HLA-A gene variation modulates residual function of the pancreatic ß-cells in children with type 1 diabetes.

AIM OF THE STUDY: The study aimed to analyze an association between the HLA-A gene variation and a risk of type 1 diabetes development and to evaluate the association of HLA class I and class II alleles with ß-cell destruction. MATERIAL AND METHODS: A group of 108 children with type 1 diabetes were genotyped in HLA-A, -DRB1, and -DQB1 genes using hybridization with oligonu-cleotides probes. Plasma C-peptide concentration was assessed by radioimmunoassay method. RESULTS: No differences in allele HLA-A distribution between type 1 diabetes patients and healthy individuals were found. Among "low C-peptide"(< 0.28 pmol/ml) individuals, the frequency of HLA-A*02 allele was 41.3%, whereas only one HLA-A*26 allele was detected in this group (0.7%). Conversely, among "high C-peptide"( 0.28 pmol/ml) probands the prevalence of A*02 allele was 19.7% (Pc = 0.008, OR = 1.4, 95% CI: 1.2-1.7) and A*26 10.5 % (Pc < 0.007, OR = 0.15, 95% CI: 0.02-0.9). Genotype analysis showed that A*02/*02 and A*02/X children were more likely to have "low" C-peptide at the onset compared to those with non-A*02/non-A*02 genotype (p = 0.008, OR = 1.6, 95% CI: 1.3-2.0 and p = 0.015, OR = 1.4, 95% CI: 1.1-1.9, respectively). A02 phenotype individuals had lower median C-peptide (0.17 pmol/ml) than non-A02 patients (0.26 pmol/ml, p = 0.008). Median C-peptide was higher in the A26-positive group comparing to A26-negative (0.40 and 0.20, respectively, p = 0.04). No association between HLA class II and C-peptide levels was observed. CONCLUSIONS: HLA-A alleles are not associated with disease development nevertheless strongly influence a residual pancreatic ß-cell function. The results suggest a different role of HLA class I and class II in type 1 diabetes pathogenesis.

Polymorphism of the thymidylate synthase gene and risk of relapse in childhood ALL.

Polymorphisms of genes encoding proteins involved in drug metabolism can influence the efficacy of leukemia treatment. In this population-wide study we aimed to evaluate selected, metabolically active genetic polymorphisms as prognostic markers of treatment efficacy in acute lymphoblastic leukemia (ALL). A total of 51 cases of leukemia relapse were diagnosed in a group of 354 patients with ALL. A strong association between promoter tandem repeat polymorphism of the thymidylate synthase gene and the relapse frequency was found. We believe that genotyping for this variant should be performed in patients treated for ALL to enable further optimizing of treatment protocols.

The cross-reactivity of anti-asparaginase antibodies against different L-asparaginase preparations.

Repeated administration of L-asparaginase leads to the development of specific antibodies and hypersensitivity reactions. The aim of the study was to evaluate a possible cross-reaction of anti-asparaginase antibodies, developed against the native E. coli L-asparaginase (Asparaginase Medac), with other preparations of the enzyme. Sixteen patients with acute lymphoblastic leukemia, in whom in the reinduction phase of treatment hypersensitivity against L-asparaginase was observed and/or the presence of anti-asparaginase antibodies was established were recruited for the present study. Ten out of 16 tested sera showed cross-immunoreactivity to PEG-asparaginase, while no reactivity to L-asparaginase derived from Erwinia chrysantemi was observed. Since cross-reacting antibodies were also found in sera of patients with no overt allergic reaction, L: -asparaginase may undergo silent inactivation during the reinduction phase of therapy. This finding is of clinical importance with regard to appropriate dosage and necessitates careful enzyme activity monitoring in all patients undergoing repeated treatment with various L-asparaginase preparations.

Additional genetic risk factor for death in children with acute lymphoblastic leukemia: a common polymorphism of the MTHFR gene.

