Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

[Anthropometric data, fetal and neonatal complications in infants of diabetic mothers. Results of a 10-year retrospective study]. / Antropometriai jellemzok, foetalis és perinatalis szövodmények diabeteses anyák újszülötteiben. Tízéves retrospektív vizsgálat eredményei.

INTRODUCTION: Disturbances in carbohydrate metabolism during pregnancy may result in harmful fetal and neonatal consequences. OBJECTIVES: To assess the fetal and neonatal complications of pregnancy in mothers with gestational and pregestational diabetes during a 10-year period in a county hospital in Hungary. METHODS: Retrospective analysis of infants of diabetic mothers admitted to the neonatal unit between 2001 and 2010. RESULTS: 32% of the infants were transferred to the neonatal unit. Neonatal macrosomia (birth weight >90 centile) was observed in one quarter of the infants. 39% of the infants developed hypoglycemia (blood glucose <2.6 mmol/l), in the majority of the cases within the first 8 hours. Hypoglycaemia was symptomatic in 55% of the infants. Hypocalcemia was observed in 17%, hyperviscosity in 23%, hyperbilirubinaemia in 32%, respiratory distress syndrome and/or transient tachypnoe in 22% and cardiac complications in 13% of the infants. 10% of the inafnts were affected with birth injuries. Congenital anomalies were seen in 17% of the cases, and severe malformations were present in 4% of the infants. CONCLUSIONS: Despite modern diabetes management, there is still a higher incidence of fetal macrosomia, adverse neonatal outcomes and a higher rate of severe congenital malformations in neonates of diabetic mothers.

Twenty-one years of prospective incidence of childhood type 1 diabetes in Hungary--the rising trend continues (or peaks and highlands?).

The aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 yr in Hungary over the period 1989-2009. Newly diagnosed children with type 1 diabetes aged 0-14 yr in Hungary were prospectively registered from 1989 to 2009. Primary ascertainment of cases was by prospective registration using hospital notifications. Case ascertainment was over 96% complete using the capture-recapture method. Standardized incidence rates were calculated and secular trends estimated using Poisson regression analysis. In Hungary during 1989-2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 [95% confidence interval (CI) 12.1-12.9] per 100,000 person yr. The overall incidence rate has doubled from 7.7 (95% CI 6.4-9.15) per 100,000 per yr in 1989 to 18.2 (95% CI 15.7-20.9) per 100,000 per yr in 2009. A significant linear trend in incidence (p < 0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p < 0.001). The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young. Although it seems that transient periods of stabilization followed by increases in incidence are apparent, the long-term trend continues to be steadily upward. Incidence of childhood type 1 diabetes is a dynamic process, probably reflecting the changes of the environmental exposures and continued registration is necessary to recognize these trends.

[Autoimmune comorbidity and microvascular complications in childhood-onset type 1 diabetes after 20 years of diabetes duration: a questionnaire study]. / Autoimmun komorbiditás és microvascularis szövodmények gyermekkorban diagnosztizált 1-es típusú diabeteses fiatal felnottekben 20 éves betegségtartam után: Kérdoíves vizsgálat.

UNLABELLED: There are no population-based data on the autoimmune morbidity and vascular complications of young adults with childhood-onset type 1 diabetes in Hungary. AIMS: To assess the prevalence of these morbidities after 20 years of diabetes duration. METHOD: Postal questionnaire. RESULTS: 6.2% of the patients had celiac disease. Diabetes was diagnosed at a significantly earlier age in patients with diabetes and celiac disease as compared to those without celiac diasease. Thyroid autoimmunity was reported in 7.6% of cases. They were significantly older with longer duration of diabetes. Every fifth patients reported retinopathy, one sixth of patients was treated for hypertension. Neuropathy was found in 3.4% and kidney disease in 4.8% of the cases. CONCLUSIONS: Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications.

["Constantly rising or peaks and plateaus?" Incidence of childhood type 1 diabetes in Hungary (1989-2009)]. / "Folyamatos emelkedo vagy csúcsok és fennsíkok?" A gyermekkori 1-es típusú diabetes incidenciája Magyarországon (1989-2009).

