish children. SUBJECTS: Patients and their family members suspected of suffering from MD (defined as causative mutation in one of the Maturity Onset Diabetes of the Young or permanent neonatal diabetes mellitus genes) were recruited between January 2005 and December 2015. METHODS: Nationwide prevalence was estimated based on data from 6 administrative provinces (out of 16 in Poland) with high referral rates of patients (>10 per 100 000 children). RESULTS: During the analysis, probands from 322 of 788 screened families tested positive yielding a total of 409 children and 299 family members with MD. An average of 70 probands/year were referred. Screening success rate reached 40% over the study period. We estimated the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence estimates increased nearly 2-fold since our report in 2011 (4.4/100 000). However, the figure reached a plateau because of screening saturation in 2014 what was also proven by lowering of the median age of diagnosis lowered in time (R = -0.73, P = .0172) along with shortening of the delay between clinical and genetic diagnosis (R = -0.65, P = .0417). CONCLUSIONS: The screening for childhood MD in Poland reached a plateau phase after 10 years showing a stable prevalence estimate. The true frequency of MD in the overall population may be higher given later onset of reportedly more frequent types of MD than GCK -MODY.

[Epidemiology of diabetes type 1 in children aged 0-14 in Podlasie Province in years 2005-2012]. / Epidemiologia cukrzycy typu 1 wsród dzieci w wieku 0­14 lat w makroregionie podlaskim w latach 2005­2012.

INTRODUCTION: Epidemiological studies performed during last decades in many European countries and in the world proved increasing incidence rate of diabetes, especially diabetes type 1 in children (DMT1). In Europe there is one of the highest diabetes incidence rate. The aim of the study was to estimate the incidence rate of diabetes type 1 in children aged 0-14 years in North-East Poland during 2005-2012 years and to analyse this rates in relation to age, gender and season of the diabetes onset. PATIENTS AND METHODS: The study was performed among patients staying under care of outpatient diabetes clinic of the Department of Pediatric, Endocrinologym Diabetology with Cardilogy Division, medical University of Bialystok, Poland. The DMT1 incidence rate was calculated as the number of all newly diagnosed cases per 100 000 persons 0-14 aged matched. RESULTS: During the studied 8-years- period DMT1 was diagnosed in 306 children aged 0-14 years, 159 boys and 147 girls, in Podlasie Province. The highest number of new cases was found in 2011: 49, and 2012: 47, with the lowest number in 2005 and 2009: 32 each year. The average incidence rate in the studied period was 20,84/100 000 population, aged matched. The lowest incidence rate was found in 0-4 yrs old group: 14,59 /100 000, in 5-9 years old group was: 22,04/100 000, and was highest in 10-14 years old group: 24,94/100 000. The highest increase in incidence rate was noted in the youngest group: from 9,14/100 000 in 2005, to 23,45/100 000 in 2012. The greatest number of new recognisions was found in from November to March, and the lowest number from June to August. CONCLUSIONS: 1. The DMT1 incidence rate among children aged 0-14 years, in Podlasie Province, during 2005-2012 years was 20,84/100 000. 2. Increase in incidence rate was observed in the studied period from 15,23/100 000 in 2005 to 26,71/100 000 in 2012. The highest increase in incidence rate, 2,5 times, was fund in the youngest group, aged 0-4 years. 3. The seasonal incidence of New onset was observed with the greater number in autumn-winter months.

[Usefulness of short-term usage of real time continuous glucose monitoring system in achieving metabolic control improvement in adolescents with type 1 diabetes]. / Przydatnosc krótkoterminowego wykorzystania systemu ciaglego monitorowania glikemii w czasie rzeczywistym w uzyskaniu poprawy metabolicznej u nastolatków z cukrzyca typu 1.

INTRODUCTION: Experience with use of real-time continuous glucose monitoring systems (RT-CGMS) in teenagers with diabetes type 1 is limited, and in unselected groups of young patients did not show improvement in metabolic control. AIM OF THE STUDY: The objective of this study was to assess short-term RT-CGMS usage in teenagers with type 1 diabetes, in terms of possibility to improve metabolic control and acceptance of the system. MATERIAL AND METHODS: 40 subjects, aged 14.5±2 years on insulin pump therapy were included in the study. Mean diabetes duration was 6±3 years and HbA1c level before the study was 8.4±1.5%. The analysis was based on single 5-6 days long sensor usage, connected with education of the family. We analysed several parameters of glycaemic variability during the study, and HbA(1)c level before and 2 months after the study. Patients' satisfaction was assessed on the basis of a questionnaire. RESULTS: HbA(1)c level in the whole teenagers group decreased insignificantly by 0.3%; from 8.4±1,% to 8.1±1.6%. In 24 (60%) patients we showed improvement in HbA(1)c by at least 0.5% (mean 0.9%, from 8.1±1.3% to 7.2±1.2%; p=0.03). HbA(1)c level was slightly higher in girls than in boys at the beginning of the study and a greater reduction in HbA(1)c was shown for boys. After two months the difference was significant: 8.6±1.9% in girls vs. 7.6±1.3% in boys, p=0.03. In the group with HbA(1)c decrease and in boys we demonstrated improvement in mean glycaemia and glycaemic variability parameters on the last day of the sensor usage, compared to the first day. In boys however, increased AUC <70 mg/dl/ min was noticed. The patients from the group with HbA(1)c decrease reported fewer problems with system calibration: 3.2 vs. 2.6 score, p=0.03. This group also reported higher satisfaction score connected with new knowledge: 4.0 vs. 3.5, and with quality of life: 4.1 vs. 3.6. CONCLUSIONS: Short-term usage of RT-CGMS, combined with satisfaction questionnaire performed in teenagers with diabetes type 1 can be useful in defining the group of young patients who can benefit from RT-CGMS usage in long-term metabolic control improvement.