BACKGROUND: The presence of metabolically important genetic polymorphisms may affect treatment efficacy in patients with malignancies. The objective of this prospective multicenter study was to evaluate the role of selected polymorphisms of genes associated with metabolism of chemotherapeutic drugs as prognostic markers in children with acute lymphoblastic leukemia. PROCEDURE: Genotyping for the presence of 7 genetic variants in 403 patients and analysis of death cases were performed. RESULTS: Thirty-one children died before reaching remission maintenance phase. Genetic analysis revealed in this group increased frequency of homozygosity for c.677C>T polymorphism of the MTHFR gene (26% vs. 8% in the survivors; OR 4.09; 95% CI 1.67-10; adjusted for multiple testing P = 0.028). CONCLUSION: Our data suggest that modification of anti-leukemic treatment should be considered in patients homozygous for c.677C>T polymorphism.

[Metabolic syndrome in young adults type 1 diabetic patients]. / Zespól metaboliczny u mlodych doroslych chorych na cukrzyce typu 1.

AIM: The aim of the study was to estimate the prevalence of metabolic syndrome (MS) in type 1 diabetic patients and to assess the relationship between the scores of MS components and body mass and metabolic control. MATERIAL AND METHODS: 165 patients aged 18-32 years with diabetes duration 8-26 years were included into the study. The height, weight, waist circumference and blood pressure were measured. HbA1c and plasma lipids concentrations were examined. Body mass index (BMI), waist/hip ratio (WHR) and daily dose of insulin were calculated. MS was diagnosed according to the definition of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) and International Diabetes Federation (IDF). RESULTS: The prevalence of individual components of MS was 10.3% for high triglycerides, 7.3% for low HDL, 27.9% for high blood pressure, and 10.3% for abnormal waist circumference according to NGEP and 18.8% according to IDF definition. After assuming that all type 1 diabetic patients fulfilled criteria for hyperglycemia, the prevalence of MS diagnosed according to NCEP was 10.9% (95% CI 6.1-15.7) and according to IDF was the same 10.9% (95% CI 6.1-15.7). In 14 patients MS was diagnosed according to both definitions, whereas 4 met only the NCEP, and another 4 met only the IDF criteria. Rrelationships between the scores of MS components and BMI (p < 0.0001) and HbA1c (p = 0.002) were found. Patients with MS were older than the patients without MS (p = 0.003) and needed higher insulin doses (p = 0.028). CONCLUSIONS: According to the NCEP and IDF criteria similar prevalence of MS is recognized in type 1 diabetic patients. Only in 2/3 of them MS is diagnosed according to both definitions. The most frequently occurring component of MS is elevated blood pressure. The scores of MS components are related to the presence of overweight and to poor metabolic control.

[Tissue-specific autoimmunity in patients with idiopathic diabetes]. / Analiza tkankowo swoistej odpowiedzi humoralnej u chorych z cukrzyca idiopatyczna typu 1.

INTRODUCTION: According to the WHO classification, type 1 diabetes is divided into type 1A - autoimmune and type 1B - idiopathic. The pathogenesis of the latter remains unknown. Clinical observations confirm that type 1 diabetes is often associated with the presence of other organ-specific autoantibodies. Besides, the idiopathic type 1 diabetes is suggested as resulted form immune-related beta cell destruction with the defect of humoral response. THE AIM: of the study was to verify the above-mentioned hypothesis by an evaluation of the prevalence of thyroid and coeliac antibodies in children with idiopathic diabetes. MATERIAL AND METHODS: The study groups consisted of 37 patients with idiopathic diabetes (group 1B) and 108 patients with autoimmune diabetes (1A). The examined groups were chosen from 569 children with newly diagnosed type 1 diabetes. Anti-islet antibodies (ICA) and antibodies to endomysium were detected by indirect immunofluorescence. Antibodies to tissue transglutaminase were measured by the immunoenzymatic method, whereas the measurement of autoantibodies to insulin, to tyrosine phosphatase and to glutamic acid decarboxylase was determined by radioimmunoassay. RESULTS: Thyroid antibodies were detected in 5.9% of the examined patients from group 1B and 14.7% from group 1A. The frequency of the presence of tissue transglutaminase autoantibodies in both groups was similar (9.4% in 1B and 8.3% in 1A) and in case of endomysial antibodies it was slightly higher in group 1B (9.4% vs 4.8%, p=0.39). CONCLUSION: Since the prevalence of tissue specific autoantibodies is similar in both presentations of type 1 diabetes it is unlikely that a humoral defect of immune response in idiopathic diabetes is observed in this group of patients.

