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Copyright of General Practitioner / Lekarz POZ is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Monogenic diabetes are a heterogenic group of diseases with varied phenotypes. It is assumed that they may total up to 10% of all cases of diabetes. Diagnosis of these clinical conditions by an efficient selection of patients for genetic diagnostics may be problematic even for experienced diabetologists. Helpful information about selecting and directing patients for further examinations can be gained from guidelines created by diabetologic societies such as International Society of Pediatric and Adolescent Diabetes (ISPAD). This paper focuses on key aspects of these guidelines and elucidates crucial features of the clinical picture which can be used for differential diagnosis of diabetes. Among factors suggesting monogenic background of diabetes the most notable are: low daily insulin requirement (<0.5 U/kg), moderate hyperglycemia (5.5-8.5 mmol/l), positive familial history with a dominant pattern of inheritance, lack of immunologic markers typical for type I diabetes and presence of structural or functional abnormalities within other organs and systems. ISPAD guidelines however, are burdened by some inconsistencies, reflecting different screening and investigative approaches used by various authors. These incongruities have been resolved by the authors of this paper with added suggestions of how to implement relevant solutions in clinical practice. In this article current guidelines on the treatment of monogenic diabetes in children were also presented. Current therapeutic standards were taken into consideration as well as prospects for treatment of selected forms of monogenic diabetes. It will enable in the near future effective and causal treatment of genetic forms of diabetes in children. [ABSTRACT FROM AUTHOR]

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Recently the prevalence of overweight and obesity in pediatric population - also in type 1 diabetic adolescents - has increased. Aim of the study: Aim of the study was to evaluate prevalence of obesity and central obesity in type 1 diabetic youth. Material and methods: 192 patients (81 girls, 111 boys), aged 10-18 years, with diabetes duration 0.5-15 years were included into the study. The anthropometric parameters were examined. Obesity was recognized according to WHO definition: overweight - BMI 85-95 pc, obesity - BMI >95 pc and according to International Obesity Task Force (IOTF): overweight - BMI >IOTF 25 kg/m2, obesity - BMI >IOTF 30 kg/m2. Central obesity was defined as waist circumference above 90 percentile for sex and age and as waist/height rate (WHtR) >0.5. Local BMI and waist circumference percentiles charts were used. Results: According to WHO criteria overweight was found in 19 girls and 13 boys, obesity properly in 4 and 10, together in 28% and 20.9%. According to IOTF overweight was recognized in 21 girls and boys, obesity properly in 1 and 8, together in 29.3% and 26.4%. According to percentiles charts, central obesity was recognized in 21 girls (25.6%) and in 18 boys (16.4%), together in 20.3% patients. Using WHtR abdominal obesity was found in 7 girls (8.5%) and in 13 boys (11.8%), together in 10.3%. Conclusions: Irrespectively of adopted criteria, overweight/obesity was found in every fourth adolescent with type 1 diabetes. The prevalence of central obesity depends on the adopted criteria. According to local percentiles waist circumference charts, abdominal obesity was recognized twice more frequently than using WHtR. [ABSTRACT FROM AUTHOR]