[Evaluation of adiponectin level in children and adolescents with diabetes type 1]. / Ocena stezenia adiponektyny u dzieci i mlodziezy z cukrzyca typu 1.

INTRODUCTION: Adipose tissue is not only an energy storage place, but it also secretes numerous "adipocytokines" - substances that have systemic influence. Adiponectin has an anti-inflammatory, antiatherogenic properties and increases insulin sensitivity. It is emphasized that adiponectin levels are different in type 1 and type 2 diabetes. THE AIM OF THE STUDY: was to evaluate adiponectin levels in young patients with diabetes type 1, and to analyse of the correlation between adiponectin and: BMI, lipid parameters, glomerular filtration rate and microalbuminuria. MATERIAL AND METHODS: The study group was formed by 95 patients from the Outpatient Diabetology Department 2nd Department of Children's Diseases, 45 girls and 50 boys, aged from 7 to 20 years (mean - 14.97 yrs) suffering from diabetes from 1 to 17 years (mean 6.68 yrs). Control group consisted of healthy children, age matched, without family history of cardiovascular diseases. In all patients anthropometric measurements were performed (BMI was calculated), metabolic control was evaluated on the basis of HbA1c level, microalbuminuria was studied in 24 hour urine sample. We assessed glomerular filtration rate (endogenous creatinine clearance), lipid parameters and adiponectin level. RESULTS: In children and adolescents with diabetes type 1 we found significantly higher levels of adiponectin compared to control group: 32.72+/-13.49 vs. 26.53+/-7.63 ug/ml; p=0.024. Adiponectin level was higher in girls than in boys (33.56 vs. 28.75 ug/ml; p=0.036). Adiponectin level did not depend on metabolic control and on diabetes duration. We found a statistically significant negative correlation between adiponectin and creatinine (r=-0.26; p=0.011). In patients with diabetic complications we found insignificantly lower adiponectin level compared to patients without complications (30.99+/-14.29 vs. 33.67+/-11.68 ug/ml; p=0.35). CONCLUSIONS: 1. In patients with diabetes type 1 significantly higher level of adiponectin was found compared to healthy control group. 2. Adiponectin level correlated negatively with creatinine level end microalbuminuria. 3. Elevated level of adiponectin in patients without diabetic complications may help to explain the pathogenesis of diabetic angiopathy.

[hsCRP protein in children and adolescents with diabetes type 1]. / Bialko hsCRP u dzieci i mlodziezy z cukrzyca typu 1.

INTRODUCTION: HsCRP protein is known as a novel marker of low grade inflammatory state, which characterises an atherosclerotic process in its early stages. Contrary to a large amount of data on inflammatory markers in diabetes type 2 and metabolic syndrome in adults, little is known so far about the inflammatory process in diabetes type 1, especially in children. The aim of the study was to estimate the level of hsCRP protein in children and adolescents with diabetes type 1 depending on coexisting additional risk factors for atherosclerosis and microvascular complications. MATERIAL AND METHODS: 127 children and adolescents with diabetes duration 6.7+/-3.3 years, aged 14.9+/-3.1, were studied. The control group consisted of 52 healthy children aged 14.9+/-2.8 years, matched acc. to gender. HsCRP level was assessed with use of immunoturbidymetric, latex augmented method (Tina-quant CRP (Latex) HS, Roche). RESULTS: HsCRP in the whole study group was nearly significantly higher compared to control group: 0.17+/-0.2 vs. 0.078+/-0.1 mg/dl, p=0.072. In diabetic hypertensive children (n=38) we found significantly higher levels of hsCRP compared to controls (0.27+/-0.3 vs. 0.07 mg/dl, p=0.008) and compared to diabetic normotensive children (0.13+/-0.22 mg/dl; p=0.024). Diabetic obese patients (n=23) had significantly higer hsCRP compared to controls (0.24+/-0.3 vs. 0.07+/-0.1 mg/dl, p=0.04). In 14 studied diabetic children we found coexisting hypertension and obesity, and we found further increase in hsCRP level - 0.28+/-0.3 mg/dl. In diabetic children with microangiopathy hsCRP level was 0.22+/-0.2 mg/dl, and it was insignificantly higher compared to controls and to diabetic children without complications. Correlation analysis showed interrelations between hsCRP and systolic blood pressure (r=0.2; p=0.04) and HbA1c (r=0.25; p=0.015). In stepwise regression analysis hsCRP was related to systolic blood pressure, HbA1c and the triglycerides level (R=0.37; p=0.003). CONCLUSIONS: In children and adolescents with diabetes type 1 we proved significantly higher levels of hsCRP in case of a coexistence of hypertension and/or obesity. Elevated hsCRP in children with diabetes type 1 and hypertension and/or obesity reflects low grade inflammatory state in the course of metabolic syndrome.