[Idiopathic type 1 diabetes: a heterogenous disease or result of our ignorance?]. / Idiopatyczna postac cukrzycy typu 1: heterogenna jednostka chorobowa czy wynik naszej niewiedzy?

Based on etiology a new classification for diabetes mellitus was proposed by the Experts of WHO in 1999. According to the classification, type 1 diabetes was subclassified as type 1A (autoimmune) and type 1B (idiopathic). Both forms result from the destruction of beta cells, however in type 1A the process is immune-mediated but in type 1B the origin of the beta cells impairment is still unknown. Moreover, subtype B is considered to be very heterogeneous and the diagnostic criteria are still not clear. The purpose of this article was to review studies on the pathogenesis of idiopathic type 1 diabetes.

[The rare syndromic forms of monogenic diabetes in childhood]. / Rzadko wystepujace zespoly cukrzycy monogenowej w wieku rozwojowym.

The most frequent form of diabetes in the childhood is type 1 diabetes. Moreover, the rare forms of diabetes have been also identified in children. Besides of neonatal diabetes caused by the mutations in KCNJ11, SUR1 and GCK genes, other forms of monogenic diabetes are associated with different chronic disorders. These rare forms of syndromic diabetes are related to mutations in genes which lead to Wolfram syndrome, Alström syndrome, Wolcott-Rallison syndrome or Roger's/TRMA syndrome. In this paper we discuss the clinical features of rare syndromic forms of monogenic diabetes, which gave suggestions on pathogenic mechanism of the diagnosed diabetes in childhood. This may be helpful for appropriate classification of the epidemiological, clinical and genetic data. It may be useful in the future to the form of the Polish National Survey of rare syndromic forms of monogenic diabetes in childhood.

Circadian blood pressure variation in normotensive type 2 diabetes patients and angiotensin converting enzyme polymorphism.

BACKGROUND/AIMS: Loss of circadian blood pressure (BP) variation (i.e., lack of nocturnal BP dip by at least 10mmHg, 'non-dipping') is associated with increased mortality rate in subjects with diabetes. We studied whether angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism may play a role in 24-h BP rhythm control. METHODS: The study group was 38 normotensive normoalbuminuric type 2 diabetes patients with impaired BP variation, the controls were 51 well-matched type 2 diabetes subjects with normal 24-h BP rhythm. ACE I/D polymorphism, endothelial function and subclinical inflammation parameters (serum endothelin-1, sE-selectin, intercellular and vascular cell adhesion molecules, tumor necrosis factor-alpha) were assessed. RESULTS: ACE DD genotype was found in 20 (53%), ID genotype in 16 (42%), and II genotype in 2 (5%) study group subjects, while 5 (10%) control subjects had DD genotype, 30 (59%) - ID genotype, and 16 (31%) - II genotype (p<0.0001). Study group subjects presented with marked endothelial dysfunction. CONCLUSION: Impaired circadian blood pressure variation in normotensive normoalbuminuric type 2 diabetes patients is associated with ACE DD genotype and marked endothelial dysfunction when compared to diabetic subjects with normal blood pressure rhythm.

[Acute lymphoblastic leukemia in a child with Sturge-Weber syndrome--case report]. / Ostra bialaczka limfoblastyczna u dziecka chorego na zespól Sturge'a-Webera--opis przypadku.