The aims of the study were: 1. to evaluate the levels of insulin antibodies (IA) during the first 2 years of type 1 diabetes in children and adolescents, 2. to analyze relations between IA and several clinical and metabolic markers. Material and methods: Fifty seven patients (37 males and 20 females) aged 7.6-17.9 years (mean 13.2±2.4) participated in the study. Patients were treated with human insulins and/or with rapid acting human insulin analogs. During the 1st week after diabetes diagnosis, 6 months after diagnosis (N=57) and 24 months after diagnosis (N=42) the following parameters were studied: residual insulin secretion, daily insulin dose, HbA1c, BMI and insulin sensitivity. IA were measured by radioimmunoprecipitation (normal values <7%), C-peptide was measured by radioimmunoassay (the increase in C-peptide concentration 6 minutes after an intravenous injection of glucagon was measured, ΔC-pep). M index measured by euglycemic hyperinsulinemic clamp method by DeFronzo was the measure of insulin sensitivity (higher M index indicates higher insulin sensitivity). Results: Median values (and quartiles) of IA were: 6.7% (5.6-7.4), 16.6% (10.2-37.1) and 17.0% (9.4-38.9) respectively in the 1st week of diabetes and after 6 and 24 months of follow up. IA levels rose significantly during the first 6 months of diabetes (p<0.0001) and remained stable thereafter. After 6 months of diabetes duration the following statistically significant correlations were found: negative between IA and ΔC-pep (r=-0.36, p=0.007), positive between IA and M index (r=0.27, p=0.04) and negative between IA and BMI (ρ?=-0.4, p=0.02); a slight, statistically nonsignificant, correlation between IA and daily insulin dose was noted, too (r=0.19, p=0.16). After 24 months correlation coefficients were as follows: for IA and M index ρ?=0.16, p=0.32, for IA and ΔC-pep ?=-0.08, p=ns, for IA and BMI ρ?=-0.34, p=0.03. Conclusions: 1. Modern insulin preparations induce production of IA in young type 1 diabetic patients. 2. Patients with lower residual insulin secretion require higher daily insulin doses during the first months of diabetes, which may preclude higher IA production. 3. Negative correlation between IA and insulin resistance may be a) secondary to the well known correlation: lower BMI - higher insulin sensitivity or may be due to b) IA acting as a temporary "reservoir" of administered insulin or to c) hypoglycemic activity of IA-insulin complexes. [ABSTRACT FROM AUTHOR]

Introduction: Despite the progress in diagnosis and treatment of type 1 diabetes, diabetic ketoacidosis (DKA) is still a serious clinical problem. The aim of the study was too describe the epidemiology and clinical characteristic of DKA in children and adolescents with type 1 diabetes., Material and Methods: Medical records of 650 patients with type 1 diabetes who were under care of the Outpatient Clinic for Diabetic Children of the Medical University of Lodz from 1st January 2007 till 31 December 2009 were analysed., Results: 101 cases of DKA were reported; the incidence of DKA was 5.2/100 patients /year. Episodes of DKA occurred in 89 patients (39 girls and 50 boys). In 82 patients 1 episode of DKA was recorded, in 3 patients - 2 episodes, in 3 patients - 3 episodes and in 1 patient - 4 episodes. 58.4% (59/101) of DKA episodes occurred in patients with newly diagnosed diabetes (mean age: 8.04-4.78 years) and 41.6% (42/101) - in children with established type 1 diabetes (mean age: 13.3-3.37). DKA was diagnosed in 26,1% of children with new onset of the disease. The most frequent causes of DKA in patients with established type 1 diabetes were noncompliance (22/42) and acute infectious diseases (12/42). Severe DKA was diagnosed in 19/101 episodes, moderate - in 36/101 and mild - in 46/101. No lethal complication of DKA was recorded. The following complications of DKA were observed: dyselectrolitemia (68/101), acute pancreatitis (5/101), gastrorrhagia (1/101), insulin oedema (1/101). Mean duration of hospitalization was 12.03-5.58 days., Conclusions: Newly diagnosed type 1 diabetes is the main cause of DKA in children and adolescents.In established type 1 diabetes the most frequent cause of DKA is poor quality of self-management. Dyselectrolitemia is the most frequent complication of DKA in children. Acute pancreatitis should be considered in a young patient with DKA.

Introduction: A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis., Aim of the Study: The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome., Material and Methods: 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected., Results: In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome., Conclusions: Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