[Does autonomic diabetic neuropathy influence microcirculation reactivity in adolescents with diabetes type 1?]. / Czy autonomiczna neuropatia cukrzycowa wplywa na reaktywnosc mikrokrazenia u mlodziezy z cukrzyca typu 1?

INTRODUCTION: Microcirculation is known to be disturbed in many organs of diabetic patients. Retinopathy, nephropathy and neuropathy might be considered as the cause of the functional and morphological changes at the level of microcirculation. The aim of the study was to assess by means of dynamic capillaroscopy the influence of autonomic diabetic nephropathy (CAN) in adolescents with type 1 diabetes mellitus on capillary blood flow (CBV) in skin microcirculation. MATERIAL AND METHODS: The study group consisted of 18 patients with type 1 diabetes mellitus (mean age 15+/-2 years). In 9 of them the diagnosis of CAN was made on the basis of Ewing tests. The control group consisted of 10 healthy persons aged 15+/-1.5 years. CBV was measured in capillars of the nailfold of the fourth finger during rest and after 2 minutes of arterial occlusion (the occlusion pressure - above 20 mmHg systolic blood pressure - was obtained by the occlusion of brachial artery using sphygnomanometer cuff). RESULTS: The resting CBV did not differ between patients with CAN, without CAN and healthy controls (0.39+/-0.06, 0.41+0.05 i 0.42+/-0.07). The values of the peak CBV significantly differ between the examined groups (CAN: 0.75+0.1; without CAN: 0.86+/-0.11; control group: 0.98+/-0.09, p<0.01). CONCLUSIONS: The obtained results indicate that the presence of the autonomic diabetic neuropathy significantly influences the regulatory function of microcirculation, which may predispose to occurrence of different late diabetic complications.

[Evaluation of central corneal thickness in children and adolescents with type I diabetes mellitus]. / Analiza centralnej grubosci rogówki u dzieci mlodziezy z cukrzyca insulinozalezna.

PURPOSE: To evaluate corneal thickness in diabetic and nondiabetic patients. MATERIALS AND METHODS: The central corneal thickness (CCT) was investigated in 100 eyes of 100 patients with diabetes type I and in 99 nondiabetic patients (99 eyes). The mean diabetic patients age was 15.31 +/- 3.18 years. The mean age in control group was 14.3 +/- 2.2 years. Corneal thickness was measured by non-contact microscope Topcon SP-2000P Statistical analysis was performed to assess systemic factors (patient age, sex, duration of diabetes mellitus, hemoglobin A1c value, diabetes control) related to CCT. SAS STAT (Release 8.2) program, the independent t-test, Kolmogorow-Smirnow test and Bartlett test were used to compare differences between the diabetic and control group. RESULTS: In our study the mean CCT in diabetic eyes was 0.54 +/- 0.03 mm and was significantly increased, compared to control group (0.525 +/- 0.037 mm). None of systemic factors was correlated with CCT. CONCLUSIONS: Our findings indicate that diabetes mellitus affects thickness of cornea in adolescents. Evaluation of endothelium in specular microscope should be performed in the diabetic patients.

[Metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 levels in children and adolescents with type 1 diabetes]. / Aktywnosc metaloproteinaz MMP-2 i MMP-9 oraz ich inhibitorów TIMP-1 i TIMP-2 u dzieci i mlodziezy z cukrzyca typu 1.

INTRODUCTION: Abnormal activation of the matrix metalloproteinases (MMPs) in diabetes mellitus leads to extracellular matrix changes through the structural protein composition changes. The metalloproteinases inhibitors (TIMPs) are regulatory factors in this activity. Not all regulating mechanisms are completely known, especially in patients with type 1 diabetes. THE AIM OF STUDY: evaluation of MMP-2, MMP-9 and TIMP-1, TIMP-2 levels in children and adolescents with type 1 diabetes. MATERIAL AND METHODS: 74 patients in the mean age 15 years (+/-3.0) suffering from type 1 diabetes for mean 6.6 years (+/-3.6) took part in the study. Patients were treated with flexible multiple daily insulin (n=54) and with continuous subcutaneous insulin infusion - personal insulin pump (n=20). MMP-2, MMP-9, TIMP-1 and TIMP-2 blood serum levels were measured in all patients. 45 healthy persons matched for age, without atherosclerosis risk factors, with proper BMI and lipids levels were in the control group. RESULTS: MMP-2 level as well as TIMP-2 and TIMP-2 levels were significantly higher in patients with type 1 diabetes in comparison to the control group (p respectively <0,01; <0,02; <0,001). We observed higher MMP-9 level in obese patients than in patients with BMI value below 90 pc for sex and age (p<0,02). We noted lower MMP-2 level in patients with chronic complications and/or arterial hypertension (n=24) in comparison to patients without that kind of complications (p<0,05). Positive correlation between TIMP-1 level and HbA1c level was noted. Age of patients as well as BMI negatively correlated with MMP-2 and TIMP-2 and positively with TIMP-1. We observed a correlation between MMP-2, TIMP-2 and especially TIMP-1 with lipid levels. Strong positive correlation was noted between MMP-2 and TIMP-2 (r=0.8; p<0,0001). CONCLUSIONS: 1. MMP-2, TIMP-1 and TIMP-2 levels are higher in patients with type 1 diabetes than in the control group. 2. Age, diabetes duration, metabolic control, BMI and lipids levels have influence on the MMPs/TIMPs system. 3. TIMP-1 is supposed to be the key marker of metabolic disturbances in type 1 diabetes.