Sturge-Weber syndrome belongs to the group of neuroektomesodermal diseases, so called facomatoses. In contrast to other diseases of this group, there are not any proofs of the genetic determinated background of the syndrome, as well as the higher frequency of cancer. However, the higher frequency of benign astrocytomas was observed. The presented case of the coincidence of the Sturge-Weber syndrome and acute lymphoblastic leukemia is the second case described in the literature. The authors present the therapeutical problems, associated with glaucoma and epilepsy in the course of this syndrome.

[Insulin glargine improves fasting blood glucose levels in prepubertal children with unsatisfactorily controlled type 1 diabetes]. / Glargina obniza stezenie glukozy na czczo u dzieci z niezadowalajaco wyrównana metabolicznie cukrzyca typu 1.

UNLABELLED: The aim of this prospective cross-over study was to compare glycemic control on NPH insulin (NPH) and on glargine in unsatisfactorily controlled type 1 diabetic prepubertal children. MATERIAL AND METHODS: 14 patients, aged 6-12 years, on multiple insulin injections regimen were included. The study protocol: (i) a 6-month therapy with NPH as basal insulin and (ii) a 6-month therapy with glargine as basal insulin, in a random order. RESULTS: After 4 and 6 months mean blood glucose levels were similar on glargine and on NPH. After 6 months on NPH fasting blood glucose levels were similar to baseline (9.3+/-1.5 and 9.8+/-1.6 mmol/l respectively), while on glargine they were significantly lower compared to baseline (8.0+/-1.4 vs. 9.8+/-1.6 mmol/l, p=0.04) and markedly lower than after 6 months on NPH (8.0+/-1.4 vs. 9.3+/-1.5 mmol/l, p=0.077). HbA1c was lower on glargine compared to NPH, but only after 4 months the difference was statistically significant (7.1+/-0.16 vs. 7.74+/-0.25%, p=0.007). No severe hypoglycemia or ketoacidosis occurred. CONCLUSION: In preadolescent children with unsatisfactorily controlled type 1 diabetes glargine constitutes a useful and safe alternative to NPH, providing better early morning and good total glycemic control, not increasing the risk of severe hypoglycemia; taking it into account the health care systems should participate in its costs for those who can not afford or tolerate an insulin pump.

[Leptin concentration and insulin sensitivity in type 1 diabetic children and adolescents]. / Stezenie leptyny a insulinowrazliwosc u dzieci i mlodziezy chorej na cukrzyce typu 1.

THE AIM OF THE STUDY: was to estimate the relationship between serum leptin levels and insulin sensitivity and components of metabolic syndrome in type 1 diabetic children and adolescents. MATERIALS AND METHODS: 158 patients with type 1 diabetes mellitus (70 girls and 88 boys) aged from 8.2 to 18.4 years (mean: 14.1+/-3.1 years) were included into the study. The diabetes duration ranged from 1.6 to 14.7 years (mean: 3.8+/-2.5 years). The height, weight, waist circumference (WC), skin folds and blood pressure were measured. Body mass index (BMI-SDS), body fat (BF) according to Slaughter formula, and daily dose of insulin were calculated. HbA1c (HPLC method) and serum lipids (enzymatic method) concentrations were examined. Serum leptin concentration was measured by ELISA method. Euglycemic-hyperinsulinemic clamp was performed to estimate insulin resistance. Glucose disposal rate (M index) determined during the last 30 min of the test was calculated as a surrogate of insulin resistance. RESULTS: Serum leptin levels ranged from 1.47 to 57.39 ng/ml (median [quartiles]: 4.60 [3.18-10.2]). M index was 2.10-15.19 mg/kg/min. (median [quartiles]: 7.04 [5.57-8.69]. Leptin was positively correlated with BMI-SDS, WC, skin folds and BF. During puberty leptin levels increased in girls, but in boys the highest levels were observed at Tanner stage 3. Leptin concentrations, normalized for BMI-SDS or BF, were significantly higher in females than in males at Tanner stages 4 (pc=0.047) and 5 (pc<0.001). Leptin was negatively correlated with M index (r=-0.26; p=0.001 adjusted for sex and puberty), but after adjusting for BF or BMI-SDS there were no significant correlations. Leptin was not significantly associated with HDL-cholesterol, SBP and DBP. Using the multivariate linear regression models, we found that plasma leptin remained significantly associated with TG. CONCLUSION: It is likely that the observed relationship between leptin concentration and insulin resistance in young patients with type 1 diabetes is due to body fat composition rather than represents an independent association in this group.