Introduction: The pathogenesis of type 1 diabetes is connected with immune-mediated beta-cell destruction leading to insulin deficiency. The majority of patients will become completely incapable of insulin secretion within a few years, however, some individuals will have persistent beta-cell function years after the diagnosis of diabetes. Despite clinical symptoms of insulin deficiency, residual beta-cell secretion can modify the clinical course and can be an independent factor influencing the delay of development of chronic diabetic complications. The aim of the study was to compare a 10-year clinical course in children with type 1 diabetes with and without preserved beta-cell secretion., Material and Methods: 72 children and adolescents with diabetes lasting for minimum 10 years and available biological material to c-peptide evaluation (3-4 years and 10 years from the onset of diabetes) were chosen from 768 children with type 1 diabetes. We assessed fasting c-peptide and recruited 23 out of 72 patients whose concentration of c-peptide was below or over 0.23 ng/ml at all time points (this cut point derives from the definition of preserved beta-cell function according to DCCT). Afterwards we divided children into two subgroups: A (n=13) - without insulin secretion and B (n=10) - with preserved beta-cell function during 10 years of observation. We assessed markers of beta-cell autoimmunity (ICA, GADA, IA2, IAA) in the examined groups. Insulin requirement and concentration of glycated hemoglobin (assessed as the year mean from four measurements in each year) were compared between group A and B., Results: The age at onset of diabetes in children from both examined groups was similar. All children from group B and 12/13 from group A were positive for at least one type of the screened autoantibodies. There was no difference in insulin requirement between the groups (p=0.6). The level of glycated hemoglobin was significantly lower in group B during a 10-year observational period (p=0.04)., Conclusion: Repeated measures of c-peptide can enable us to define two groups of patients with immune-mediated diabetes with different levels of disease and metabolic control.

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.

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.

Unlabelled: Polymorphism of genes encoding glutathione S-transferases GSTM1, GSTT1 GSTP1 is one of the genetic predictors of susceptibility to cancers in the adults. The frequency of deletions of GSTM1. GSTT1 genes and transition A-G in GSTP1 gene were taken into consideration. THE AIM of this study was to investigate the role of GST genes polymorphisms as a genetic risk factor for acute lymphoblastic leukaemia (ALL), and to study the relationship of these polymorphisms with clinical outcome in childhood leukaemias., Material and Methods: 86 children with newly diagnosed acute leukaemia (female: male ratio = 37:49. median age = 7.8 years) and 460 healthy controls were examined using the PCR and PCR-RFLP methods to identify polymorphisms within GSTM1, GSTT1 and GSTP1 genes. In the group of children with ALL. the frequency of relapses, deaths, clinical course, immunophenotype of blasts and the initial response to prednisone were also analyzed., Results: the higher frequency of A-G transition in the GSTP1 gene was identified in the group of children with ALL in comparison to healthy controls (OR=3.13, 95%CI=1.4-7). We also found that the combination of GSTPl (Val/Val) and GSTM1 null genotypes further increased the risk of ALL (OR= 10.63, 95%CI=3.47 - 32.58; p =0.0001). No differences in the frequency of GSTM1 and GSTTI genes between both groups (OR=1; 95%CI=0,59-1,74 and OR=0, 71; 95%CI=0.45-1.13 respectively) were observed. Statistical analysis has not revealed any connections between polymorphisms within glutathione S-transferases genes and the frequency of relapses and death or poor initial response to prednisone. However, the biphenotypic immunophenotype or B-line blasts were the risk factors of relapse or death of progression in ALL (p=0.03)., Conclusion: transition in exon 5 of GSTP1 gene (alone or combined with GSTM1 deletion) may be one of the molecular predictors of higher susceptibility to acute leukaemia in children. but not of the clinical course of this disease.

Background: C-peptide level is the most reliable factor evaluating the endogenous insulin secretion in patients with type 1 diabetes., Objectives: The aim of the study was to investigate whether the age at onset, gender, presence of autoantibodies and ketoacidosis at diagnosis and insulin requirement, HbA1c levels could be applied to predict the C-peptide levels in the first year of type 1 diabetes in children., Material and Methods: 122 type 1 diabetic children, aged: 2-18 years (average 11.2), 44 female and 78 male were studied. Fasting C-peptide levels were examined by radioimmunoassay at diagnosis, after 10 days and after 1, 2, 3, 6 and 12 months of disease. At diagnosis islet cell antibodies (ICA) were detected by indirect immunofluorescence, antibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase antibodies (IA2A) were measured by microradioimmunoprecipitation assay., Results: Age at onset was positively correlated to C-peptide levels at each evaluated point of the disease (r=0.3-0.46, p<0.0001). One year after diagnosis C-peptide levels decreased in ICA(+) (p<0.04) and GADA(+) (p<0.002) patients but not in ICA(-) or GADA(-) children. There was no significant difference between the IA2A-positive and negative subjects in the C-peptide levels at 12th month of disease. C-peptide level was also related to ketoacidosis at diagnosis, insulin requirement and HbA1c levels during the first year of type 1 diabetes. Logistic regression analysis showed that male, younger age, low pH, higher HbA1c and insulin requirement at onset were associated with decreased C-peptide level at diagnosis (p<0.00002)., Conclusions: Young age, presence of diabetes-related autoantibodies and hyperglycaemia with severe acidosis at the disease onset may be associated with a decreased residual insulin secretion in type 1 diabetes in children.