[Ultrasonographic evaluation of selected parameters of the endothelial function in brachial arteries and IMT measurements in carotid arteries in children with diabetes type 1 using personal insulin pumps--preliminary report]. / Ultrasonograficzna ocena wplywu zastosowania osobistych pomp insulinowych na stopien zaawansowania procesu miazdzycowego w tetnicach szyjnych wspólnych i ramiennych u dzieci z cukrzyca typu 1--doniesienie wstepne.

INTRODUCTION: Type 1 diabetes is a known risk factor for arterial atherosclerosis. The first symptoms can be found even in childhood. The ultrasonographic measurements of intimal plus medial thickness in carotid arteries (IMT) and flow mediated dilatation (FMD) evaluated in brachial arteries, play a known role in the detection in these cases. The diabetes treatment intensification is an important factor in delaying early atherosclerotic changes. Currently, intensive treatment of children's diabetes with use of continuous subcutaneous insulin infusion with personal insulin pumps is gaining more and more popularity. THE AIM OF THIS STUDY was the evaluation of IMT and FMD indexes in children suffering from type 1 diabetes in the context of treatment intensification (multidose insulin injections v. personal insulin pumps). MATERIAL AND METHODS: We examined 64 children (29 boys and 35 girls) in the mean age 15.5 years treated with the multidose insulin injections method and 10 children using personal insulin pumps (4 girls and 6 boys) in the mean age 14.5 years. Using high resolution ultrasonography we evaluated IMT values in carotid arteries and FMD parameters in brachial arteries. In our analysis we estimated the blood concentration of lipid parameters, values of systolic and diastolic blood pressure, the age of diabetes onset, duration time of the illness and the values of HbA1c as a marker of metabolic control. RESULTS: We noticed significantly higher FMD values in patients treated with personal insulin pumps (13.7 vs. 5.5%, p=0.001). IMT values were similar in both groups (0.52 vs. 0.5 mm, p=0. 41). The level of HDL cholesterol was higher and triglycerides lower in the group with treatment intensification. The metabolic control was the same in both groups. In patients treated by the multidose insulin injections IMT correlated with systolic blood pressure values. We didn't notice any correlation between IMT and FMD in any group. CONCLUSIONS: 1. Treatment intensification (personal insulin pumps) influences better vascular endothelial function in type 1 diabetic children and seems to be a significant tool in delaying the atherosclerotic process. 2. We need more examinations to explain the role of treatment intensification in common carotid arteries wall morphology in type 1 diabetic children. 3. The ultrasonographic detection of atherosclerotic changes in arterial vessels can help in the evaluation of the changes due to different methods of diabetes treatment.

[The assessment of 24-hour ambulatory blood pressure monitoring (ABPM), microalbuminuria and diabetic autonomous neuropathy in children with type 1 diabetes and hypertension]. / Ocena 24-godzinnego monitorowania cisnienia tetniczego, mikroalbuminurii oraz autonomicznej neuropatii cukrzycowej u dzieci z cukrzyca typu 1 i nadcisnieniem tetniczym.

INTRODUCTION: The late complications of diabetes consisted of autonomic neuropathy, nephropathy, which more often coexist with hypertension in children with type 1 diabetes mellitus. THE AIM OF THE STUDY was to assess the connections between changes in the autonomous nervous system, 24-hour ABPM and daily albumin excrection in children with hypertension and type 1 diabetes mellitus. MATERIAL: The group consisted of 72 patients with diabetes (diabetes duration time 6.5+/-1.5 years). 34 patients of that group have hypertension. The control group consisted of 30 healthy children matched according to age and sex. RESULTS: In children with hypertension we found significantly often occurrence of microalbuminuria (13/34 i 1/38, p<0.001). In 17 patients from the group with hypertension and 17 patients without hypertension we affirm signs of autonomic neuropathy. The values of heart rate variability (HRV) were significantly decreased in the group with hypertension as compared to the control group. A stepwise multiple regression analysis with hypertension as a dependent variable and diabetes duration time, microalbuminuria, HbA1c level, HRV parameters and a presence of autonomous neuropathy as predictors proved that hypertension is associated with higher HbA1c level (b=0.35), the presence of autonomous neuropathy (b=0.28), and lower HF values (b=0.41) (p<0.01). CONCLUSIONS: Hypertension in children with type 1 diabetes mellitus is correlated with the presence of autonomous neuropathy, higher HbA1c level and lowered values of heart rate variability parameters.

[Is soluble thrombomodulin a molecular marker of endothelial cell injury in children and adolescents with arterial hypertension?]. / Czy rozpuszczalna trombomodulina (STM) jest markerem uszkodzenia sródblonka naczyn u dzieci i mlodziezy z nadcisnieniem tetniczym?

