Stankutė, Ingrida

Type 1 diabetes (T1D) incidence is rising globally, with significant regional variation. Data from highly homogeneous populations, such as Lithuanian, may contribute to a better understanding of contributing T1D factors. This study examines 24-year trends in childhood T1D incidence and seasonal patterns in Lithuania.

Nutukimas - viena aktualiausių dabartinės visuomenės problemų, neigiamai veikianti daugelį organizmo sistemų ir trikdanti sergančiojo šia liga gyvenimo kokybę, darbingumą bei trumpinanti gyvenimą. Tai - metaboliškai aktyvi ir recidyvuojanti liga, kurios metu kūno masė didėja riebalinio audinio sąskaita. Nutukimą kaip ligą Amerikos medicinos asociacija oficialiai pripažino 2013 metais. Nutukimas pastaruoju metu yra labiausiai aptarinėjama tema tiek medicinos, tiek plačiojoje visuomenėje. Kalbant apie nutukimą, dažnai ši būklė siejama su asmeniniu kaltės priskyrimu: „reikia tik noro“, „reikia suimti save į rankas“ ir t. t. Įvairiais istoriniais laikotarpiais požiūris į žmogaus kūno formas keitėsi nuo Rubenso tipo moterų iki anoreksinių mados manekenių formų. Menamų kūno formų standartų neatitinkantis žmogus gali būti pavadintas putliu, stambiu, apkūniu, didelio dydžio ar net storuliu ar apsileidusiu. Medicinos bendruomenėje vyrauja terminai: antsvoris, hipotalaminis, pilvinis, centrinio tipo, kušingoidinis, morbidinis nutukimas ir kt. Nutukimas turi kompleksines pasekmes - skatina lėtines ligas, galinčias sutrumpinti žmogaus amžių 10-15 metų. Per pastaruosius 5 dešimtmečius nutukimo paplitimas pasaulyje padidėjo daugiau nei 3 kartus, ir dabar tai įvardijama kaip nutukimo pandemija. Klinikinėje praktikoje nustatomos įvairiausios nutukimo priežastys - nuo genetinių (Prader-Willi sindromas, Aistrom sindromas, LEPR (leptino receptoriaus) ar LEP (leptino) geno mutacijos ir kt.), endokrininių (hipotirozė, hiperkorticizmas, hipogonadizmas ir kt.) iki valgymo priklausomybių. Skirtingos yra ir nutukusių kūno formos bei kūno kompozicija. Todėl kūno masės indeksas (KMI) klinikiniu požiūriu jau nebetenka prasmės. KMI tikslinga naudoti populiaciniams, palyginamiesiems tyrimams. Statistiniais duomenimis (HIS Lietuva, Eurostat, 2019-2022 m.), pagal KMI nutukusių suaugusių Lietuvoje buvo 21-23 proc. Skaičiuojama, kad apie 60 proc. suaugusiųjų Lietuvoje turi antsvorio ar yra nutukę. Tai - tik statistika, neatspindinti konkrečios individo būklės. 2025 m. pasaulio 58 ekspertų grupė, atstovaujanti įvairioms medicinos specialybėms ir šalims, išanalizavo turimus įrodymus ir, pritarus 75 medikų ir pacientų organizacijoms, rekomendavo klasifikaciją, kurioje išskiriamas ikiklinikinis ir klinikinis nutukimas. Pagal epidemiologinius ir klinikinius duomenis, nutukimas susijęs su daugiau nei 200 skirtingų ligų ir sveikatos sutrikimų. [...]

Monogenic diabetes (MD) is a rare form of diabetes resulting from single-gene defects. While diagnostic guidelines are well established for young patients, individuals >25 years are frequently overlooked, despite the clinical value of molecular diagnosis for personalized therapy.