[Prediction of clinical remission using the C-peptide level in type 1 diabetes in children].

UNLABELLED: The aim of the study was to identify individual, clinical and metabolic factors that predict the C-peptide levels and appearance of clinical partial remission during the first year of type 1 diabetes (T1D) in children. MATERIAL AND METHODS: 197 type 1 diabetic patients (84 female and 113 male, mean age 10.4 years) were examined. C-peptide levels were detected by radioimmunoassay at the diagnosis and after 3, 6 and 12 months of the disease. RESULTS: Median C-peptide level at onset was 0.17 pmol/mL (0.11-0.32), peaked in the 3rd month (0.27 pmol/mL, 0.15-0.43; p<0.001) and declined thereafter - 0.21 pmol/mL (0.1-0.34) in the 6th month and 0.13 pmol/mL (0.05-0.26) at the 12th month of the disease. Logistic regression showed that younger age, low pH and higher HbA1c (glycated haemoglobin) at the onset were associated with the "lower" (<0.28 pmol/mL) C-peptide level at the diagnosis. The presence of clinical partial remission was observed in 31% of children. Patients with remission had higher C-peptide levels observed in the first 6 months of T1D than children without clinical remission. Receiver operating characteristic (ROC) curve method was used for the estimation of the threshold of C-peptide level at the onset for the prediction of the clinical remission during the first year of T1D (0.141 pmol/mL, AUC (95%CI) = 0.608 (0.53-0.68)). CONCLUSIONS: Concluding, higher C-peptide level is associated with the appearance of clinical partial remission during the first six months of T1D. C-peptide level may be a good predictor of the clinical partial remission during the first year of T1D.

[Evaluation of the podocytes in urine in the nephrotic syndrome in childhood]. / Ocena podocytów w osadzie moczu u dzieci z zespolem nerczycowym.

UNLABELLED: The pathogenesis of nephrotic syndrome in childhood is still not clear. In most cases minimal change disease, diffuse mesangial proliferation or focal and segmental glomerulosclerosis (FSGS) cause the nephrotic syndrome. To date many studies have revealed that podocytes are the major players in the pathogenesis. The loss of podocytes in urine resulting in podocytopenia is involved in the development of the FSGS. THE AIM OF THE STUDY: We introduced the method of detection of the podocytes in urine and evaluated the podocytes in urine and their association with the clinical course of the idiopathic nephritic syndrome in childhood. We also preliminary estimated this method as a diagnostic tool. MATERIAL AND METHODS: The study group consisted of 50 children with nephrotic syndrome. The podocytes in urine were identified by antibodies against podocalyxin with immunofluorescence method. Statistical analysis looking for correlations between clinical characteristic of nephrotic syndrome and podocyturia was done. RESULTS: Podocyturia was detected in 6 patients. No correlation between clinical characteristic of nephrotic syndrome and podocyturia was found. CONCLUSIONS: Podocyturia is not a constant sign. Podocyturia does not correlate exclusively with FSGS and is present in different histopathological types of glomerulonephritis. Podocyturia does not correlate with proteinuria and clinical characteristics of nephrotic syndrome. Evaluation of the podocyte presence in urine may be a valuable fulfillment of the standard diagnostic methods in glomerulopathies, but its role in the differential diagnosis of glomerulopathies needs further studies.

Parametric clearance kidney scintigrams; diagnostic potential in diabetes.