INTRODUCTION: Endothelial damage is an early step in the pathogenesis of atherosclerosis which begins in early childhood after exposure to atherogenic risk factors such as arterial hypertension. Atherosclerosis is becoming a common disease even in children and adolescents. Its progression may lead to very severe cardiovascular complications. Thrombomodulin (TM), a specific marker of endothelial cell damage, is a transmembranous glycoprotein with vasoprotective and anti-coagulant properties. TM-thrombin complex becomes an activator of protein C which inactivates factor Va and VIIIa and thereby inhibits the blood coagulation cascade. TM may be cleaved to its soluble (sTM) form by proinflammatory mediators and then detected in the circulation. AIM: The aim of the present study was to investigate if sTM plasma concentration--one of biochemical markers of endothelium injury--is higher in children and adolescents with arterial hypertension (AH). MATERIALS AND METHODS: We studied 32 children with hypertension (9 girls and 23 boys, age range 10.5-17.2 years), and 17 healthy controls, without family history of cardiovascular diseases. Hypertension was detected after 24 hrs ABPM (Ambulatory Blood Pressure Monitoring). We measured plasma concentration of sTM, blood lipids profile, body mass index (BMI) and, as sTM is excreted by the kidney, we also measured plasma level of creatinine and its clearance. RESULTS: Plasma concentration of sTM in the group with essential hypertension was significantly higher than that in the control group (4.01 +/-1.05 vs 3.42+/-0.4; p<0. 05). There were no significant associations between sTM and age or sex. Analyzing lipids profile (cholesterol, LDL-c, HDL-c, triglycerides) we did not find any differences in their levels between groups. We observed statistically significant correlation between sTM and systolic and diastolic blood pressure during the day and night. In addition BMI ratio was higher in AH group but there was no significant correlation between sTM and BMI. CONCLUSION: Statistically higher level of sTM in children with AH compared with healthy individuals makes us sure that endothelium cells, even in children who were shortly exposed to atherogenic risk factors such as essential hypertension, are noticeably damaged. These results constitute an additional signal that a lot of effort should be put into the endeavors to eliminate atherogenic risk factors in children in order to prevent cardiovascular events.

Heart rate variability and left ventricular mass in slim children and young adults with hypertension.

INTRODUCTION: Uncontrolled arterial hypertension brings direct and long-term sequelae in adult age, such as stroke, ischaemic heart disease with myocardial infarction, left ventricular hypertrophy or cardiac arrhythmia. AIM: To assess heart rate variability (HRV) spectral parameters and left ventricular mass in slim children with arterial hypertension, and to search for correlations between these two parameters. METHODS: 35 children aged 14.4+/-3.1 with idiopathic untreated arterial hypertension were enrolled. The control group included 30 age- and gender-matched healthy children (aged 14.1+/-2.9 years). In all analysed subjects an analysis of HRV parameters (high frequency (HF) and low frequency (LF) components) during 10-minute waking state and sleeping time was performed and left ventricular mass (LVM) as well as the left ventricular mass index (LVMI, g/m) were assessed based on echocardiographic measurements. RESULTS: There was no difference in LF during the waking state and sleep HF between the two groups, whereas HF values during the waking state were significantly lower (p<0.05) in children with hypertension. The LF/HF index from both registration intervals was significantly higher in the group of children with hypertension. In children with hypertension, LVM and LVMI correlated significantly with LF (r=0.32, p<0.05 and r=0.39, p<0.01). LVM and LVMI correlated positively with the LF/HF index during night hours (r=0.45, p<0.004 and r=0.49, p<0.002). No significant correlations were found between the analysed parameters in children from the control group. CONCLUSIONS: The increase of sympathetic activity during sleep correlates significantly with left ventricular mass and corrected left ventricular mass index in children with arterial hypertension.

[Correlation analysis between biochemical and biophysical markers of endothelium damage in children with diabetes type 1]. / Ocena korelacji miedzy biochemicznymi i biofizycznymi markerami uszkodzenia sródblonka u dzieci z cukrzyca typu 1.

UNLABELLED: Endothelial damage is one of the earliest stages in the atherosclerosis process. Adhesion molecules, secreted from dysfunctional endothelial cells are considered as early markers of atherosclerotic disease. Ultrasonographic evaluation of brachial arteries serves to detect biophysical changes in endothelial function, and evaluation of carotid arteries intima-media thickness allows to evaluate the earliest structural changes in the vessels. The aim of the study was to the evaluate levels of selected adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin) and endothelial function with use of brachial artery dilatation study (flow mediated dilation--FMD, nitroglycerine mediated dilation--NTGMD) and IMT in carotid arteries in children and adolescents with diabetes type 1, as well as the correlation analysis between biochemical and biophysical markers of endothelial dysfunction. MATERIAL AND METHODS: We studied 76 children and adolescents, with mean age--15.6+/-2.5 years, suffering from diabetes mean 7.8+/-2.8 years, mean HbA1c--8.4+/-1.5%. Control group consisted of 33 healthy children age and gender matched. Adhesion molecules levels were estimated with the use of immunoenzymatic methods (R&D Systems). Endothelial function was evaluated by study of brachial arteries dilation--FMD, NTGMD, with ultrasonographic evaluation (Hewlett Packard Sonos 4500) after Celermajer method, and IMT after Pignoli method. RESULTS: In the study group we found elevated levels of sICAM-1: 309.54+/-64 vs. 277.85+/-52 ng/ml in the control group (p<00.05) and elevated level of sE-selectin: 87.81+/-35 vs. 66.21+/-22 ng/ml (p<00.05). We found significantly impaired FMD in brachial arteries in the study group--7.51+/-4.52 vs. 12.61+/-4.65% (p<00.05) and significantly higher IMT value: 0.51+/-0.07 vs. 0.42+/-0.05 mm (p<00.001). Correlation analysis revealed a significant negative correlation between sE-selectin and FMD - r=-0.33 (p=0.004), and a positive correlation between E-selectin and IMT: r=0.32 (p=0.005). CONCLUSIONS: 1. In children and adolescents with diabetes type 1 we found elevated levels of adhesion molecules sICAM-1 and sE-selectin, what can confirm an endothelial dysfunction in these patients. 2. Significant negative correlation between sE-selectin level and FMD, and positive correlation between sE-selectin and IMT were found. 3. Biophysical proof of this damage is impaired brachial artery dilatation--FMD, and increased IMT values provide information about structural changes in the vessels.