UNLABELLED: Aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 years in Hungary over the period 1989-2009. METHODS: Newly diagnosed children with type 1 diabetes aged 0-14 years in Hungary were prospectively registered from 1989 to 2009. Standardized incidence rates were calculated and secular trends were estimated using Poisson regression analysis. RESULTS: Between 1989 and 2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 (95%CI 12.1-12.9) per 100 000 person/year. The overall incidence rate has doubled from 7.7 (95%CI 6.4-9.15) per 100 000 per year in 1989 to 18.2 (95%CI 15.7-20.9) per 100 000 per year in 2009. A significant linear trend in incidence (p<0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p<0.001). CONCLUSION: The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young.

Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study.

BACKGROUND: The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be planned. We aimed to establish 15-year incidence trends for childhood type 1 diabetes in European centres, and thereby predict the future burden of childhood diabetes in Europe. METHODS: 20 population-based EURODIAB registers in 17 countries registered 29 311 new cases of type 1 diabetes, diagnosed in children before their 15th birthday during a 15-year period, 1989-2003. Age-specific log linear rates of increase were estimated in five geographical regions, and used in conjunction with published incidence rates and population projections to predict numbers of new cases throughout Europe in 2005, 2010, 2015, and 2020. FINDINGS: Ascertainment was better than 90% in most registers. All but two registers showed significant yearly increases in incidence, ranging from 0.6% to 9.3%. The overall annual increase was 3.9% (95% CI 3.6-4.2), and the increases in the age groups 0-4 years, 5-9 years, and 10-14 years were 5.4% (4.8-6.1), 4.3% (3.8-4.8), and 2.9% (2.5-3.3), respectively. The number of new cases in Europe in 2005 is estimated as 15 000, divided between the 0-4 year, 5-9 year, and 10-14 year age-groups in the ratio 24%, 35%, and 41%, respectively. In 2020, the predicted number of new cases is 24 400, with a doubling in numbers in children younger than 5 years and a more even distribution across age-groups than at present (29%, 37%, and 34%, respectively). Prevalence under age 15 years is predicted to rise from 94 000 in 2005, to 160 000 in 2020. INTERPRETATION: If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70%. Adequate health-care resources to meet these children's needs should be made available. FUNDING: European Community Concerted Action Program.

Type 1 diabetes associated with Hashimoto's thyroiditis and juvenile rheumatoid arthritis: a case report with clinical and genetic investigations.

Autoimmune diseases are initiated by interaction between genetic and environmental factors and caused by the loss of immunologic tolerance to self-antigens. They cluster within families and individuals, but the aggregation in a triad is quite rare. We report a case of a young girl affected by three organ-specific autoimmune disorders, from which type 1 diabetes developed first, then Hashimoto's thyroiditis and juvenile rheumatoid arthritis were diagnosed. Hitherto unreported detailed genetic studies included genotyping of HLA class II, CTLA4, and PTPN22 gene regions. These genes have been associated with autoimmunity in general and some of their variants confer increased risk to all three diseases. Our results - with the limitation of reporting only on a single patient - contribute to the complex genetic background of these clustering organ-specific autoimmune diseases and the analysis of further similar cases might help to reveal how the major and minor genetic factors determine the individual clinical phenotype.

Long-chain polyunsaturated fatty acids in a diabetic teenager during and after nine repeated episodes of diabetic ketoacidosis.

Type 1 diabetes is often accompanied with acute hypoinsulinemia that may theoretically inhibit the conversion of essential fatty acids to their longer-chain metabolites. Previously, we found significant reduction in plasma arachidonic (C20:4n-6) and docosahexaenoic (C22:6n-3) acid values in a group of diabetic children during diabetic ketoacidosis. Here we report data on the changes of fatty acids in plasma phospholipids in a diabetic teenager during and after nine subsequent episodes of diabetic ketoacidosis (DKA). Plasma phospholipid linoleic acid (C18:2n-6) values significantly decreased [23.05 (1.05) versus 19.22 (3.22), % w/w, median (IQR), p < 0.01], while values of dihomo-gamma-linolenic acid (C20:3n-6) and docosatetraenoic acid (C22:4n-6) significantly increased [1.72 (0.44) versus 1.80 (0.63) and 0.40 (0.01) versus 0.45 (0.07), respectively, p < 0.05]. Values of alpha-linolenic acid (C18:3n-3) did not change, while values of docosahexaenoic acid were significantly higher after than during the ketoacidosis [1.57 (0.67) versus 1.87 (0.32), p < 0.05). These data obtained in the same patient during repeated episodes of diabetic ketoacidosis support the concept that hypoinsulinemia plays an important role in disturbances of essential fatty acid metabolism in diabetes.

Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.

AIMS: This article describes the methods, results and limitations of the International Diabetes Federation (IDF) Diabetes Atlas 9th edition estimates of worldwide numbers of cases of type 1 diabetes in children and adolescents. METHODS: Most information in the published literature is in the form of incidence rates derived from registers of newly-diagnosed cases. After systematic review of the published literature and recent conference abstracts, identified studies were quality graded. If no study was available, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Estimates of incident cases were obtained by applying incidence rates to United Nations 2019 population estimates. Estimates of prevalent cases were derived from incidence rates after making allowance for higher mortality rates in less-developed countries. RESULTS: Incidence rates were available for 45% of countries (ranging from 6% in the sub-Saharan Africa region to 77% in the European region). Worldwide annual incidence estimates were 98,200 (128,900) new cases in the under 15 year (under 20 year) age-groups. Corresponding prevalence estimates were 600,900 (1,110,100) existing cases. Compared with estimates in earlier Atlas editions, numbers have increased in most IDF regions, reflecting incidence rate increases, but prevalence estimates have decreased in sub-Saharan Africa because allowance has been made for increased mortality in those with diabetes. CONCLUSIONS: Worldwide estimates of numbers of children and adolescents with type 1 diabetes continue to increase.

Risk of celiac disease in children with type 1 diabetes is modified by positivity for HLA-DQB1*02-DQA1*05 and TNF -308A.

OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH DESIGN AND METHODS: Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis. RESULTS: The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4-0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF -308A.

Lack of association of PAX4 gene with type 1 diabetes in the Finnish and Hungarian populations.

We aimed to assess the possible contribution of the PAX4 transcription factor gene to the genetic background of type 1 diabetes. We analyzed four coding polymorphisms of the PAX4 gene in 498 cases with type 1 diabetes and 825 control subjects from Finland and Hungary. All patients were diagnosed under the age of 15 years according to the World Health Organization criteria. All four PAX4 variants (three in exon 9 and one in exon 3) were genotyped using DNA sequencing. In addition, all Finnish subjects were typed for HLA DR-DQ, insulin gene (-23) HphI, and CTLA4 CT60 polymorphisms. The +1,168 C/A coding variant of PAX4 was found to be polymorphic in both populations (P321H, rs712701). No difference was observed in the genotype frequencies between cases and control subjects, nor was any disease association detected when patients were stratified according to age at diagnosis, sex, HLA, insulin gene, or CTLA4 genotypes. Our data indicate that the +1,168 C/A variant of PAX4 gene does not play any essential role in genetic type 1 diabetes susceptibility. The strong coherence between the datasets of the two ethnic groups studied with highly contrasting disease incidence, socioeconomic characteristics, and profoundly diverse environment emphasizes the impact of this finding.

Prevalence and HLA association of GAD65 antibodies in Hungarian schoolchildren.

Pancreas beta-cell autoantibodies are important tools in prediction of type 1 diabetes, however, background frequencies of these markers reveal considerable population-specific variations. The aim of current study was to determine the frequency of glutamic acid decarboxylase (65kD) antibodies (GADA) in healthy Hungarian schoolchildren (n = 2,664) and to correlate development of GADA with HLA DQ genotypes. GADA was determined using a radioligand assay (cut-off limit: 97.5th percentile); HLA DQ genotypes were identified with allele-specific polymerase chain reaction. Thirty-five children (1.3%) tested positive for GADA among which the proportion of girls was significantly higher when compared with boys (1.8% and 0.8%, p = 0.03). The study population was followed for 5.2 years and one girl in the whole cohort, who tested positive for GADA, has developed diabetes. HLA DQ2/DQ8 and DQ2/y genotypes (where y not equal DQB1*0302, *0301, *0602, *0603) were significantly more prevalent in the GADA positive group than in antibody negative children (17.1% vs 1.7%, p = 0.0003 and 25.7% vs 10.3%, p = 0.027, respectively). In conclusion, the prevalence of GADA in the Hungarian general population is in the middle of the range found in other Caucasian ethnic groups. Individuals carrying HLA DR3-DQ2 haplotype and females were more prone to develop GADA. We suggest that for future screening programs it is important to determine predictive value of islet-cell antibodies in populations with varying disease incidence.

