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.

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.

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.

[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.

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.

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.

[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.

[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.

Cytoprotective effect of amifostine in the treatment of childhood neoplastic diseases--a clinical study including the pharmacoeconomic analysis.

Amifostine is an active aminothiol, which has unique properties as a radio- and chemoprotective agent. It has been reported to prevent myelosuppression and reduce the toxic effects of intensive cancer treatment. In the study, 57 courses of chemotherapy in 18 children treated because of neoplastic disease were analyzed to assess the early side effects induced by cytotoxic anticancer therapy. In 18 of them amifostine was used as the cytoprotective agent. The estimation of adverse effects was made in accordance to WHO scale of toxicity, and the pharmacoeconomic analysis was based on the costs of intravenous antibiotics, G-CSF, GM-CSF, blood preparations, immunoglobulins and days of hospitalization. The amifostine use in supportive therapy of neoplastic diseases in children decreases the number of infections thanks to the diminishing of myelotoxic effect. This not only improves the comfort of the patient but also shortens the time of hospitalization. The amifostine therapy limits the costs of treatment, but high price of the drug itself, makes however, the chemotherapy with cytoprotection comparable in pharmacoeconomic analysis to the standard treatment.

[Insulin resistance in type 1 diabetic children and adolescents -- a simplified method of estimation]. / Wskaznik insulinoopornosci u dzieci i mlodziezy chorej na cukrzyce typu 1 -- uproszczony sposób oceny.

BACKGROUND AND AIM OF THE STUDY: Our own studies confirm the hypothesis, that insulin resistance of various degree is often observed in children and adolescents with type 1 diabetes mellitus (T1DM). The knowledge of this parameter characterizing individual patients may be of great value not only for better understanding of the disease course but also as a potential source of specific treatment. Reliable estimation of insulin resistance with hyperinsulinemic euglycemic clamp is a complex, laborious and costly procedure. These facts were enough to motivate us to make an attempt to elaborate an indirect, simplified method of insulin resistance assessment in T1DM children, that would be based on patients characteristics and on clinical parameters of the disease course. MATERIALS AND METHODS: 142 children and adolescents with T1DM (79 boys, 63 girls) aged 7.7-20.3 years (mean age - 13.7+/-3.3 years) were included into the study. Duration of diabetes was 0.5-12.5 years (mean 2.7+/-2.3 years). The stage of puberty was assessed by the Tanner scale. Euglycemic-hyperinsulinemic clamp by de Fronzo was performed to estimate insulin resistance. Glucose disposal rate (M index) determined during the last 30 min of the test estimated insulin resistance. Looking for clinical and metabolic factors characterizing insulin resistance: a) the plasma cholesterol, HDL-Ch, triglycerides and HbA1c were examined, b) the height, weight, waist circumference and blood pressure were measured, c) body mass index and daily dose of insulin were calculated. For statistical analysis the multiple regression was used (forward stepwise method). RESULTS: In the study group M index ranged from 2.1 to 17.4 mg/kg/min (mean 7.27+/-2.62 mg/kg/min). The boys presented better insulin sensitivity than girls (7.79 vs. 6.62, p=0.008). The insulin resistance depended on the patients' age (r=-0.46, p<0.001) and stage of puberty (p<0.001). A correlation between M index and insulin dose (r=-0.34, p<0.05) and HbA1c (r=-0.17; p=0.04) were found. There was a significant relationship between M index and parameters of adiposity, lipids and blood pressure. All significant clinical parameters of insulin resistance were subjected to the analysis. Multiple linear regression analysis was performed. The model with the strongest correlation with index M was used to work out the formula: M index = 17.065 + 1.547 x (gender: boys=1, girls=0) - 0,183 x (age) - 0,117 x (Waist circumference) - 2,019 x (Daily insulin dose) - 0,016 x (LDL-CH) + 0,041 x (DBP). CONCLUSION: In T1DM children and adolescents it is possible to estimate for daily use extent of insulin resistance on the basis of clinical features.