[Usefulness of continuous glucose monitoring system (CGMS) in monitoring glycaemic profile in small children with diabetes type 1]. / Przydatnosc zastosowania systemu ciaglego monitorowania glikemii (CGMS) w ocenie i monitorowaniu profilu glikemii u malych dzieci chorych na cukrzyce typu 1.

BACKGROUND: Improved methods of diabetes therapy result in a near normoglycaemic state in many patients. This leads however unfortunately to more frequent hypoglycaemic incidents. Particularly small children, whose nervous system is not fully mature, are at high risk of central nervous system damage in case of hypoglycaemia. A new method of detail monitoring of glycaemia provides CGMS system. OBJECTIVES: The aim of the study was to compare the glycaemic profile, with high attention to hypoglycaemia in groups of young and older children with diabetes type 1, using CGMS and routine glucose meter. MATERIAL AND METHODS: We studied 32 children with diabetes type 1. Children were divided into groups: group I--small children, n=17 (<7 yrs of age), mean age 5,8 years, with disease duration--2,46 years, with mean HbA1c level--7,22%, and group II--older children, n=15 (>10 years of age), mean age--12 years, with disease duration--3 years, with HbA1c level--7,21%. Continuous glucose monitoring system (CGMS), by MiniMed, was applied in outpatient or hospital conditions, after short training of patient and parents; together with routine glucose meter measurements, 4-8 times/24 hours. In 9 patients from small children group CGMS was repeated after 2 months. RESULTS: Hypoglycaemic incidents detected with CGMS were similar in both groups: 4,6 in I group vs. 4,2 in II group (ns). Hypoglycaemic incidents found with meter were lower in I group--1,6 vs. 2,3 in II group (ns). Mean hypoglycaemic time/24 hour was longer in small children group: 101 min vs. 74 min in group II (p<00,05). In I group we found higher number of hypoglycaemic incidents during the night compared to group II--1,7 vs. 0,8 (p<00,05) and longer duration of night hypoglycaemia: in I group--56 min vs. 32 min in group II (p<00,05). Repeated CGMS study in 9 children from I group revealed decreased mean time of hypoglycaemia/24 hours from 134 min/24 h to 90 min/24 h (p<00,05) and decreased time of night hypoglycaemia from 65 min to 40 min (p<00,05), with a comparable number of hypoglycaemic incidents. Hypoglycaemic incidents found with routine meter measurements in small children were 1,6 vs. 4,6 hypoglycaemia found with CGMS (p<00,05), in the older children group routine measurement found 2,3 hypoglycaemia vs. 4,2 detected with CGMS (ns). CONCLUSIONS: 1. CGMS can be particularly usefull in monitoring glucose profile and detecting hypoglycaemia incidents, mainly nocturnal in small children. 2. CGMS allows to verify meal dose of insulin and to decrease postprandial hyperglycaemia. 3. Modification of insulin therapy on the base of CGMS helps to decrease the time of hypoglycaemia and hyperglycemia, particularly during the night.

[If the level of cystatin C in children and adolescents with type 1 diabetes an early marker for diabetic nephropathy?]. / Czy ocena stezenia cystatyny C u dzieci i mlodziezy z cukrzyca typu 1 moze byc wczesnym markerem nefropatii cukrzycowej?

