Assessment of preservation of beta-cell function in children with long-standing type 1 diabetes with "ultrasensitive c-peptide" method.

INTRODUCTION: Type 1 diabetes mellitus is a disease caused by the autoimmune destruction of pancreatic beta-cells. It was previously believed that the loss of the endocrine function of the pancreas is total and inevitable. With the rise of new knowledge and new methods allowing to reliably measure c-peptide in the low plasma concentration range, we have learned otherwise. Some residual function of the beta-cells can be present even after decades of the course of the disease. The aim of the study was to evaluate the c-peptide level with routine laboratory and ultrasensitive methods in children with long-standing type 1 diabetes in relation to clinical characteristics. METHODS: We recruited 178 consecutive children with type 1 diabetes mellitus lasting at least 1 year, mean diabetes duration was 5.6 years. Basic anthropometric measurements were performed and blood samples were drawn. From patients history records we gathered data regarding the course of the disease and laboratory results previously acquired. Laboratory tests performed on the blood samples included HbA1c levels and c-peptide level measurement using classic (n=178) and ultrasensitive (n=160) method (Mercodia). Clinically relevant c-peptide level was set at 0.23 ng/ml according to the DCCT recommendations. RESULTS: Clinically relevant c-peptide was found in 54 of 160 (33.75%) patients. Patients with preserved c-peptide were older at the time of diagnosis, had longer clinical remission, and required lower total and basal doses of insulin. Significantly lower mean HbA1c from the last year, but higher HbA1c at the time of the diabetes diagnosis were found in the group with higher c-peptide levels. The comparison of the classic and ultrasensitive c-peptide tests revealed that both yield similar results. CONCLUSIONS: Our observation shows that 34% of young patients with long-standing type 1 diabetes have prolonged c-peptide secretion. We confirm the long-standing assumption that residual beta-cell function is beneficial for metabolic control of the patients. Classic method of the c-peptide measurement can be just as useful in clinical practice as the ultrasensitive one.

[Prevalence of autoimmune diseases and microangiopathy in children with diabetes type 1 over the years 2000-2010]. / Wystepowanie chorób autoimmunizacyjnych oraz mikroangiopatii u dzieci z cukrzyca typu 1 w latach 2000-2010.

INTRODUCTION: In the past decade the number of patients with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) has increased rapidly. Treatment of the disease is focused on proper physical development and the prevention of complications. Aim of the study was to analyze changes in the treatment and clinical picture of type 1 diabetes in children over the years 2000 to 2010 with particular emphasis on the presence of autoimmune diseases and microangiopathy. MATERIAL AND METHODS: The study included 567 children diagnosed with type 1 diabetes under the care of outpatient diabetes clinic. We compared 251 children, diabetes outpatient clinic patients in 2000, with 316 children in 2010. Data were obtained from the outpatient and hospital records. We compared baseline demographic, anthropometric data, treatment regimen, type of insulin, metabolic control, prevalence of autoimmune diseases and microangipathy. RESULTS: In 2010 there was a reduction in the age of diagnosis of diabetes from 10 to 8 years (p=0.039). Significantly increased the proportion of children treated with CSII (up to 60.1%) and decreased the percentage of children using conventional insulin for the benefit of insulin analogs. The increase in HbA1c from 7.4 to 8.0% (p<0.001) has been shown and increase in proportion of patients with HbA1c >7.5% in 2010. The percentage of children with obesity increased from 5.2 to 13.7% (p=0.004) and there was a significant increase in SDS-BMI. The percentage of children with autoimmune diseases such as celiac (from 0,4 to 7,3%, p<0,001) and thyroid (from 6.9 to 21.3%, p<0.001) has increased. The incidence of retinopathy decreased from 6 to 1% (p=0.04), and albuminuria decreased insignificantly. CONCLUSIONS: Over the last decade, a significant change in the method of treatment in children diagnosed with type 1 diabetes has occurred. The deterioration of metabolic control, despite the frequent use in the treatment of CSII, may be due to increased frequency of obesity and additional autoimmune diseases in today´s patients. More similar to physiologic way of insulin infusion in nowadays treatment may influence the decrease in the prevalence of retinopathy.

[Quality of treatment in children with type 1 diabetes based on the Polish Prospective Pump Programme]. / Jakosc leczenia dzieci z cukrzyca typu 1 w oparciu o ogolnopolski prospektywny program leczenia przy uzyciu pomp insulinowych.

