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Background Genotype-phenotype studies in type 1 diabetes (T1DM) patients are needed for further development of therapy strategies. Objective Our aims were to investigate the distribution of selected PTPN22 and FCRL3 gene polymorphisms and their associations with clinical course of disease in children with newly diagnosed T1DM from the Pomeranian region of Poland. Subjects/methods The prospective, longitudinal study of 147 children with newly diagnosed T1DM—autoimmune subtype was conducted. The PTPN22 c.1858T>C (rs2476601) and FCRL3 -169C>T (rs7528684) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and DNA sequencing. The frequencies of genotypes were compared between the study and population-matched control group (327 random anonymous samples from the Pomeranian region). Selected patients underwent a 24-monthly follow up [periodic re-evaluation of fasting C-peptide concentration (FCP) and hemoglobin A1c (HbA1c ) level]. Results A significantly lower coincidence of the PTPN22 c.1858CC and FCRL3 -169CC genotypes was found in the study group compared with controls (P = 0.04). The PTPN22 c.1858CC and FCRL3 -169CC genotype combination, restricted to female patients only, was associated with well-preserved residual β-cell function throughout the entire follow up (prolonged FCP level increase up to the sixth month of disease, with further very stable dynamics—FCP median level ≥0.67 ng/mL without significant decrease up to the 24th month). HbA1c levels in this subgroup also remained the lowest during the observation period. Conclusions/interpretation Ascertained phenomenon could be explained by an interacting mechanism of the two polymorphisms through estrogen-regulated nuclear factor kappa B signaling in regulatory T (Treg ) lymphocytes. This hypothesis, if confirmed, may lead to further development of Treg administration-based therapies.

Streszczenie Cel Celem pracy byla ocena zalezności pomiedzy podwyzszoną aktywnością aminotransferazy alaninowej (AIAT) a wystepowaniem zaburzen metabolicznych u otylych dzieci pochodzących z terenow wojewodztwa pomorskiego. Materialy i metody Badaniem objeto 103 otylych dzieci w wieku 2–18 lat, po raz pierwszy hospitalizowanych z powodu otylości, stale zamieszkujących na terenie wojewodztwa pomorskiego. Wyodrebniono dwie podgrupy chorych: z aktywnością AIAT ≤30 IU/l i >30 IU/l. Powyzsze dane przeanalizowano w powiązaniu z plcią, wiekiem pacjenta, wiekiem wystąpienia otylości, dlugością jej trwania, pomiarami ciśnienia tetniczego, BMI z-score, wynikami profilu lipidowego, hemoglobiny glikowanej (HbA 1c ) oraz doustnego testu tolerancji glukozy (OGTT). Wspolczynniki HOMAIR oraz HOMA-β uzyto celem oceny insulinooporności i funkcji komorek β trzustki. Wyniki Podwyzszone stezenia AIAT stwierdzono u 23 pacjentow (24,21%). Nie wykazano istotnych roznic pomiedzy czestością wystepowania zwiekszonej aktywności AIAT a plcią (p = 0,13) i wiekiem chorego (p = 0,05). W podgrupie pacjentow z aktywnością AIAT >30 IU/l stwierdzono znamiennie wyzsze wartości ciśnienia skurczowego (p = 0,03) i wyzsze poziomy insulinemii w 120 minucie OGTT (p = 0,025). Potwierdzono silną znamienną korelacje podwyzszonych stezen AIAT z czasem utrzymywania sie otylości (r = 0,42, p = 0,04). Dalsza analiza w podgrupach z uwzglednieniem plci wykazala istotną zaleznośc pomiedzy zwiekszoną aktywnością AIAT a insulinemią na czczo (p = 0,023) i HOMA-IR (p = 0,013) jedynie u chlopcow, przy jednocześnie znamiennie wyzszym u nich BMI z-score (p = 0,023). Wnioski Podwyzszona aktywnośc AIAT w związku z jej istotną korelacją z czasem utrzymywania sie otylości stanowi wazny marker zaburzen metabolicznych u otylych dzieci (zaburzen metabolizmu glukozy oraz wyzszego ryzyka nadciśnienia tetniczego). U chlopcow podwyzszone stezenia AIAT wspolistniejące z insulinoopornością mogą stanowic wazny predyktor szybszego rozwoju zaburzen metabolizmu glukozy.

Background: Diabetic ketoacidosis (DKA) development in children with new-onset type 1 diabetes (T1DM) is often the main consequence of delayed diagnosis. The aim of the study was to estimate the frequency of difficulties in T1DM diagnosis and to investigate if and how the demographic factors (gender, patient's age at presentation, family history of T1DM, level of maternal education, place of residence, and health service unit the patient called at) have any influence on diagnostic delays. Subjects and methods: Retrospective analysis of 474 children (243 boys—51.27% and 231 girls −48.73%) with new-onset T1DM aged below 17 yr and living in the Pomeranian region of Poland was carried out. The delay in diagnosis was recognized if the patient was not diagnosed on the first visit because of omission, wrong interpretation of main diabetic symptoms, exclusive treatment of additional signs, or concomitant diseases. Results: Difficulties in diagnosing T1DM were found in 67 cases (14.13%) and they are the main cause of DKA development in these children (p = 0.00). Among the examined demographic factors, mainly the patient's age at presentation has a significant influence on diagnostic delays (p = 0.01), especially in children below 2 yr (p = 0.00). Most frequently family doctors were responsible for wrong preliminary diagnosis. Conclusions: Difficulties in diagnosing T1DM are a significant cause of DKA development in children with new-onset disease. Patient's age at presentation is the main risk factor of delayed diagnosis, especially in children below 2 yr. The increase in awareness among pediatricians concerning the possibility of T1DM development in children is needed.