Grażyna Deja

Transition from pediatric to adult diabetes care: smooth or slippery?

de Beaufort C, Jarosz‐Chobot P, Frank M, Frank M, de Bart J, Deja G. Transition from pediatric to adult diabetes care: smooth or slippery?

GATA4 mutations are a cause of neonatal and childhood-onset diabetes

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.

Epidemiology of type 1 diabetes among Silesian children aged 0–14 years, 1989–2005

The aim of this study was to estimate the present Polish incidence rate of diabetes mellitus type 1 in children aged 0–14. The research was conducted between 1989 and 2005 among the children of Upper Silesia region (Poland), being the part of the EURODIAB program, according to all criteria of this project. During this period, 1,385 new cases (720 boys) of diabetes mellitus type 1 were recognized. The analysis of the standardized incidence rates performed after dividing into shorter periods (1989–1994, 1995–1999, 2000–2005) showed a sharp increase from 5.80/105/year through 9.54/105/year to 15.26/105/year, respectively, in the periods. Analysis of age subgroups showed the greatest increase in the incidence rate among the younger children: 3.59 times for children aged 0–4, 3.40 times for children aged 5–9 and 2.08 times for children aged 10–14. No significant difference of incidence rate between boys and girls was established. Such high increase of incidence rate of diabetes mellitus type 1 (above 260%) noted since 1989 shows a secular trend of an epidemic of diabetes mellitus type 1 in Poland and a conversion from countries with the lower incidence rates in Europe to the countries with the highest incidence rates.

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK‐MODY from HNF1A‐MODY and type 1 diabetes in children and young adults

Introduction  Confirmation of monogenic diabetes caused by glucokinase mutations (GCK‐MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK‐MODY is most prevalent.

Is the Association Between TNF-α-308 A Allele and DMT1 Independent of HLA-DRB1, DQB1 Alleles?

The aim of the study was to assess chosen factors of genetic susceptibility to DMT1: DRB1, DQB1, and TNF-α polymorphisms-308 (G/A) in children with DMT1 and their up-to-now healthy siblings. Then we tested whether the association between TNF-α genes and DMT1 is independent of HLA. 87 diabetic children, their 78 siblings, and 85 persons from healthy control group were followed up. The highest risk of DMT1 was connected with alleles: DRB1*0401 (OR = 3.39; CI: 1.55–7.41), DRB1*0301 (OR = 2.72; CI: 1.48–5.01), DQB1*0201 (OR = 4.04; CI: 2.17–7.52), DQB1*0302 (OR = 5.08; CI: 2.54–10.14), and TNF-α-308 A allele (OR = 2.59; CI: 1.23–5.44). Moreover linkage disequilibrium for TNF-α-308 A allele with DRB1*0301 and DQB1*0201 was observed in both diabetic children and their siblings. Diabetic children and their siblings present similar genetic risk factors for DMT1. The association between TNF-α-308 A allele and DMT1 is dependent of HLA-DRB1 and DQB1 alleles.

Novel glucokinase mutations in patients with monogenic diabetes - clinical outline of GCK-MD and potential for founder effect in Slavic population.

Borowiec M, Antosik K, Fendler W, Deja G, Jarosz‐Chobot P, Mysliwiec M, Zmyslowska A, Malecki M, Szadkowska A, Mlynarski W. Novel glucokinase mutations in patients with monogenic diabetes – clinical outline of GCK‐MD and potential for founder effect in Slavic population.

Blood pressure disturbances and endothelial dysfunction markers in children and adolescents with type 1 diabetes

OBJECTIVE Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. METHODS The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. RESULTS Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). CONCLUSIONS Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.

Hybrid approach to the generation of medical guidelines for insulin therapy for children

To support doctors in planning insulin therapy for juvenile diabetic patients, we propose in this paper a new approach to the generation of formal medical guidelines. In the first stage of our approach, we cluster static patients data to obtain patient cohorts with similar medical characteristics. In the second stage, for every patient of the cohort, we model the course of the disease. Using discretization and a symbolic time scale, we convert numerical data to the sequence of events. Then, we define the notion of a compound event reflecting the basic unit of the pre-meal insulin therapy. The course of the disease is modeled as a sequence of compound events. To discover the patterns of such events, we propose a new algorithm based on the concept of frequent episodes. The patterns that were obtained are presented to physicians in form of a graph that illustrates the possible pathway of the therapy. Using the proposed approach, it is possible to model both mutual similarity and repetitiveness of the prescribed treatments. The proposed method was evaluated using the actual medical data of juvenile diabetic patients. We obtained encouraging results that have been evaluated positively by doctors.

Updated 24-year trend of Type 1 diabetes incidence in children in Poland reveals a sinusoidal pattern and sustained increase

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.

Quantitative Ultrasound Bone Measurements in Pre-Pubertal Children with Type 1 Diabetes

This case-control study aimed to assess bone status in children with type 1 diabetes mellitus (T1DM). Fifty-seven pre-pubertal patients (37 boys, aged 7.9 ± 2.5 years, T1DM duration 3.1 ± 1.6 years) and 171 age-matched healthy controls (111 boys) were studied. Quantitative ultrasound (QUS) was used to measure amplitude dependent speed of sound (Ad-SoS) at hand phalanges (expressed as standard deviation score [SDS]). Anthropometric and disease-related data (including mean HbA(1c) from whole T1DM duration [T], last year [Y], examination day [D]) were collected. Mean Ad-SoS SDS in patients -0.13 ± 1.32 (95% confidence interval [CI] -0.48, 0.22) was similar to that of controls. Subgroups discriminated according to HbA(1c) D, Y and T (cut-off 7.0%) did not differ regarding analyzed parameters. In patients, Ad-SoS SDS was comparable for both genders. Multivariable stepwise regression analysis showed significant negative influence of diabetes duration on Ad-SoS SDS. QUS findings in pre-pubertal children with T1DM do not differ from those in healthy children. Disease duration seems to affect negatively Ad-SoS SDS. However, independent prospective studies are needed to elucidate the true associations.