BACKGROUND: In pediatric patients with type 1 diabetes mellitus, the value of HbA1c is a predictor of the risk of late systemic complications in adulthood. In the last years significant changes in the method of treatment in pre-pubertal children with T1DM have taken place. However, there is lack of precise data concerning the results of metabolic control of this group of patients. THE AIM: was to assess the impact of the Polish Prospective Insulin Pump Programme (OPPLP) on the quality of metabolic control in prepubertal children with T1DM. The OPPLP included also education for diabetological staff (HPC) from the Polish Diabetic Centres as well as standardization of continuous subcutaneous insulin infusion (CSII) implementation procedures. MATERIAL AND METHODS: Population studies were conducted in the years: 2005-2008. 920 patients were enrolled at age from 1.2 to 14.6 years (median 8.5 years). 71.75 % of patients were in pre-pubertal age. 734 patients received CSII therapy. The cross sectional, prospective study, conducted according to the protocol of the OPPLP with clinical data collection from 2005 to 2008. We analyzed the data obtained during 1657 visits and assessed 1657 blood samples for HbA1c value in the Central Laboratory. The clinical data were recorded in the electronic net-database. RESULTS: In whole group the median of HbA1c was 7.46 % (min. 5% - max. 12.1%); 60.1% patients has HbA1c below 7.5%. The quality of treatment was comparable among the centres: med. HbA1c ranged from min. 6.5% to max. 8.0%. During the period from 2005 to 2008 effective results were obtained in glycemic control: med. HbA1c: 2005 - 7.6%, 2006 - 7.2%, 2007 - 7.0% and 2008 - 7.5%. Slightly higher HbA1c was observed in children with longer duration of diabetes (r=0.17, p<0.005). CONCLUSIONS: The OPPLP, including HCP education, enabled optimalization of metabolic control in the prepubertal children switched pump therapy. Moreover, the programme brought about an even level of treatment between the Polish Diabetic Centres irrespective of their size. It is important to continue the programme and to develop a country level register of children with T1DM.

[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.

[Asymmetric dimethylarginine (ADMA) in children with diabetes type 1]. / Asymetryczna dimetyloarginina (ADMA) u dzieci z cukrzyca typu 1.

INTRODUCTION: Asymmetric dimethylarginine (ADMA), a naturally occurring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA is now recognized as an independent marker of endothelial dysfunction and atherosclerosis. Data concerning ADMA level in type 1 diabetes (DM1) are controversial. The aim of the study was to evaluate ADMA level in children with DM1, without clinical evidence of vascular complications, with particular attention to additional cardiovascular risk factors (hypertension, obesity, hyperlipidemia). MATERIAL AND METHODS: The study group included 72 children with DM1, aged mean 15±3 yrs (8-20 yrs), 33 boys and 39 girls, with diabetes duration time mean 6.6±3.5 yrs (1-14 yrs), HBA1c mean level 8.2±2.3% (5.6-15%). The control group consisted of 41 (19 boys and 22 girls) healthy children, aged mean--14.8±2.6 yrs, from 8 to 18 yrs, gender matched, with no family history of cardiovascular disease. ADMA level was determined in plasma using ELISA kit (DLD Diagnostica, Hamburg, Germany) RESULTS: ADMA level was similar in children with diabetes and in the control group: 0.69±0.33 vs. 0.7±0.27 µmol/L, ns. We did not find differences in ADMA level in diabetic children with the presence of additional diseases being cardiovascular risk factors. In the group of 13 children with hypertension ADMA level was the highest: 0.79±0.25 µmol/L, but the difference was statistically insignificant in comparison to children with diabetes without hypertension and in comparison to healthy controls. CONCLUSIONS: Children with DM1, without clinically evident vascular complications, have ADMA levels similar to healthy children. A possible relationship between ADMA and hypertension in these patients requires further investigation.

[Higher percentages of T regulatory cells in children at risk for developing type 1 diabetes mellitus]. / Podwyzszone odsetki limfocytów T regulatorowych u dzieci z grupy ryzyka zachorowania na cukrzyce typu 1.

