Stankutė, Ingrida

Introduction: WAGR syndrome is a rare contiguous gene deletion disorder characterized by the classical tetrad: Wilms tumor, aniridia, genitourinary anomalies, and a spectrum of developmental delays. It is caused by a deletion on chromosome 11p13, typically involving critical genes such as WT1 and PAX6. Objectives: To present a rare clinical case of WAGR syndrome with multisystem involvement, including endocrine and metabolic abnormalities. Methods: A 4-year-old girl was referred to a pediatric endocrinologist due to rapid weight gain and metabolic disturbances. Her anthropometric measurements were: height 100.2 cm (10th–25th percentile), weight 19 kg (75th–90th percentile), and BMI 18.92 kg/m² (approaching the 97th percentile). Laboratory evaluation revealed fasting hyperglycemia (up to 5.84 mmol/L) with insulin resistance (HOMA-IR 3.63), and central hypothyroidism (low TSH and low FT4). Previous medical history: she was the first child in the family. Aniridia was diagnosed shortly after birth. At the age of 1.5 years, she was diagnosed with nephroblastoma (Wilms tumor) of the right kidney. Given the suspicion of a rare syndromic condition, the patient was referred for genetic evaluation. Results: Genetic testing identified a pathogenic heterozygous deletion >7 Mb on chromosome 11p13, encompassing multiple genes including PAX6, WT1, BDNF, FSHB, DCDC1, ELP4, RCN1, HIPK3, and CD44. Haploinsufficiency of WT1, PAX6, and BDNF is considered central to the patient’s phenotype, contributing to tumor predisposition, ocular abnormalities, and neurodevelopmental and metabolic features. Conclusions: This case highlights the critical role of genetic testing in patients with congenital anomalies and multisystem involvement. WAGR syndrome may also present with endocrine and metabolic disturbances, including obesity, insulin resistance, and hypothyroidism. Early diagnosis and coordinated multidisciplinary management are essential to optimize clinical outcomes.

Introduction: Physiological response and the role of the incretins are well-characterized in healthy individuals. However, there is limited data regarding the incretin-insulin axis in patients with monogenic diabetes (MD). Objectives: Evaluate the timing between GLP-1 and C-peptide peaks during a mixed meal tolerance test (MMTT). By comparing GCK, HNF1A, HNF4A patients vs. healthy controls, we aim to assess β-cell responsiveness and incretin sensitivity across different MD types. Methods: 17 subjects with GCK diabetes (median age 15.3 yrs (IQR 13.6 – 17.8 yrs); 6 - HNF1A, with a median age 20.0 yrs (IQR 15.2 – 23.8 yrs); and two - HNF4A diabetes, aged 24.5 and 25.9 yrs. Control group consisted of 19 subjects (median age 23.2 yrs (IQR 22.6 – 24.6 yrs). C-peptide and GLP-1 levels were measured at 9 time points during a standard MMTT. Area under the curve (AUC) was calculated using the trapezoidal method. An incretin responsiveness index was defined as AUCC-peptide divided AUCGLP-1. GLP-1 – to – C-peptide lag analysis: lag=Tmax (C-peptide) – Tmax (GLP-1). Mann–Whitney U test was used for group comparisons. Results: The incretin responsiveness index was significantly reduced across all MD subtypes. Compared to controls 78.6 [62.4– 96.8], the index was lower in GCK 32.1 [24.7–41.3], p< 0.00001; in HNF1A 27.4 [21.9–33.8, p=0.0004; and in HNF4A 1.08 [0.89–1.27, p=0.0002. GLP-1–to–C-peptide lag differed across groups. Controls demonstrated a median lag of 0 min. (IQR 0–45), while GCK showed marked variability with a wide range including negative values (median 0, IQR −60 to 30). In contrast, HNF1A and HNF4A exhibited a more consistent positive lag (median 30 min.), indicating delayed but preserved temporal coupling. Conclusions: The incretin responsiveness index demonstrated a stepwise impairment in incretin-mediated β-cell responsiveness: Controls->GCK->HNF1A->HNF4A, suggesting the failure of β-cells to respond appropriately in time.