[Prehypertension in type 1 diabetic children and adolescents]. / Stan przednadcisnieniowy u dzieci i mlodziezy chorej na cukrzyce typu 1.

BACKGROUND: The elevated blood pressure is one of the most important risk factors of diabetic micro- and macroangiopathy. AIM OF THE STUDY: Evaluation of the prevalence of prehypertension and relationship between prehypertension, metabolic control and chronic complications in children and adolescents with type 1 diabetes mellitus. MATERIALS AND METHODS: 83 patients aged 12.0-18.9 years, with a duration of diabetes 0.5-17.3 years, without evidence of arterial hypertension were recruited. In all patients 24-hour automatic blood pressure monitoring was performed with oscillometric device. The individuals with >40% of systolic and/or diastolic blood pressure >120/80 mmHg were defined as prehypertensive. HbA(1)c was measured by HPLC, plasma lipid levels--by an enzymatic method and urinary albumin excretion rate by chemiluminescent enzyme immunoassay method. Body mass index (BMI) and daily dose of insulin were calculated. Ophthalmoscopic examination and power spectral analysis of heart rate variation were performed. RESULTS: In 30 individuals (36.1%) prehypertension was diagnosed. The prehypertension group had older age (17.5+/-1.1 vs. 15.9+/-2.3 years; p<0.001) and longer duration of the disease (7.3+/-4.7 vs. 4.7+/-3.4 years; p=0.005) as compared with the group with normal blood pressure. There were no significant differences between groups in HbA1c, daily dose of insulin, BMI-SDS, lipids profile, prevalence of microalbuminuria and retinopathy. In the patients with prehypertension the a greater activity of sympathetic activation was observed (LF/HF: 1.00+/-0.06 vs. 0.78+/-0.04, p=0.018). CONCLUSIONS: Prehypertension is frequently recognized in type 1 diabetic children and adolescents. The prevalence of prehypertension is associated with older age, longer duration of diabetes and the shift of the sympatho-vagal balance toward sympathetic activation. There is no relationship between prehypertension and metabolic control or the prevalence of microvascular complications.

[Polymorphism I/D of the angiotensin-converting enzyme gene and disturbance of blood pressure in type 1 diabetic children and adolescents]. / Zaburzenia cisnienia tetniczego u dzieci i mlodziezy chorej na cukrzyce typu 1 a polimorfizm I/D genu enzymu konwertujacego angiotensyne.

AIM: The aim of the study was to evaluate an association between ACE genotypes and blood pressure (BP) disturbances in children and adolescents withType 1 diabetes mellitus. MATERIALS AND METHODS: 126 normo-albuminuric, type 1 diabetic children and adolescents at the age 10.5-19.7 years, and duration of diabetes 2.0-17.8 years, were included in the study. All patients were clinically normotensive and normoalbuminuric. Twenty-four-hour ambulatory BP monitoring was undertaken in all patients. The values of systolic BP, diastolic BP, mean arterial BP blood pressure and diurnal variation in BP were estimated. Prehypertension was diagnosed as BP values between 90pc or 120/80 mmHg and 95pc. ACE genotypes were assessed using polymerase chain reaction. RESULTS: In 48 individuals (38.1%) prehypertension was diagnosed. ACE genotypes distributed in patients were as follow: 31 (24.6%) genotype II, 45 (35.7%)--ID, and 50 (39.7%)--DD. Patients with DD genotype had higher nocturnal systolic BP (104 vs. 101 mmHg; p=0.029), diastolic BP (54 vs. 52 mmHg, p=0.003) and mean arterial BP (71 vs. 68 mmHg, p=0.003) as compared to carriers of the I allele (group ID + II). In the group DD in compare to the group ID + II lower nocturnal depletion in diastolic BP (18.0 vs. 20.5 mmHg, p=0.024) and mean BP (14.8 vs 16.6 mmHg, p=0.049) was observed. 14% patients of the DD group were non-dipper and 1.32% in the group ID + II (p=0.01). There was no differences in the prevalence of prehypertension between genotype groups (II+ID vs. DD: 38.2 vs. 38.0%, ns). CONCLUSIONS: Genotype DD is associated with nocturnal BP abnormalities in normotensive and normo-albuminuric children and adolescents with type 1 diabetes. There is no relationship between frequency of prehypertension and ACE gene polymorphism.