Pirmojo tipo cukrinis diabetas (1 tipo CD) - dažniausia lėtinė neinfekcinė vaikų liga. Nors ir didėjant sergamumui šia liga, vis dar trūksta pakankamo medikų ir visuomenės dėmesio ligos manifestacijai, kadangi, įvairių autorių duomenimis, 20,7-55% atvejų 1 tipo CD diagnozuojamas pasireiškus gyvybei grėsmingai būklei - diabetinei ketoacidozei (DKA). Šio tyrimo tikslas: išanalizuoti sergamumo bei DKA pasireiškimo dažnį Lietuvoje 2018 - 2024 m. Metodika: tai retrospektyvinis tyrimas, į kurį įtraukti duomenys apie vaikų 1 tipo CD manifestacijų. Tyrimui gautas etikos komiteto leidimas (Nr. BE-10-6). Rezultatai: 1 tipo CD sergamumo vidurkis 2018-2024 m. buvo 28,0 atvejo 100 000 vaikų (0-14 m. amžiaus), pikas 2021 m. (36,4 atv./100 000). Didžiausias sergamumas buvo 10-14 m. grupėje (p<0,01). Išanalizuoti 355 pacientų duomenys ligos pradžioje. DKA dažnio vidurkis per analizuotų laikotarpį 37,1%. Pagal DKA laipsnius: lengva DKA nustatyta - 9,9% atvejų, vidutinė - 29,3%, sunki - 21,1%. 18 pacientų diagnozės nustatymo metu pH buvo <7,0. DKA dažnis visose amžiaus grupėse buvo panašus, statistiškai nesiskyrė. Bent vienas teigiamas antikūnas nustatytas 89,9% pacientų. Teigiami GAD65 ir antikūnai prieš insuliną - po 83,4%, IA-2 - 86,2%). Visi trys teigiami žymenys nustatyti 67,3% atvejų. Išvados: 2018-2024 m. vaikų 1 tipo CD sergamumas reikšmingai padidėjo COVID-19 pandemijos metu, tačiau pastaraisiais metais stebima stabilizacija. Liga dažniausiai diagnozuojama paauglystėje, o daugiau nei trečdalis pacientų į gydymo įstaigas patenka jau su DKA, dažnai - vidutinio ar sunkaus laipsnio. Dėl to būtina didinti ligos atpažinimą ir svarstyti patikros programų diegimą, ypač turint omenyje naujus autoimuninių ligų gydymo būdus, kurie galėtų sumažinti sergamumą ir sveikatos sistemos kaštus.

Introduction Type 1 diabetes (T1D) incidence is rising globally, with significant regional variation, ranging from low rates in Asia (2. 4-3. 2 per 100, 000 person-years) to the highest in Scandinavia and Sicilia (up to 65 per 100, 000 person-years). Despite extensive research, the contributing factors — climate, genetic, environmental, or lifestylerelated, remain unclear. Therefore, data from highly homogeneous populations, such as Lithuanian, may contribute to a better understanding of these factors. This study examines 21-year trends in childhood T1D incidence andseasonal patters in Lithuania. Methods The current study relied on the incidence data sourced from the T1D Database of Lithuanian children, while population data were procured from the Lithuanian Department of Statistics. The annual incidence rates for more than two decades were computed utilizing established methodologies (per 100, 000 person-years in children aged 0-14 years (from this point onward per 100, 000 person-years). The study included 2, 472 (1221 boys) patients with T1D diagnosis before the age of 15, permanent residents of Lithuania. Results During 2001-2022, the mean standardized incidence rate (IR) was 24. 09 per 100, 000 person-years (95% CI 20. 89, 27. 28). The IR scaled from 11. 4 to 40. 8 per 100, 000 person-years, with the lowest in 2001-2002, reaching its peaks in 2017 (36. 3 per 100, 00 person-years), 2021 (40, 8 per 100, 000 person-years) and 2022 (34 per 100, 000 person-years). Analysis of the trends in age subgroups, showed the most rapid increase in young teenagers (10-14 years), with more steadily increasing incidence in younger groups (0-4 years and 5-9 years). No significant disparity in incidence trends was noticed between male and female cohorts. The boys-to-girls ratio varied from 0. 7 to 1. 53 during the study period, however, the overall ratio was 1. 00. The majority of new T1D cases (54, 5%) were diagnosed from October to March, and the lowest incidence rate was during late spring and summer months (May-July). Conclusion This study demonstrates arapidly increasing incidence of T1D in Lithuanian children over a 21-year period, with the incidence peaking at 40. 8 cases per 100, 000 personyears in 2021, rating Lithuania among the top three European countries. The seasonal distribution of new cases, with the majority occurring during the darker months of the year, suggests a potential role of reduced sunlight exposure and lower vitamin D levels, as well as increased school related stress and viral infections during autumn and wintermonths. However, additional contributing factors are likely involved, underscoring the need for further research to elucidate the underlying mechanisms driving this trend.