[Predictive genetic screening for type-1 diabetes in the Hungarian population]. / Az 1-es típusú diabetes és a prediktív genetikai szúrés lehetóségei a magyar populációban.

INTRODUCTION: In the modern genetic era the principles of genetic screening are being changed. In addition to diagnostic screening for rare monogenic diseases, predictive screening for common polygenic conditions, like type 1 diabetes, will be more widely implemented. The majority of the genetic background of type 1 diabetes is encoded by the HLA DQ and DR genes, selected variants of which could be used as screening markers. However, risk conferred by various HLA genotypes shows considerable ethnic variation, therefore population-specific screening markers need to be established. AIMS: The aim of this study was to describe a screening strategy based on risk-defining HLA DRB1-DQA1-DQB1 markers to identify individuals at risk for type 1 diabetes in the Hungarian population. METHODS: HLA genotypes of 149 consecutively diagnosed children with type 1 diabetes (age at diagnosis 0-14, mean 8.8 +/- 4.2 years) and 177 randomly selected healthy schoolchildren were studied. Allele-specific polymerase chain reaction method was used for HLA typing. The diagnostic sensitivity, specificity and predictive value of diabetes associated DRB1-DQA1-DQB1 alleles were analysed in a step-wise strategy. RESULTS: The highest diagnostic sensitivity was detected when DQB1 typing was complemented by DQA1 typing on DQB1*0201 positive samples with additional DRB1*04 subtyping in DQB1*0302 carriers. The combination of the following markers gave a relative risk of 28.9 (95% confidence interval: 15.9-52.7, p = 10(-6): DQB1*0201/0302-DQA1*0301,0501-b (b not equal to DRB1* 0403), DQB1*0302/x-DRB1*0401,0402 (not equal to DQB1*0201, 0301,0602,0603), DQB1*0301/0302-DRB1*0401,0404, DQB1*0304/s (s = any DQB1 alleles), DQB1*0201/y-DQA1*0501/a (y not equal to DQB1*0301,0302,0602, 0603,0604, a not equal to DQA1*0201). The diagnostic sensitivity, specificity and positive predictive values for this marker combination were 79.2%, 88.7%, and 1.1%, respectively. CONCLUSIONS: Using HLA DRB1-DQA1-DQB1 markers predictive genetic screening for type 1 diabetes is feasible in the Hungarian population with high diagnostic sensitivity and specificity. At present, such a screening for individuals at risk for type 1 diabetes in the general population is recommended only as part of prospective studies on the natural history or prevention of disease. To increase the positive predictive value of the model, pancreas beta-cell autoantibodies need to be measured and followed in the high-risk cohort.

[Clinical heterogeneity of childhood diabetes in Baranya county]. / A gyermekkori diabetes mellitus klinikai heterogenitása Baranya megyében.