[Prehypertension risk factors in children and adolescents with type 1 diabetes]. / Czynniki ryzyka stanu przednadcisnieniowego u dzieci i mlodziezy chorej na cukrzyce typu 1.

AIM: Higher blood pressure is a marker of increased risk for development of diabetic angiopathy. The aim of the study was to evaluate the selected factors influencing the prevalence of prehypertension in T1DM children and adolescents. METHODOLOGY: 113 T1DM patients (62 male), aged 12-19 years, with diabetes duration from 0.5 to 17.3 years, without evidence of arterial hypertension during routine examination were recruited. In patients 24-hour automatic blood pressure (BP) monitoring was performed. Prehypertension was diagnosed SBP>120 mmHg and < 95pc and/or DBP>80 mmHg and < 95pc. Among metabolic factors body mass index (BMI), lipids profile, HbA1c and insulin sensitivity index glucose disposal rate (euglycemic hiperinsulinemic clamp) were estimated. As an early marker of autonomic neuropathy heart rate variation was measured. RESULTS: None of the study patients had hypertension. In 35 individuals (31%) prehypertension was diagnosed. The prehypertension group had older age (17.4 vs. 15.8 years, p<0.001), longer duration of disease (6.6 vs. 4.3 years, p=0.003), greater BMI (23.8 vs. 22.0 kg/m2, p=0.01) and lower insulin sensitivity index (5.9 vs. 7.0 mg/kg/min., p=0.04) as compared with the group with normal value of blood pressure. There were no differences between groups in lipids profile and HbA1c. In the patients with prehypertension the greater activity of sympathetic activation was observed (LF/HF--1. 0 vs. 0.82, p=0.02). CONCLUSIONS: Prehypertension is common feature in children and adolescents with type 1 diabetes. The prevalence of prehypertension is associated with older age, longer duration of disease, greater BMI, lower insulin sensitivity and the shift of the sympathovagal balance toward sympathetic activation.

[Polymorphism at the glutathione S-transferase pi locus as a risk factor for ifosfamide nephrotoxicity in children]. / Polimorfizm genu kodujacego transferaze S-glutationowa klasy P1 jako czynnik ryzyka nefrotoksycznego dzialania ifosfamidu u dzieci.

The aim of the study was an assessment of various risk factors for nephrotoxicity of ifosfamide (IF) in children taking into account the importance of the concentrations of toxic metabolites of the drug excreted with urine and the polymorphism of genes encoding S-glutathione transferases of mi, pi, and theta classes (GSTM1, GSTP1 and GSTT1). The study was carried out in 37 children aged 2-17 years (mean age 8.9 +/- 4.5 years) treated with IF in 3 g/m2 dose for various malignant diseases. For the assessment of the incidence of deletion of GSTM1 and GSTT1 genes PCR method was applied while in the case of GSTP1 gene the polymorphism of A-G codon 105 was detected by the PCR-RFLP method. Before and after each treatment cycle the cumulative ifosfamide dose was calculated and the biochemical indices of renal canalicular and glomerular function were assessed which were graduated according to extended WHO criteria. Additionally, nuclear magnetic resonance 31P NMR method was applied for calculation of the concentrations of ifosfamide nephrotoxic metabolites and of the unchanged drug excreted with urine. The analysis performed demonstrated that in children with GSTP1 gene A-G codon 105 transition, a statistically significantly (p = 0.01) higher urinary excretion of toxic ifosfamide metabolites occurred, that increased with the cumulative drug dose. The age, sex and deletions of GSTM1 and GSTT1 genes exerted no effect on the concentrations of the toxic metabolites excreted with urine. The results of the studies demonstrate that GSTP1 gene mutations are the genetic risk factor for nephrotoxic complications of ifosfamide use.