INTRODUCTION: The natural history of type 1 diabetes is concerned with the appearance of autoantibodies against antigens of pancreatic beta cells. The last decade revealed some evidence of the participation of T regulatory lymphocytes - cells which suppress immune response - in the pathogenesis of type 1 diabetes and prediabetes. AIM OF THE STUDY: was the assessment of T regulatory cells in the blood of children at risk for developing type 1 the diabetes mellitus. MATERIAL AND METHODS: 85 subjects, siblings of children with type 1 diabetes, were enrolled into the study. The presence of anti-GAD65 antibodies was assessed. With the use of flow cytometry the following cell subpopulations were noted: CD4+, CD4+CD25high and CD4+CD25highCD127low with the coexpression of: CD28, CD45RO, CD54, CD62L and CD134 molecules. RESULTS: We did not observe any differences in white blood cell count, lymphocyte (including CD4+) count and the percentage between the examined and control groups. We noted higher percentages of T regulatory cells: CD4+CD25high, CD4+CD127low and CD4+CD25highCD127low in children with the presence of anti-GAD65 antibodies as compared to the control children. CONCLUSION: Higher percentages of T regulatory cells in the blood of children with the presence of anti-GAD65 antibodies may suggest an intensive regulatory response present in patients at risk for developing type 1 diabetes.

Lower percentages of T regulatory cells in children with type 1 diabetes - preliminary report.

INTRODUCTION: Type 1 diabetes (T1D) isa well-known autoimmune disease, however there are still some processes in its pathogenesis to be elucidated. In the last few years the role of T regulatory cells in the pathogenesis of T1D has been investigated. The aim of study was to determine the percentages and numbers of T regulatory cells in the peripheral blood of children with type 1 diabetes. MATERIAL AND METHODS: A total of 25 children with newly diagnosed type 1 diabetes were studied, and compared to the control group consisted of 30 healthy children with no signs of autoimmune, chronic, inflammatory, neoplastic disease, and no evidence of T1D in their families. Flow cytometric analysis ofT-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, and anti-CD127 (IL-7R). RESULTS: In the group of children with type 1 diabetes we noted statistically significant lower percentages of T regulatory cells, i.e., CD4+CD25 high and CD4+CD127 low comparing to the control children. There were no differences in other assessed parameters: white blood cell count, lymphocytes, CD4+ and CD4+CD25 high CD127 low cells (percentage and count). We did not find the correlation between patients' age and any of analysed parameters. CONCLUSIONS: Our results suggest the lower percentages of Tregs in children with T1D, however those data need to be confirmed in a larger cohort of patients and complemented with functional studies, e.g. at mRNA level. In our opinion T regulatory cells could be excellent candidates for cell therapy in newly diagnosed type 1 diabetic children.

[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.

[Selected matrix metalloproteinases (MMP-2, MMP-9) in obese children and adolescents]. / Ocena stezenia wybranych metaloproteinaz macierzy zewnatrzkomórkowej (MMP-2, MMP-9) u dzieci i mlodziezy z otyloscia prosta.

INTRODUCTION: In the last years it has been proved that matrix metalloproteinases participate in the development of all stages of atherosclerotic process. It has been suggested that plasma levels of metalloproteinases can be a novel, inflammatory marker of atherosclerosis. THE AIM OF THE STUDY was to evaluate plasma levels of selected matrix metalloproteinases (MMP-2 and MMP-9) in obese children and adolescents. MATERIAL AND METHODS: We studied 45 children and adolescents with simple obesity aged 15+/-1.8 years. The control group comprised 28 healthy, slim children aged 14.5 years. The obese children were studied according to coexistence of hypertension, hyperlipidemia, positive family history of cardiovascular diseases and insulin resistance. Levels of matrix metalloproteinases were assessed by use of ready ELISA kits (R&D Systems). RESULTS: MMP-9 level in the study group equaled 553.5+/-311 ng/ml and was significantly higher compared to the control group: 400.4+/-204 ng/ml, p=0.02. MMP-2 level in the study group was significantly lower compared to the control group: 211+/-37 ng/ml vs. 258+/-56 ng/ml, p<0,0001. In obese children with coexisting hypertension we found higher levels of MMP-9 when compared to children with obesity only: 635+/-308 ng/ml vs. 450+/-289 ng/ml (p=0,04), MMP-2 levels remained similar in both groups. CONCLUSIONS: Different levels of plasma matrix metalloproteinases in obese and hypertensive children compared to healthy, slim controls can indicate an altered metabolism of the extracellular matrix (ECM) of vessels and heart muscle. Changed metabolism of ECM may be of significant importance in enhancing the atherosclerotic process in this young 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.

[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.

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.

[How often does decreased consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1 and what are its consequences?]. / Jak czesto wystepuje zmniejszona swiadomosc odczuwania hipoglikemii u dzieci i mlodziezy z cukrzyca typu 1 i jakie sa tego nastepstwa?