Introduction Monogenic diabetes (MD) is a rare form of diabetes caused by single-gene defects. Maturity-onset diabetes of the young (MODY) has well-established diagnostic guidelines in children and adolescents, but individuals over 25 are often overlooked despite the importance of molecular diagnosis for personalized treatment and family risk assessment. The “Genetic Diabetes in Lithuania” project identified GCK, HNF1A, and HNF4A as the most common MODY subtypes in Lithuanian patients up to age 25, leading to the integration of targeted genetic sequencing into clinical practice since 2017. This study aimed to analyze genetic sequencing results from a targeted MD gene panel in patients with nonautoimmune diabetes at our diabetes center from 2017 to 2022. Methods We analyzed data of 51 patient (females n Z 31 (60, 8%)) who had confirmed MODY diagnosis after targeted sequencing. The total number of patients suspected of MODY was 301, either because of negative autoimmune markers, diabetes in family history, or slight hyperglycemia, with no need for insulin treatment. Patient’s age was not considered a selection criterion for genetic counseling. Targeted gene (GCK, HNF1A, HNF4A) panel was used during 2017- 2022. The values presented as median (min;max), unless stated otherwise. Results The median age of patients was 23. 5 (7;74) years; the median duration of diabetes was 6. 0 (2;55) years at the analysis. The median age at diabetes diagnosis was 18. 3 (4;68) years. Twenty-nine (56, 9%) patients had confirmed MODY diagnosis up to the age of 25 years. Twenty-five (86, 2%) of them were diagnosed with GCK, 3 (10, 3%) – HNF1A, 1 (3, 4%) – HNF4A mutations. 65, 5% (n Z 19) had positive family history for diabetes, either MD or type 1, or type 2 diabetes. Twenty-two (43, 1%) of patients were diagnosed with MODY after the age of 25, with GCK most frequently - 17 patients (77, 3%), followed by HNF1A – 4 (18, 2%), and HNF4A – 1 (4, 5%). Eighteen (81, 8%) patients had positive family history for diabetes. Conclusions This study demonstrated a high diagnostic yield (17. 9%) for MODY among patients referred for genetic testing, with GCK mutations identified as the most prevalent etiology. Furthermore, the findings underscore the necessity of critically evaluating selection criteria for MD genetic testing, as over 40% of diagnosed cases were older than 25 years, including individuals in their late 40s and 50s. These results suggest that expanding genetic screening criteria may facilitate the identification of previously undiagnosed cases of MD, contributing to improved clinical management and risk stratification.

Introduction Monogenic diabetes (MD) makes up up to 5% of diabetes cases, with over 40 genes confirmed to cause it, though many remain unidentified. A LithuanianSwiss study identified a novel variant in the RFX2 gene, suggesting its potential role in diabetes. The study aimed to explore how RFX2 gene knockdown impacts insulin production and its clinical implications in a patient with this variant. Methods A novel c. 1894GOA (p. Ala632Thr) variant in the RFX2 gene was confirmed by PCR and Sanger sequencing. Functional analysis was performed by knocking down the gene in INS-1 832/13 cells, and insulin production was assessed using ELISA after glucose stimulation at 0 mM, 2. 5 mM, and 15 mM concentrations. Statistical analysis was conducted using IBM SPSS software 23. 0, and data are presented as median (min. -max. values). Results A 9-year-old boy diagnosed with diabetes and treated for type 1 diabetes was later found to have a novel c. 1894GOA (p. Ala632Thr) variant in the RFX2 gene at age 16. Autoantibodies for glutamic acid decarboxylase and tyrosine phosphatase-like protein were negative, though insulin autoantibodies were at the cut-off range for positivity, considering the ongoing insulin treatment, patient was suspected to have genetic diabetes. Co-segregation analysis showed no family members with diabetes signs or the same variant, prompting functional analysis of RFX2 in cell culture. Insulin production of siRFX2 cells vs. wild-type cells after stimulation with glucose (2. 5 mM) was lower, 1. 5 ! 10-5 (1. 4 ! 10-5 – 1. 7 ! 10-5) vs. 1. 6 ! 10-5 (1. 3 ! 10-5 – 1. 8 ! 10-5), respectively, P Z 0. 049. Stimulation with 15 mM glucose concentration triggered the same insulin production from both, wild-type and knocked-down cells. Insulin secretion in siRFX2 cell after using different glucose solutions, showed higher response with higher glucose concentration, 0 nM glucose - 0. 5 ! 10-5 (0. 4 ! 10-5 – 0. 8 ! 10-5); 2. 5 mM glucose –1. 5 ! 10-5 (1. 4 ! 10-5 – 1. 7 ! 10-5), 15 mM glucose - 6. 6 ! 10-5 (6. 1 ! 10-5 – 7. 6 ! 10-5), respectively, P ! 0. 001. Conclusion This experiment investigated the effect of RFX2 gene knockdown on insulin production In vitro. While the findings did not confirm RFX2 as a causative gene for monogenic diabetes, they suggested an altered glucose threshold in mutant cells, with impaired insulin production at low glucose and normal secretion at high glucose concentrations. This highlights the complexity of diabetes classification and underscores the need for further research into its etiology and pathogenesis.