[Urinary tract infections in children under three years of age]. / Zakazenia ukladu moczowego u dzieci do 3 roku zycia.

Urinary tract infection (UTI) in infants and babies is still a challenging problem. The aim of the study was the clinical analysis of children under three years of age with UTI, hospitalised in The Department of Paediatrics, Medical University of Lodz in 2000-2001. The study included 91 children (45 girls and 46 boys), aged 1-36 months; 10 months on the average. Acute UTI was observed in 29% of children, recurrent UTI was diagnosed in 71% of patients. Voiding cystography was performed in 82% of children. Among 28/91 cases of vesicoureteral reflux, 36% were unilateral and 64% were bilateral. Vesicoureteral reflux grade 2 was most frequent (64%) in patients with UTI. The most common pathogen was Escherichia coli. The obtained results demonstrate the necessity of early imaging diagnosis of the urinary system in infants and babies with UTI. Patients under three years of age with UTI require hospitalisation and performance of early diagnostic examinations of the urinary tract.

[Severe hypoglycemia and insulin antibodies levels in children and adolescents with type 1 diabetes]. / Ciezkie hipoglikemie a poziom przeciwcial przeciwinsulinowych u dzieci i mlodziezy chorych na cukrzyce typu 1.

UNLABELLED: Severe hypoglycemia may limit the effects of type 1 diabetes treatment. Insulin antibodies were mentioned to be included in the pathogenesis of hypoglycemia in adult diabetic patients, particularly those treated with non-human insulins. The influence of insulin antibodies on the occurrence of hypoglycemia in children treated with human insulin was not studied. THE AIM of the study was to examine insulin antibodies titers in young type 1 diabetics with a recent history of severe hypoglycemia and in matched control subjects. MATERIALS AND METHODS: Insulin antibodies (IA) were assessed in 33 type 1 diabetic children (mean age 13.2, quartile interval 10.3-16.4) within 14 days after an episode of severe hypoglycemia. In 30 patients from this group, whose serum samples were collected also in the last two years preceding the episode of severe hypoglycemia and stored for routine immunologic assessment, IA levels before severe hypoglycemia were assessed, too. The control group consisted of 30 type 1 diabetic patients (mean age 14.4, quartile interval 12.7-15.4), who never experienced any severe hypoglycemia episode, and matched the study group for sex, age and diabetes duration. All patients were treated either with human insulin or with human insulin analogue lispro and NPH human insulin. Insulin antibodies were determined semi-quantitatively (as serum capacity to bind 125I-insulin) by radioimmunoassay. RESULTS: Compared to controls (median value 19.5%, quartile interval 13.7-30.1%), patients who experienced severe hypoglycemia had higher IA levels after (mean value 30.6%, quartile interval 16.8-39.1%, p<0.04) as well as before hypoglycemia (mean value: 35.9, quartile interval 21.6-46.8%, p<0.02). There was a strong correlation between IA levels measured before and after severe hypoglycemia episodes (r=0.7, p<0.0001) in the study group. CONCLUSIONS: High insulin antibodies levels may be markers of increased risk for severe hypoglycemia acting in a mechanism other than a simple imbalance between exogenous insulin, carbohydrate consumption and physical exercise.

[Factors involved in ketoacidosis at the onset of type 1 diabetes in childhood]. / Czynniki warunkujace wystapienie kwasicy ketonowej w momencie klinicznego rozpoznania cukrzycy typu 1 u dzieci.