The aim of this study was to estimate insulin resistance in newly diagnosed type 1 diabetic children and adolescents and to analyse the correlation between insulin secretion and impaired insulin action. 37 patients with type 1 diabetes mellitus aged 12.9 +/- 3 years were included in the study. Duration of diabetes was 6 months. Euglycemic-hyperinsulinemic clamp was performed to estimate insulin resistance. Glucose disposal rate was calculated as index M - mg/kg/min. Insulin secretion was measured by glucagon test. The serum level of cholesterol, HDL-Ch, triglycerides and HbA1 was examined. The height, weight, skinfold, waist and hip circumference were measured. Body mass index and waist/hip ratio were calculated. In children and adolescents with type1 diabetes mellitus insulin resistance of various degree was observed. The glucose disposal rate (M index) was 3.2 - 11.8 mg/kg/min., mean 7.08 +/- 2.5 mg/kg/min. The insulin resistance depended on patients' age (r= - 0.3, p<0.05,) and the stage of puberty. There was no difference in insulin secretion in insulin-resistant and insulin-sensitive subjects. The insulin resistance was related to BMI (r=-0.33; p=0.04), and with skinfold thickness (r=-0.59; p=0.001). In insulin-sensitive children the insulin dose was lower (0.45: 0.67; p<0.02). No influence of insulin resistance on metabolic control was observed. Insulin resistance is observed in newly diagnosed type 1 diabetic children and adolescents. No relationship between insulin secretion and impaired insulin action was found. Insulin resistance was greater during III Tanner stage of puberty and in obese children.

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.

Clinical symptoms of type 1 diabetes are preceded by a long period of prediabetes stage characterised by anti-islet antibodies occurrence as well as insulin and C-peptide secretion disturbances. The aim of this study was to define the prognostic value of type 1 diabetes antiislet humoral markers (ICA, anti-GAD, anti-IA2 and IAA) and to find out thresholds for insulin and C-peptide levels at which clinically overt type 1 diabetes develops. Antiislet antibodies, serum C-peptide and insulin were determined in 86 children who, considering their antiislet autoantibodies levels, were classified as prediabetics (mean value of the observation period: 50 months). 8 (9.3%) children, who after a mean time of 35 months of prediabetes stage developed clinically overt type 1 diabetes, were selected from this group. ICA were determined by indirect immunofluorescence; anti-GAD and IAA by radioimmunoprecipitation. C-peptide and insulin levels were evaluated by radioimmunologic assays (CIS Bio International, France). Kaplan-Meier life table analysis revealed pEFS=0.89 after 92 months' observation. The risk of developing diabetes within 80 months was established. For children with positive ICA the risk rate was 0.21, for ICA and anti-GAD positive individuals - 0.39, and for ICA and IA2 positive - 0.74. A significant difference in insulin and C-peptide levels was found between children who developed clinically overt type 1 diabetes and those in prediabetes stage (9.90 vs. 21.45 micro U/ml, p<0.008; 0.34 vs. 0.67 pM/ml, p<0.001 respectively). For both hormones thresholds for high risk of developing clinically overt diabetes were pointed out. Using ROC method the threshold for insulin was determined at 12.9 micro U/ml, for C-peptide at 0.45 pM/ml. Not only the presence and levels of autoantibodies but also the plasma concentrations of C-peptide and insulin are important prognostics of clinical onset of type 1 diabetes mellitus.

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.