BACKGROUND: The diagnostic usefulness of parametric clearance kidney images was studied in the early diagnosis of diabetic nephropathy, juxtaposed with conventional dynamic urinary investigation (renoscintigraphy) combined with deconvolution procedure of renal and blood time activity curves and determination of plasma clearance of (99m)Tc-ethylenedicysteine ((99m)Tc-EC). MATERIAL AND METHODS: The investigation was performed on a group of 70 individuals (41 males, 29 females) in whom diabetes type 1 was diagnosed (age 10 to 30 y.; mean 19 y.) and on a control group of 35 healthy individuals (15 males, 20 females) in the age-bracket of 18-25 years (mean 19 y.). In all subjects studied, renoscintigraphy was performed after administration of (99m)Tc-EC (activity 40-120 MBq) combined with determination of urinary clearance (ERPF) of the radiopharmaceutical. The renographic curves were evaluated taking into account their shape and individual share of each kidney, and the clearance function was calculated (RClr). From analysis of the time-activity, kidney curves T(max) and T(1/2) were assessed. In addition, the mean (99m)Tc-EC transport time through the complete kidney (MTT) and organ's parenchyma (PTT) were calculated from results of deconvolution of the curve. From the dynamic urinary system study, conventional images of radiopharmaceutical distribution in the kidneys in the secretion phase were obtained. The parametric clearance images were also computed on the basis of relative clearance values in all the pixels of both kidney regions of interest. The disturbances in kidney function were assessed separately by means of conventional scintigram analysis and of corresponding parametric images. A three-stage classification was used in both cases for the evaluation of abnormal findings in the kidneys RESULTS AND CONCLUSIONS: In all studied individuals, the (99m)Tc-EC (ERPF) clearance values were within the normal range. When renographic time activity curves were considered the flattening of the curves (III phase) was more frequent in diabetic individuals than in the controls (39.3% vs. 15.7%; p = 0.001). The shape of the curves in phases I and II were normal in all studied individuals of both groups. There were no differences observed between mean values of T(max), T(1/2) and PTT in diabetics and controls. However, mean MTT values were significantly higher in diabetics than in controls (p = 0.02). In conventional summation images (phase II of the renograms), there were no significant differences in frequency of defects in kidney parenchyma diabetics and controls (4.3% vs. 2.9%). In contrast, analysis of parametric kidney clearance images revealed that parenchyma defects were found with significantly greater frequency in diabetic individuals (35.7%) than in control subjects (8.6%; p < 0.001). Summarizing the findings, it appears that parametric clearance kidney images reveal local deviations of renal uptake and secretory function while conventional indicators of renal function are still in the normal range. This observation points to the fact that clearance parametric images may have potential value in the early diagnosis of diabetic nephropathy, and perhaps in other types of renal damage. Incorporation of parametric images into the dynamic study of the urinary system may be promising when early detection of kidney damage seems vital.

[Helicobacter pylori infection and its metabolic consequences in children and adolescents with type 1 diabetes mellitus]. / Zakazenie Helicobacter pylori i jego konsekwencje metaboliczne u dzieci i mlodocianych z cukrzyca typu 1.

UNLABELLED: Helicobacter pylori infection (Hp) is the cause of chronic gastritis and duodenitis, ulcer disease, and functional gastrointestinal motor disorders. Its prevalence among Polish children with type 1 diabetes mellitus has been estimated at 25%. There is limited data regarding the influence of Helicobacter pylori infection on clinical course of diabetes, with controversial results. THE AIM: of the study was the estimation of Helicobacter pylori infection on the quality of metabolic control in children and adolescents with type 1 diabetes mellitus. MATERIAL AND METHODS: 198 diabetic patients were investigated (mean age 14.38+/-3.75; range 4.5-25 years), with diabetes duration of 4.91+/-4.21 years (range 0.5-16 years). Screening for Helicobacter pylori infection was performed utilizing the urea breath test (UBTC13); DOB (delta over the baseline) above 3%o was considered positive. Metabolic control included HbA1c (HPLC; Bio-Rad, Munich, Germany) and glucose concentration measurement; glycemia was expressed as area under the curve in fasting and prandial state (AUC). RESULTS: UBT was positive in 48 (24.3%) diabetic patients. HbA1c concentration was significantly higher in patients with Helicobacter pylori infection (7.87+/-1.51 vs. 7.17+/-1.46%; p<0.05). The AUC values were higher in Hp positive diabetic subjects: AUCO 83.75+/-40.99 vs. 66.82+/-31.71 and AUC1 189.86+/-61.57 vs. 149.02+/-51.66 [mg% x 0.5h x 0.5]; p<0.05. CONCLUSIONS: 1. Helicobacter pylori infection significantly worsens metabolic control in children and adolescents with type 1 diabetes mellitus. 2. High prevalence of Helicobacter pylori infection among young diabetic subjects and its influence on glucose control legitimate the screening for Hp inpatients with poor metabolic control of diabetes.