UNLABELLED: The inability of the patient to recognize the risk of hypoglycemia is a very frequent phenomenon, but it is also often an underestimated complication in diabetes treated with insulin. The results of DCCT trial revealed that intensification in insulin therapy increases three-fold the risk of severe hypoglycaemia. Feeling the state of hypoglycaemia is the basic defensive mechanism in patients with diabetes type 1, making possible to start the self treatment. The decreased consciousness of hypoglycaemia makes limitations to intensive insulin therapy, which main aim is to stop later complications. THE AIM OF THE STUDY was to answer the questions: 1. How often does lack of consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1. 2. What are the possible factors influencing appearance of hypoglycaemia. 3. Is lack of hypoglycaemia consciousness of a risk factor for severe hypoglycaemia. MATERIAL AND METHODS: The study was carried out on 318 patients aged x=13.6 yrs (4-21), suffering from diabetes, mean 6.6 yrs (2-18). The study was retrospective taking into consideration the period from 1.01.1998 to 31.12.2002. RESULTS: In the analysis of the questionnaire assessing the occurrence of hypoglycaemia it was found that 82 patients (25.8%) have problems with feeling the state of hypoglycaemia. We analyzed the influence of time of lasting diabetes and we found that patients with a longer duration of the disease more frequently have problems with feeling hypoglycaemia, 57% patients with lack of hypoglycaemia consciousness have bad metabolic control of the disease. In the analyzed period, 64 incidences of severe hypoglycaemia in 48 patients (30 boys and 18 girls) were found. In patients with lack of consciousness of feeling hypoglycaemia the incidences of severe hypoglycaemia occurred ten times more frequently compared to patients who feel hypoglycaemia. Sleeping makes it impossible to perceive early symptoms of hypoglycaemia: in our patients 51 severe incidences (79.7%) occurred at 1.00-3.00 a.m., 6 (9.3%) occurred at daybreak and 7 (11%) in the evening. CONCLUSIONS: 1. In patients with diabetes type 1 the lack of hypoglycaemia consciousness occurs in about 25%. 2. The lack of hypoglycaemia consciousness is closely connected with time of diabetes duration and with recurrence of hypoglycaemia incidences. 3. Patients with lack of hypoglycaemia consciousness are at greater risk for severe hypoglycemia.

[Prevalence of chronic diabetes complications depending on the method of insulin therapy in children and adolescents with type 1 diabetes]. / Wystepowanie powiklan przewleklych w cukrzycy typu 1 u dzieci i mlodziezy w zaleznosci od metody insulinoterapii.

UNLABELLED: The critical study showing advantages of intensive insulin therapy in comparison with the classic method was Diabetes Control and Complications Trial. Conclusion of that study was unequivocal: hyperglycemia has a significant influence on the development of the chronic diabetes complications. THE AIM of this study was to estimate the influence of the conventional insulin therapy in the past and its duration on the development of complications in patients suffering from type 1 diabetes for more than 5 years. MATERIAL AND METHODS: 185 patients aged 16.7 years (+/-3.4) with diabetes onset in the age 8.4 years (+/-3.8) participated in this study. There were 84 girls and 101 boys. More of them were treated by classic insulin therapy at the beginning of disease (n=148). 37 persons had intensive insulin therapy all the time. RESULTS: The presence of at least one complication was found in 49 persons (26.5%), two complications - in 14 patients (7.57%) and three complications in 4 patients (2.16%). The conventional therapy duration was twice longer in patients with retinopathy. The significant influence of the age, the age of diabetes onset and duration was found in those patients. Comparing the groups of patients treated conventionally less than 3.5 years and more than 3.5 years it was found that patients in the first group were older, fell ill later and they had longer diabetes duration than patients in the second group. The risk of retinopathy increases from 4.2% to 8.9% in patients treated conventionally more than 3.5 years. The risk of diabetic cataract is 5 times higher in that group. CONCLUSIONS: Chronic complications of diabetes occur in 26.5 % patients with a diabetes duration of at least 5 years. CIT is the risk factor of the eye complications in diabetes, particularly when applied longer than 3.5 years. The prolongation of CIT over 3.5 years increases the risk of retinopathy twice and the risk of cataract 5 times in patients with type 1 diabetes. So the early intensification of insulin therapy reduces the risk of the retinopathy and cataract development in later course of the disease.

[Assessment of growth factor levels in adolescents with type 1 diabetes mellitus and the beginning of diabetic microangiopathy]. / Ocena poziomu czynników wzrostowych u mlodziezy z cukrzyca typu 1 i rozpoczynajaca sie angiopatia cukrzycowa.

