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.

["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.

[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.

Dynamic changes in the trends in incidence of type 1 diabetes in children in Hungary (1978-98).

OBJECTIVE: To determine the recent trends in incidence, to analyze the age and geographic distribution, as well as the seasonal pattern of type 1 diabetes in Hungarian children aged 0-14 yr for the period from 1978 to 1998. METHODS: Primary ascertainment of cases was by retrospective (1978-88) and by prospective (1989-98) registration using hospital notifications. The level of ascertainment was estimated by the capture-recapture method. The temporal trend was estimated by fitting Poisson regression models to the yearly incidence data. Roger's test was used to investigate possible seasonal variation in time of diagnosis. Heterogeneity between geographic areas was assessed by Poisson regression. RESULTS: A total of 2616 patients (1214 in the first 11 yr, 1402 in the remaining 10 yr) were identified; the male:female ratio was 0.93. The overall standardized incidence rate was 7.87 (95% CI = 7.57-8.18) per 100,000 person-yr, the lowest in the youngest (0-4 yr) and highest in the oldest (10-14 yr) age group. There was an increasing trend in incidence with a largest relative annual increase in the youngest age group. Seasonal and regional variations in incidence were also observed. CONCLUSION: Our 21-yr study shows dynamic changes in incidence of childhood type 1 diabetes in Hungary, probably reflecting changes in the environment.