BACKGROUND: In some patients the ketoacidosis at the onset of type 1 diabetes has been observed. AIM: The aim of this study was to investigate an effect of the clinical, genetic, immunological and metabolic parameters on the occurrence of ketoacidosis at the clinical onset of the disease. MATERIAL AND METHODS: 106 children with type 1 diabetes, aged 1.8-18.2 years (average 10.6), 40 female and 66 male, were studied. Diabetic ketoacidosis was defined as blood pH of less than 7.35 and severe acidosis as less than 7.2. Among the clinical features, age at onset of the disease and gender of patients were evaluated. Moreover, fasting C-peptide level, insulin requirement, HbA1c level, blood glucose level and body mass index normalized by age and sex were examined at the onset and 6, 12, 24 and 36 months after diagnosis. The HLA-DQA1 and DQB1 alleles and -23 HphI INS polymorphism and CTLA4 gene +49 polymorphism (PCR-RFLP) were studied and islet cell antibodies (ICA) as well as antibodies to glutamic acid decarboxylase (GADA) and thyrosine phosphatase antibodies (IA2A) were also determined. RESULTS: The presence of diabetic ketoacidosis was observed in 55% and severe form in 9% of children. In the group of patients with ketoacidosis lower C-peptide level and lower c-peptide/glycaemia ratio than in children without ketoacidosis were observed (0.20+/-0.18 vs. 0.31+/-0.28 pmol/ml and 0.07+/-0.05 vs. 0.20+/-0.17, p<0.003, respectively). The patients with fasting C-peptide at the onset below normal range (<0.28 pmol/ml) were at high risk of ketoacidosis, OR (95%CI)=3.3 (1.3-8.2). The patients with ketoacidosis were characterized by higher exogenous insulin requirement than non-ketoacidosis individuals (1.2+/-0.6 vs. 0.8+/-0.5 j/kg/24h, p=0.004). Besides, in patients with severe ketoacidosis higher level of IA2A was found as compared to other patients (73.4+/-44.9 vs. 44.2+/-39.6; p=0.04). In this group more frequently 2 and/or 3 different autoantibodies were observed (90% vs. 79%), although, the difference was not significant. CONCLUSIONS: The presence of diabetic ketoacidosis at clinical diagnosis of type 1 diabetes may be related to the residual b cell function, which is mainly determined by the intensity of immunological destruction.

[The influence of systemic blood pressure on renal function in children and adolescents with type 1 diabetes mellitus]. / Wplyw cisnienia tetniczego na funkcje nerek u dzieci i mlodziezy chorych na cukrzyce typu 1.

Elevated systemic blood pressure is one of the most important risk factor of diabetic nephropathy. The aim of the study was to estimate the influence of systemic blood pressure on renal function in children and adolescents with type 1 diabetes mellitus. Fifty-nine patients without evidence of arterial hypertension were recruited. In all patients 24-hour automatic blood pressure monitoring and renal examination (GFR, ERPF, FF, renoscintigraphy, urinary albumin excretion) were performed. The patients were divided into three groups according to blood pressure load: group I (less than 40% of systolic blood pressure--SBP and diastolic blood pressure--DBP values above 90th percentile for sex, age, height and body weight)--26 persons, group II (more than 40% DBP above 90th percentile)--25 persons, group III (more than. 40% SBP and DBP above 90th percentile)--8 persons. The study suggests that 24-hour automatic blood pressure monitoring is useful for early detection of increased blood pressure in diabetic children and adolescents. The patients with elevated both systolic and diastolic blood pressures had more frequently glomerular hyperfiltration. The persons with elevated only diastolic blood pressure had the lowest glomerular filtration and filtration fraction.

[Iatrogenic hyperlipidemia after l-asparaginase and glucocorticoid treatment in two children with acute lymphoblastic leukemia]. / Jatrogenna hiperlipidemia w przebiegu leczenia L-asparaginaza i glikokortykosteroidami u dwojga dzieci z ostra bialaczka limfoblastyczna.

L-asparaginase and glucocorticosteroides are the main drugs used in the first-line treatment in children with acute lymphoblastic leukaemia. One of the observed side effects in the increase of serum level of triglycerides is synergistic manner. The paper describes two children with acute lymphoblastic leukaemia. In these patients we could observe remarkable hypertriglyceridemia, and hypercholesterolaemia with the increase of LDL-cholesterol after applying high doses of L-asparaginase and glucocorticosteroids simultaneously. The above-mentioned disorders were transient. In the analysis of the possible reasons of this pathology we took into consideration family predispositions, the transient deficit of lipoprotein lipase induced by L-asparaginase, improper diet and hyperthyroidismus.