[Post-exercise microalbuminuria in newly diagnosed type 1 diabetic children - preliminary report]. / Mikroalbuminaria powysilkowa u dzieci ze swiezo rozpoznana cukrzyca typu 1 - doniesienie wstepne.

THE AIM: of this study was the evaluation of some factors having an influence on post-exercise albuminuria level in children with newly diagnosed type 1 diabetes as a prognostic factor of developing nephropathy. MATERIAL AND METHODS: 24 newly diagnosed type 1 diabetic children, aged 5.5-16.9 years, mean 10.2+/-3.2, were examined. In order to provoke albuminuria the patients underwent standardized exercise test using treadmill ramp according to the Bruce protocol. Pre- and post-exercise albuminuria and C-peptide levels by radioimmunoassay were evaluated. In urine of patients the albumin / creatinine ratio (ACR) was determined. RESULTS: the tendency towards an increase in ACR ratio in children after exercise (10.5 mg/g (4-27.5) in comparison to the value in pre-exercise urine (7 mg/g (2.5-13), p=0.17) was observed. In 67% of patients (16/24) the ACR ratio was higher in post-exercise urine. In 25% of children (6/24) the ACR ratio was above 30 mg/g which was considered as post-exercise microalbuminuria. Next, parameters of metabolic control of type 1 diabetes were compared between patients with and without post-exercise microalbuminuria. No differences in the serum glucose, HbA1c, BMI, triglycerides, total cholesterol, insulin dose, frequency of ketoacidosis and C-peptide level between these groups of children were noted. CONCLUSIONS: we concluded that the post-exercise microalbuminuria as a marker of diabetic nephropathy risk may be observed in some patients already at the clinical onset of type 1 diabetes but further evaluation is needed to verify this hypothesis.

The anti-asparagines antibodies correlate with L-asparagines activity and may affect clinical outcome of childhood acute lymphoblastic leukemia.

The primary aim of the study was to evaluate the importance of anti-asparaginase antibodies for l-asparaginase activity in children with standard and medium risk acute lymphoblastic leukemia (ALL). Forty-seven children with newly diagnosed ALL were included into the prospective study. Enzyme activity and the presence of anti-asparaginase antibodies (IgG and IgM class) were determined. Anti-asparaginase antibodies were identified in 13/47 (IgM class) and 10/47 (IgG class) patients in the induction and in 19/47 (IgM class) and 20/47 (IgG class) patients in the reinduction phase of treatment. The enzyme activity was lower in patients that were positive for anti-asparaginase antibodies, especially in reinduction phase (median 37 (20 - 180) vs 355 (141 - 499), p = 0.001). An association between anti-asparaginase antibodies and the allergic reaction to the drug was found. Besides, the children who developed anti-asparaginase antibodies in the induction phase of treatment showed lower event-free survival as well as overall survival in comparison with children without antibodies. Since our study was carried out in a small number of patients, this observation is only speculative and needs to be confirmed by a further study on a larger sample size, with multivariable analysis. However, our data suggest that L-asparaginase activity together with anti-asparaginase antibodies measurements may become useful for effective therapy of ALL.