BACKGROUND: The most important complication in the course of diabetes mellitus type I is diabetic nephropathy. Nowadays, apart from assessing the increased amount of albumins in urine, we are not able to identify early enough these patients whose health might be endangered by nephropathy. Looking for other biochemical indicators which could mark the early symptoms of kidney damage/renal malfunction seems to be justified. OBJECTIVES: 1. What is the concentration of cystatin C among children and teenagers suffering from diabetes mellitus type 1 and whether its level depends on the age of patient, the age in which the patient was affected with the disease, the length of the disease, metabolic compensation, diabetes control and the presence of microangiopathy? 2. Is there any interdependence between cystatin C and microalbuminuria and the renal efficiency rates? MATERIAL: Study group. A group of 130 patients (60 girls and 70 boys aged from 7 and 20,8) who have been suffering from juvenile diabetes from 1 to 17 years was examined. The control group were healthy youngsters, matched for age and sex, without any /burdening/ medical history. METHODS: All the patients were examined in the following way: anthropometric measurements were taken, BMI in kg/m2 was defined, metabolic compensation based on HbA1c (%) was estimated. Ophthalmological examination and a circadian monitoring of arterial blood pressure were carried out. Microalbuminuria in a 24-hour urine collection was determined. In both groups glomerular filtration rate with the help of endogenous creatinine clearance and the concentration of cystatin C were evaluated. The results were subject to statistical analysis. RESULTS: The average age of the whole examined group was 15+/-3,0 the average disease length 6,85+/-3,36 years. The concentration of cystatin C among diabetic patients was higher in comparison with the control group (0.75+/-0.13 vs. 0.68+/-0.12 mg/l). It was also discovered that the concentration of cystatin C was increasing along with the length of the disease reaching the highest level in the group of patients suffering from this disease longer than 10 years (0.52+/-0.11 vs. 0.67+/-0.13 vs. 0.93+/-0.13 mg/l), which is again statistically significant. Moreover the concentration of cystatin C is higher among patients with insufficient diabetes control (0.765+/-0.12 mg/l vs. 0.71+/-0.12 pg/ml, p<0.05). These patients who additionally developed vascular complications (retinopathy, nephropathy, arterial hypertension) had significantly higher condensation of cystatin C (0.75+/-0.13 vs. 0.69+/-0.11 mg/l, p<0.05). DISCUSSION: Having considered the initial results, the following conclusion can be reached: only further, long-term research can supply us with the reliable data whether assessing the level of cystatin C concentration in children's and teenagers' serum in diabetic patients could become the earlier marker of renal malfunction than microalbuminuria.

[Could the expression of L-selectin be an early marker of arterial hypertension and microangiopathy in the course of type 1 diabetes mellitus in juvenile patients?]. / Czy ekspresja L-selektyny moze byc wczesnym markerem nadcisnienia tetniczego i mikroangiopatii w przebiegu cukrzycy typu 1 u mlodocianych pacjentów?

BACKGROUND: Autoreactive T lymphocytes participate in the development of type 1 diabetes mellitus. The migration of T cells is initiated by increased expression of L-selectin on the cellular membrane of lymphocyte. Recently, a correlation between the concentration of sL-selectin and the develop-ment of diabetic retinopathy, atherosclerosis and arterial hypertension was stated. OBJECTIVES: The purpose of this study was to evaluate whether the expression of L-selectin on lymphocytes T alters in the course of the disease -- diabetes lasting less than 5 years and over 5 years; to assess a relationship between the percentage of L-selectin on T cells and the evolution of vascular complications; to elucidate whether the percentage of peripheral blood T lymphocytes expressing L-selectin could be an early marker of angiopathy in juvenile patients. MATERIAL AND METHODS: The study was carried out on 60 children and adolescents (aged 9-20) with diagnosed type 1 diabetes: a) (20 n) with the disease lasting <5 years, b) (20 n) with type 1 diabetes lasting >5 years without vascular complications, c) (20 n) with type 1 diabetes and vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy). The control group consisted of 20 healthy volunteers (aged 6-17). The expression of adhesion molecules has been evaluated by using three-color flow cytometry (Coulter EPICS XL). HbA1c concentration has been analysed by a liquid chromatography technique HPLC-Variant (Bio-Rad). RESULTS: The percentage of T lymphocytes expressing L-selectin was significantly increased in all groups of patients with type 1 diabetes versus healthy controls (p<0.005 and p<0.001, in groups without complications and with angiopathy, respectively). Moreover in patients with diagnosed arterial hypertension the percentage of T lymphocytes expressing L-selectin was higher than in patients in whom arterial hypertension was not developed (p<0.05). CONCLUSIONS: In juvenile patients with type 1 diabetes the percentage of T lymphocytes expressing L-selectin was increased independently on the du-ration of the disease. In children with type 1 diabetes and diagnosed vascular complications the highest percentage of T lymphocytes expressing L-selectin was found.

Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes.

The attachment of monocytes and lymphocytes to endothelial cells, which initiates atherosclerosis, arises under the influence of adhesion molecules. The preclinical phase of this disease lasts many decades, and this provides an opportunity for the presymptomatic detection of high-risk subjects. We evaluated levels of the adhesion molecules: sICAM-1 (soluble intercellular adhesion molecule 1), sVCAM-1 (soluble vascular adhesion molecule 1), sE selectin, sP selectin, and sL selectin in children with atherosclerosis risk factors (n = 123, mean age 15.1 years) (obese [n = 17], hypertensive [n = 25], obese with hypertension [n = 30], type 1 diabetic [n = 51]). Twenty-seven healthy children formed the control group, mean age 15.2 years. sICAM-1 was higher in the study group compared with control (314.1 +/- 61 vs 264.9 +/- 55 ng/mL, P < .01). The same was found for sVCAM-1 (513.7 +/- 187 vs 407.9 +/- 76 ng/mL, P < .05) and E selectin (86.04 +/- 33.6 vs 62.1 +/- 20.3 ng/mL, P < .01). sP-selectin and sL-selectin levels were not different compared with controls. E selectin correlated with body mass index (BMI; r = 0.18, P = .03), total cholesterol (r = 0.2, P = .016), and triglycerides (r = 0.22, P = .008). sICAM-1 correlated with BMI (r = 0.19, P = .019) and systolic blood pressure (r = 0.13, P = .045). In multiple linear regression analysis, sE selectin was found to be associated with triglycerides (R2 = 0.29, P = .045), sICAM-1 dependent on BMI (R2 = 0.58, P = .047), and sVCAM-1 dependent on total cholesterol (R2 = 0.51, P = .006). Elevated concentrations of sICAM-1, sVCAM-1, and E selectin were found in obese, hypertensive, and diabetic children. We conclude that endothelial activation appears in these children, and adhesion molecules are related to the earliest stages of atherosclerosis.

