Aims/hypothesisThe aim of this study was to study dynamic changes in the prevalence of different types of diabetes in paediatric populations in Poland, with a specific focus on monogenic diabetes (MD).MethodsUsing epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme), we compared the prevalence of type 1, type 2 and cystic fibrosis-related diabetes (CFRD) and MD. Genetically confirmed MD included MODY, neonatal diabetes and Wolfram and Alström syndromes. The study covered all children aged 0–18 years treated for diabetes between 2005 and 2011 in three regions, inhabited by 23.7% (1,989,988) of Polish children, with a low prevalence of childhood obesity (<5%).ResultsThe prevalence of type 1 diabetes showed a continuous increase, from 96 to 138/100,000 children. The prevalence of type 2 diabetes and CFRD also increased, from 0.3 to 1.01/100,000 children and from 0.1 to 0.95/100,000 children, respectively. The prevalence of MD was stable at between 4.2 and 4.6/100,000 children, accounting for 3.1–4.2% of children with diabetes, with glucokinase (GCK)-MODY being the most frequent type, amounting to 83% of patients with MD. The percentage of positive test results decreased with the number of referrals, suggesting that children with the highest probability of MD were referred initially, followed by those with a less clear-cut phenotype. The prevalence of neonatal diabetes equalled 1 in 300,000 children.Conclusions/interpretationThe prevalence of MD in a paediatric population with a low prevalence of obesity remains stable and is nearly fivefold higher than that of type 2 diabetes and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-012-2621-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
The GATA family zinc finger transcription factors GATA4 and GATA6 are known to play important roles in the development of the pancreas. In mice, both Gata4 and Gata6 are required for pancreatic development. In humans, GATA6 haploinsufficiency can cause pancreatic agenesis and heart defects. Congenital heart defects also are common in patients with GATA4 mutations and deletions, but the role of GATA4 in the developing human pancreas is unproven. We report five patients with deletions (n = 4) or mutations of the GATA4 gene who have diabetes and a variable exocrine phenotype. In four cases, diabetes presented in the neonatal period (age at diagnosis 1-7 days). A de novo GATA4 missense mutation (p.N273K) was identified in a patient with complete absence of the pancreas confirmed at postmortem. This mutation affects a highly conserved residue located in the second zinc finger domain of the GATA4 protein. In vitro studies showed reduced DNA binding and transactivational activity of the mutant protein.We show that GATA4 mutations/deletions are a cause of neonatal or childhood-onset diabetes with or without exocrine insufficiency. These results confirm a role for GATA4 in normal development of the human pancreas.
Aims
To present the incidence trend for Type 1 diabetes in Polish children aged 0–14 years, updated using data collected during 2005–2012, and assess the reliability of the predictive model constructed previously using the 1989–2004 database.
Methods
Children aged < 15 years with newly diagnosed Type 1 diabetes are recorded prospectively (EURODIAB criteria) in several regional registers in Poland. Age‐ and gender‐standardized incidence rates for Type 1 diabetes were calculated per 100 000 persons/year. Incidence rates were analysed in terms of the dependency on age, gender, geographical region and population density. Incidence rate trends over time were modelled using generalized linear models.
Results
The mean standardized incidence for 1989–2012 was 12.72 per 100 000 persons/year [95% confidence interval (CI), 11.35 to 14.21]. Over the 24‐year observation period, the incidence increased from 5.36 to 22.74 per 100 000 persons/year. The lowest incidence rate was in children aged 0–4 years (8.35, 95% CI 7.27 to 9.57 per 100 000 persons/year). There was no difference between genders, or urban and rural regions. Incidence rates were higher in northern compared with southern Poland [14.04 (95% CI 12.59 to 15.63) vs. 11.94 (95% CI 10.62 to 13.39) per 100 000 persons/year]. The new data corrected the earlier predictive model by changing the estimates of some factors related to patient age, gender and their interactions with the remaining factors. The incidence rate shows periodic 5.33‐year fluctuations. The periodicity component allows for a more accurate prediction of the incidence rate over time.
Conclusions
This cohort study reveals a sustained increase in Type 1 diabetes incidence in Polish children aged 0–14 years with regular, sinusoidal fluctuations and a slight levelling off in past few years. It is of concern that are the highest increases in incidence are found in children aged 0–4 years.
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