OBJECTIVE: The purpose of the study was the evaluation of growth hormone (GH), insulin-like growth factor (IGF-1), insulin-like growth factor binding protein (IGFBP-3) and vascular endothelial growth factor (VEGF) in adolescents with type 1 diabetes as well as the relationship between the concentration of examined proteins and the early development of diabetic microangiopathy. RESEARCH DESIGN AND METHODS: The study included 68 patients aged 15.54+/-2.9 years with type 1 diabetes. They were divided into groups: I - adolescents with the beginning of vascular complications, II - without complications. Controls consisted of healthy adolescents. GH, IGF-1, IGFBP-3 and VEGF were determined with use of ready kits. RESULTS: The increased levels of GH were found in diabetic adolescents in comparison with controls (10.11+/-16.21 vs. 2.89+/-4.03 micro IU/ml, p<0.05). The levels of IGF 1 were lower in adolescents with type 1 diabetes than in controls (283.48+/-117.36 vs. 427.95+/-177.48 ng/ml, p<0.05), as well as the levels of IGFBP-3 (5555.21+/-1158 vs. 6622.18+/-1110 pg/ml, p<0.05). Significantly higher concentration of VEGF was revealed in diabetic adolescents in comparison with controls (328.68+/-251 vs. 132.19+/-85 pg/ml, p<0.05). The highest levels of VEGF were reported in diabetic patients with retinopathy in comparison with patients without complications. CONCLUSIONS: The impaired activity of GH-IGF-1-IGFBP-3 axis may be responsible for the development of diabetic microangiopathy. The evaluation of VEGF concentration can be a sensitive early marker of microangiopathy.

[Selectins in the pathogenesis and diagnosis of early atherosclerotic changes in children and adolescents with risk factors (obesity, hypertension and diabetes)]. / Udzial selektyn w patogenezie i diagnostyce wczesnych zmian miazdzycowych u dzieci i mlodziezy z czynnikami ryzyka (otyloscia, nadcisnieniem, cukrzyca).

UNLABELLED: Selectins are the group of adhesion molecules, which main role is the tethering of leukocytes to the endothelium. They induce relatively weak and transient adhesion allowing the cells to roll along the vascular wall. That mean, that selectins play part in the earliest stages of the atherosclerotic process. The aim of the study was to evaluate levels of E-selectin, L-selectin and P-selectin in children and adolescents with traditional atherosclerosis risk factors (obesity, hypertension and diabetes), correlation with lipid parameters, blood pressure values and BMI as well as the attempt to answer the question whether selectins, and which of them can be useful in predicting cardiovascular risk in these young patients. MATERIAL AND METHODS: We studied 66 children aged 14.8+/-2.6 years. They were divided into 4 subgroups according to the diagnosis: children with obesity--OP (n=12), children with obesity with hypertension--OP and NT (n=14), children with hypertension--NT (n=12), children with diabetes--C (n=28). Control group consisted of 15 healthy, slim children and adolescents, aged 15.4+/-2.2 yrs. Levels of E-selectin, P-selectin and L-selectin were evaluated by immunoenzymatic methods with use of R&D Systems ELISA kits. RESULTS: In the study group we found significantly higher level of E-selectin--86+/-28 ng/mL compared to control group: 64+/-20 ng/mL (p<0.05). Similarly in all subgroups levels of E-selectin were significantly higher: in obese children E-selectin level was 95+/-31 ng/mL (p<0.05), in obese and hypertensive group--88+/-12 ng/mL (p<0.05), in hypertensive group--79+/-19 (p<0.05), and in diabetic children--83+/-25 ng/mL (p<0.05). L-selectin level in the study group was 1552+/-290 ng/mL and did not differ from control group--1652+/-281 ng/mL (ns). P-selectin level in the study group was 652+/-419 ng/mL and was similar to the level of P-selectin in the control group--669+/-295 ng/mL (ns). Correlation analysis showed significant relationship between E-selectin and BMI (r=0.23, p<0.05) and diastolic blood pressure (r=0.24, p<0.05). CONCLUSIONS: 1. Young patients with atherosclerosis risk factors have elevated level of E-selectin. 2. E-selectin level correlates with BMI and diastolic blood pressure. 3. Elevated level of E-selectin may confirm endothelial dysfunction in young patients with atherosclerosis risk factors and can serve as a marker of early atherosclerosis phases.