Fizinis aktyvumas neabejotinai veikia neuroendokrininę sistemą ir hormonų produkciją. Individualus endokrininės sistemos atsakas priklauso nuo daugybės kintamųjų, tai ir asmens genetiniai veiksniai, amžius, lytis, biologiniai ritmai, mityba, vaistų ir papildų vartojimas, treniruotumo lygis, taip pat įtakos turi fizinio aktyvumo tipas, intensyvumas, trukmė, įvairios aplinkos sąlygos, kuriomis atliekama fizinė veikla. Šios apžvalgos tikslas yra trumpai pateikti moksliniais įrodymais pagrįstus faktus apie fizinių pratimų poveikį žmogaus organizmui, ypač neuroendokrininei sistemai, aptariant atskirų endokrininių ašių funkciją.

Introduction Diabetic ketoacidosis (DKA) is a critical and potentially life-threatening condition with a mortality rate of 9 % [1] that often occurs at the initial diagnosis of type I diabetes (T1D) in children. The presentation of DKA can vary widely among children and adolescents, often manifesting through a combination of classical symptoms such as polyuria, polydipsia, weight loss, and vomiting. These clinical signs, if correlated with specific blood gas findings like pH, bicarbonate (HCO3) levels, and base excess (BE), are essential for early diagnosis and effective management as well as prediction of the duration of hospitalization for pediatric patients with DKA [2]. Aim The aim of this study was to assess the relationships of the laboratory, clinical signs of DKA and duration of the treatment at pediatric intensive care unit (PICU) in children with T1D manifestation. Methods This is a retrospective study that was approved by Bioethics center of Lithuanian University of Health Sciences (LUHS) (2024-BEC2-1387). We analyzed data of 45 patients, treated at the Hospital of LUHS Kauno Klinikos, from July 25, 2023, to December 4, 2024. The study included all children and adolescents (0-18 years) who presented with DKA at the manifestation of T1D and came to Emergency Department at Kauno Klinikos. Clinical data as DKA symptoms, values of blood gasses, duration (in hours) of treatment at PICU were analyzed. Descriptive statistical analysis, Mann-Whitney U test, Spearman’s correlation were used for data analysis. Data is presented as median (min; max values), unless stated otherwise. P value <0.05 was considered as statistically significant, all tests were two-tailed. Statistical analysis was performed using IBM SPSS Statistics 30.0. Results This study included 45 participants, 18 (40.0 %) were female and 27 (60.0 %) male. The median age of the patients was 11 (1; 17) years. Polyuria presented in 37 (82.2 %) patients, polydipsia in 41 (91.1 %), weight loss in 30 (66.7 %), and vomiting in 12 (26.7 %). Blood gas analysis was performed for all 45 patients. The median pH value was statistically lower in patient who presented with vomiting vs. no vomiting, 7.17 (6.84; 7.41) vs 7.24 (6.89; 7.43), respectively (z=-3.126, p=0,001). No significant difference was observed when comparing pH levels in other symptom groups: polyuria vs no polyuria; polydipsia vs no polydipsia; and weight loss vs no weight loss. A negative correlation was found between the duration of treatment at PICU and initial arterial blood pH value (r=-0.470, p=0.001). Also, negative correlation was found between levels of HCO3 and duration of treatment at PICU (r=- 0.368, p=0.042). Conclusions Our study indicates that, while classical symptoms of DKA were common in children and adolescents with T1D manifestation, vomiting was significantly associated with laboratory findings, such as pH level. Lower bicarbonate levels and lower pH levels correlate with longer hospitalization at PICU.