INTRODUCTION: Immune mediated type 1 diabetes is the most frequent form of childhood diabetes while type 2 and other forms are more rare in childhood in the Caucasian population. Differentiation of various diabetes subtypes has importance in the choice of treatment and prognosis. AIMS: The aim of the study was to describe clinical heterogeneity of childhood diabetes and to evaluate possibilities of phenotypical classification. METHODS: Two hundred twenty eight children (128 girls and 100 boys) with diabetes diagnosed at the Department of Pediatrics, University of Pécs, in the period of 1978-2000 were examined. Glycated hemoglobin levels, insulin requirement, body weight at diagnosis and association of type 1 diabetes with other disorders were analysed. RESULTS: Thirty one patients (13.6%) had permanently low (< 8%) glycated hemoglobin levels. Low glycated hemoglobin level associated with low insulin requirement (< 0.5 U/kg/day) was observed in three patients (1.4%) with 4 years of disease duration and in 2 patients (0.9%) during the whole disease course. These patients can be classified as non-classical type 1 diabetes cases. Obesity associated with less than 0.5 U/kg/day insulin requirement observed at least for two years from diagnosis was found in 2 cases (0.9%). These cases may be diagnosed as having childhood type 2 diabetes. The authors identified two diabetes patients with Down syndrome while MODY and transient neonatal diabetes were observed in one cases each. Diabetes associated conditions diagnosed in single cases each were as follows: thymus tumor, Duchenne muscular dystrophy, autoimmune polyglandular syndrome type 2, and T-cell lymphoma. CONCLUSIONS: Childhood diabetes cases can be classified into several subgroups on clinical grounds, insulin requirement, and glycemic control. The data suggest that the prevalence of type 2 and non-classical type 1 diabetes is probably only a few percent among children with diabetes in Hungary. Due to phenotypic overlap between different forms of diabetes, measurement of beta-cell specific autoantibodies and C peptide levels can be recommended for etiologic classification.

[Prevalence and predictive value of GAD65 autoantibodies and their correlation with HLA DR-DQ genotypes in children with type-1 diabetes]. / A GAD65 autoantitest elófordulása, prediktív értéke és összefüggése a HLA genotípussal gyermekkori 1-es típusú diabetesben.

INTRODUCTION: Development of type 1 diabetes is caused by immune mediated destruction of pancreatic beta-cells and is associated with development of islet cell specific antibodies that are molecular markers of the diabetogenic process. Studies on islet cell antibodies will lead to a better understanding of the pathomechanism and improved prediction of the disease. AIMS AND PATIENTS: In present study prevalence of glutamate-decarboxylase (GAD65) antibodies was analysed in a registry based collection of childhood type 1 diabetes cases (n = 122), first degree relatives (n = 164) and ethnically and geographically matched healthy children (n = 2664) in Hungary. Association of GADA with various HLA DQA1-DQB1 genotypes was also studied. METHODS: GADA was determined using a routine radioligand assay and HLA DQA1-DQB1 genotypes were identified with allele-specific polymerase chain reaction method. RESULTS: GADA was more prevalent in children with type 1 diabetes as compared to first degree relatives or the healthy population (71.3%, 95% CI:63.3-79.3 versus 9.1%, 95% CI: 4.7-13.5 and 1.3%, 95% CI: 0.9-1.7; p < 10(-4) and p < 10(-4), respectively). Girls with diabetes were more often positive for GADA than boys (84.1%, 57.6%, p = 0.003) which tendency was seen also among healthy children (1.8%, 0.8%, p = 0.03). Among parents of diabetic children fathers had higher prevalence of GADA than mothers (16.1%, 3.9%, p = 0.03). Diagnostic sensitivity, specificity and positive predictive value of GADA were as follows: 71.3%, 98.7% and 3.7%, respectively. GADA titer was higher in diabetes patients than in first degree relatives or healthy children (62.4 rU +/- 45.8 rU, 23.6 +/- 14.1 rU; p < 10(-4), 17.2 +/- 9.6; p < 10(-4)). GADA was more prevalent among patients with HLA DR3-DQ2 haplotype while it was less prevalent in cases with HLA DR4-DQ8 haplotype as compared to cases not carrying these haplotypes (p < 10(-4) and p = 0.01, respectively). CONCLUSIONS: GAD65 antibodies are specific disease markers for type 1 diabetes. The increased prevalence of GADA among first degree relatives of type 1 diabetes patients indicates an increased risk for development of diabetes in this population. GADA is associated with HLA DR3-DQ2 haplotype and female sex. Positive predictive value of GADA is considerably lower in the general population than in first degree relatives, consequently, for more accurate diabetes prediction the use of additional immune and genetic markers is necessary.

[Decreased first-phase secretion of insulin may play a role in the development of insulin resistance]. / Az inzulinválasz elso fázisának csökkenése szerepet játszhat az inzulinrezisztencia kialakulásában.