[Soluble thrombomodulin--a molecular marker of endothelial cell injury in children and adolescents with obesity]. / Rozpuszczalna trombomodulina -- marker uszkodzenia sródblonka u dzieci i mlodziezy z otyloscia prosta.

BACKGROUND: Endothelial damage is an early step in the pathogenesis of atherosclerosis which begins in early childhood after exposure to atherogenic risk factors such as obesity. Its progression may lead to very severe cardiovascular complications. TM -- a specific marker of endothelial cell damage, is a transmembranous glycoprotein with anti-coagulant properties. It has a large, extracellular region comprising a thrombin binding site. TM-thrombin complex becomes an activator of protein C which inactivates factor Va and VIIIa and thereby inhibits the blood coagulation cascade. OBJECTIVES: The aim of the present study was to investigate if plasma concentration of sTM (one of markers of endothelial cells injury) is higher in children and adolescents with obesity. MATERIALS AND METHODS: We studied 22 obese children, 11 girls and 11 boys, (age range 8.5-17.8 years), and 17 normal weight healthy controls, (age range 12-17.9 years) without family history of cardiovascular diseases. We measured plasma concentration of sTM, blood lipids profile, body weight and BMI. As sTM is excreted by the kidney we also measured plasma level of creatinine and its clearance. RESULTS: Plasma concentration of sTM in the group with obesity was significantly higher than that in the control group. There were no significant association between sTM and age or sex. Compared with non-obese patients, obese children had higher plasma concentration of total cholesterol, LDL-c, triglycerides, but these were not significant differences. However there was a significantly lower level of HDL-c in children with obesity. In addition statistically significant correlation between sTM and BMI was observed in the obese group. CONCLUSIONS: Statistically higher level of sTM in children with obesity compared with healthy individuals makes us sure that endothelium cells, even in children who were shortly exposed to atherogenic risk factors such as obesity, are noticeably damaged. These results constitute an additional signal that a lot of effort should be put into the endeavors to eliminate atherogenes risk factors in children population in order to prevent cardiovascular events.

[Progression of diabetic retinopathy in patient with Graves' disease]. / Progresja retinopatii cukrzycowej u pacjentki ze wspólistniejaca chorobq Gravesa--Basedowa.

The authors present the case of 16-year old girl with diabetes mellitus type 1. She had progression of diabetic retinopathy because of occurrence of Graves' disease. Surgical intervention (strumectomy subtotal, bilateral), was performed and regression of retinal changes was observed.

[Evaluation of the vascular endothelial growth factor in children and adolescents with type 1 diabetes]. / Ocena stezenia endotelialnego czynnika wzrostu naczyn u dzieci i mlodziezy chorujacej na cukrzyce typu 1.

UNLABELLED: Diabetes type 1 is the chronic disease, leading to many acute and late complications. Pathogenesis of the late complications is not fully understood. Lately, growth factors, and especially vascular endothelial growth factor (VEGF) are gaining great interest as potential risk factors of late diabetic complications, mainly nephropathy and retinopathy The aim of the study was evaluation of the level of VEGF in children and adolescents with diabetes type 1, and searching for correlation between level of this cytokine and microangiopathy and metabolic control. MATERIAL AND METHODS: 68 young diabetic type patients were studied, aged 8-20 yrs (x = 15.54 yrs), suffering from diabetes type 1 from 2.3-16.5 yrs (x = 7.84 yrs), 34 boys, 34 girls. They were all under control of Outpatient Diabetic Department. Control group were healthy children, age and gender matched. Metabolic control was assessed on the basis of HbA1c level. All children underwent ophthalmology examination, microalbuminuria was evaluated in 24 hours urine samples. VEGF was estimated with use of immunoenzymatic method (RD Systems). RESULTS: In the study group we found: significantly higher levels of VEGF compared to control group (328.68 +/- 251.6 vs 132.19 +/- 85.51 pg/ml: p<0.05). We did not find any differences between genders in VEGF level. VEGF increases with diabetes duration time, and the highest values are in children with diabetes duration over 10 years, although the differences did not reach statistical significance. VEGF level was significantly higher in children with poor metabolic control of the disease (406.65 +/- 322.11 pg/ml vs 132.19 +/- 85.51 pg/ml; p<0.05). Patients with retinopathy had the highest level of VEGF, compared to children without complications. CONCLUSIONS: Assessment of VEGF level can be useful method in prognosis of diabetes microangiopathic complications. As microalbuminuria occurs relatively late in diabetic complications process, evaluation of VEGF may become a prognostic marker of the earliest phases of this complication.