Decreased first-phase secretion of insulin may play a role in the development of insulin resistance. In the development of type 2 diabetes an abnormal function of the beta-cells and insulin resistance of liver, fat cells and muscle play the main role. An early sign of beta-cell damage can be the loss of first-phase insulin response. This is supposed to precede the development of insulin resistance. Decrease of first-phase secretion of insulin can induce early postprandial hyperglycaemia and hypertriglyceridaemia damaging endothelium of precapillary arterioles of the nutritive capillaries. Insulin-induced endothelium-dependent dilation of these arterioles is inhibited by high glucose and triglyceride levels preventing metabolic effect of insulin on the parenchymal cells surrounded by nutritive capillaries and leading this way to insulin resistance. Second-phase hyperinsulinaemia develops in the impaired glucose tolerance. With the progression of the disease into the type 2 diabetes, insulin secretion decreases in the second-phase, as well. Because of decrease of first-phase insulin secretion in type 2 diabetic patients, early insulin therapy could be a choice of treatment in type 2 diabetes. Results of the UKPDS suggest that insulin-treated type 2 diabetic patients are longer in the near-euglycaemic state compared to those treated by oral hypoglycaemic agents. Recent data support that early insulin therapy of type 2 diabetic patients retains their own insulin secretion capacity and results in lower haemoglobin A1c. A comparison of before-meal rapid-acting insulin analogue and bedtime NPH insulin regimens verified that rapid-acting insulin analogue decreased haemoglobin A1c compared to NPH insulin treatment in type 2 diabetes. On the basis of these data arises the possibility of the change of the attitude "Oh no, not insulin in type 2 diabetes" to the "early rapid-acting insulin analogue treatment" of these patients.

[Early recognition and successful treatment of an infant with severe combined immune deficiency]. / Súlyos kombinált immundeficiencia korai felismerése és eredményes kezelése.

A male infant of three month presented with recurrent mucosal and fungal infections, diarrhoea and failure to thrive from the age of three weeks. Laboratory test revealed T-B-NK + severe combined immunodeficiency (SCID). Family history and immunolaboratory findings suggested autosomal recessive form of the disease. Haploidentical maternal bone marrow transplantation (BMT) was carried out at five and half months of age. Over the two years after BMT, the patient's somatomotoric and mental development is normal. Cellular immune responses and the substantial immunoglobulin production suggest immunoreconstruction in the child born with complete lack of adaptive immunity. According to the author's knowledge, this is the first T-B-NK + patient in Hungary, whose disease was diagnosed and adequately treated in infancy.

Diabetes in the young - a global view and worldwide estimates of numbers of children with type 1 diabetes.

This paper describes the methodology, results and limitations of the 2013 International Diabetes Federation (IDF) Atlas (6th edition) estimates of the worldwide numbers of prevalent cases of type 1 diabetes in children (<15 years). The majority of relevant information in the published literature is in the form of incidence rates derived from registers of newly diagnosed cases. Studies were graded on quality criteria and, if no information was available in the published literature, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Prevalence rates were then derived from these incidence rates and applied to United Nations 2012 Revision population estimates for 2013 for each country to obtain estimates of the number of prevalent cases. Data availability was highest for the countries in Europe (76%) and lowest for the countries in sub-Saharan Africa (8%). The prevalence estimates indicate that there are almost 500,000 children aged under 15 years with type 1 diabetes worldwide, the largest numbers being in Europe (129,000) and North America (108,700). Countries with the highest estimated numbers of new cases annually were the United States (13,000), India (10,900) and Brazil (5000). Compared with the prevalence estimates made in previous editions of the IDF Diabetes Atlas, the numbers have increased in most of the IDF Regions, often reflecting the incidence rate increases that have been well-documented in many countries. Monogenic diabetes is increasingly being recognised among those with clinical features of type 1 or type 2 diabetes as genetic studies become available, but population-based data on incidence and prevalence show wide variation due to lack of standardisation in the studies. Similarly, studies on type 2 diabetes in childhood suggest increased incidence and prevalence in many countries, especially in Indigenous peoples and ethnic minorities, but detailed population-based studies remain limited.

Interbirth interval is associated with childhood type 1 diabetes risk.

Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years.