BACKGROUND: Klippel–Feil syndrome is a rare congenital anomaly characterised by a clinical triad consisting of a low posterior hairline, a short neck, and restricted cervical mobility [1]. Although the hallmark feature of this disorder is congenital fusion of the cervical vertebrae, it may also present with extraskeletal manifestations and additional spinal abnormalities [2]. THE CASE: A 5-year-10-month-old girl was referred to pediatric endocrinologists for evaluation of short stature and developmental delay. From the medical history, girl was born at 37 weeks of gestation (length of 42 cm and weight of 2230 g) via vaginal delivery in breech presentation. Congenital clubfoot and developmental dysplasia of the hips were diagnosed. A spinal MRI performed in the same year revealed Klippel–Feil syndrome, kyphotic deformity at the Th8–Th12 levels, vertebrae Th9 and Th10 resembling hemivertebrae, and spina bifida in the sacral region; neurosurgical intervention was performed. Genetic testing demonstrated a 46, XX karyotype without major chromosomal abnormalities. At 6 years old, during evaluation by a pediatric endocrinologist, her height was 94 cm (12 cm below the 3rd percentile), and weight was 13.7 kg. Body mass index (BMI) was 15.4 (50th percentile). The patient had a proportional body build. No abnormalities were observed in other systems. Radiography of the left hand demonstrated a bone age of 6 years 9 months (chronological age 5 years 10 months), adult height of 125 cm was predicted. A growth hormone stimulation test with glucagon showed an adequate response (peak GH 101.4 mU/L), thereby excluding GH deficiency. Further follow-up was recommended due to suspected primary IGF-1 deficiency. At age 8, repeated genetic consultation identified a duplication of uncertain clinical significance, 638 kb in size, located on the long arm of chromosome 9 arr[GRCh37]9q31.1(103338012_103976442) x3. There was insufficient evidence for a chromosomal disorder. At age 10, the patient was re-examined by a pediatric endocrinologist for the same complaints. At that time, her height was 113 cm and weight 20 kg, with a BMI of 15.66. The patient wears a brace due to scoliosis. No abnormalities were detected in other systems. Serum IGF-1 concentration was 19.9 nmol/L (reference range 24.6–67.3). Therefore, the prognosis for final height was considered poor due to underlying skeletal deformities and the primary syndrome. CONCLUSION: This case highlights a rare manifestation of Klippel-Feil syndrome in which persistent short stature developed despite normal growth hormone secretion. Genetic testing revealed a chromosomal duplication of uncertain significance, expanding the spectrum of possible genotype-phenotype correlations in this syndrome. Early detection of skeletal and spinal anomalies allowed timely structural interventions, but the long-term multisystemic impact, including orthopedic deformities, neurological sequelae, and growth concerns, required ongoing multidisciplinary management to optimize functional outcomes and quality of life. Recently observed low IGF 1 level warrant ongoing monitoring and may indicate evolving endocrine involvement. While current treatment strategies remain primarily supportive, targeted endocrine therapies such as recombinant IGF 1 replacement have shown benefit in select primary IGF 1 deficiency conditions and could represent a potential avenue for future investigation, although evidence specific to Klippel-Feil syndrome is currently lacking.

Diabetinė ketoacidozė (DKA) - ūmi ir gyvybei pavojinga būklė, kuri atsiranda dėl insulino stygiaus, kortizolio, augimo hormono, gliukagono, katecholaminų aktyvumo padidėjimo. Tyrimai rodo, kad Covid-19 pandemija 2021 metais turėjo reikšmingą įtaką ketoacidozės dažnio padidėjimui tarp vaikų iki 18 metų amžiaus. Metodika: Atliktas retrospektyvinis tyrimas, į kurį įtraukti vaikai iki 18 metų amžiaus, kurie 2018, 2021 ir/ar 2024 metais kreipėsi į LSMUL KK Vaikų Skubios pagalbos skyrių (SPS) dėl cukriniam diabetui būdingų simptomų ar jų paūmėjimo. Tyrimui gautas etikos komiteto leidimas (Nr. BE-10-6). Rezultatai: Analizuotu laikotarpiu į SPS kreipėsi 231 pacientas, tačiau į tyrimą įtraukti 93 pacientai (vidutinis tiriamųjų amžius - 10 metų; jauniausias pacientas - 1 m. amžiaus, o vyriausias - 17 m.), atitinkantys diabetinės ketoacidozės diagnostikos kriterijus, iš kurių 33 (35,5 %) pacientų kreipėsi jau turėdami 1 tipo CD diagnozę, o kiti pacientai - 60 (64,5 %) buvo nauji 1 tipo CD atvejai. 2021 metais, pandemijos piko metu, fiksuotas didžiausias diagnozuotų DKA pacientų skaičius - 39 pacientai (41,9 %) ir, palyginti su 2018 ir 2024 metais, kreipėsi daugiau sunkų DKA laipsnį turinčių naujai diagnozuotų CD pacientų. Vertinant rūšiavimo efektyvumų analizuotais laikotarpiais, pastebėta, kad iš 3 kategorijai priskirtų 62 pacientų: 19 buvo sunkios diabetinės ketoacidozės, 18 - vidutinio sunkumo ir 25 - lengvos formos DKA. Išvados: Dažniausiai į vaikų SPS kreipėsi pacientai, turintys sunkų diabetinės ketoacidozės (DKA) laipsnį. Tai pabrėžia būtinybę gerinti šios būklės klinikinį atpažinimų ir tobulinti pacientų rūšiavimo procesus skubios pagalbos skyriuose, siekiant užtikrinti savalaikę ir tinkamą pagalbą.

Aims: To test the hypothesis that continuous glucose monitoring (CGM) metrics are independently associated with cardiovascular risk factor (CVRF) exposure, particularly low‐density lipoprotein cholesterol (LDL‐C) and blood pressure (BP), in youth with type 1 diabetes (T1D) enrolled in the international SWEET registry.
Materials and Methods:
This cross‐sectional study included youth aged 6–18 years with T1D duration ≥ 1 year, not receiving antihypertensive or lipid‐lowering therapy and with available CGM profiles (≥ 14 days), lipid and BP data between January 2019 and June 2023. Associations between CGM metrics and LDL‐C or BP were analysed using multiple linear regression, adjusted for sex and pubertal status (model 1) and additionally for body mass index–SDS (model 2), diabetes duration (model 3) and HbA1c (model 4).
Results: Data from 3328 subjects (median age 14.3 years, T1D duration 5.6 years, 52.2% male) were analysed. Time in range (TIR) and time in tight range (TITR) were inversely associated with BP-SDS and LDL-C, while time above range (TAR), mean glucose, glucose variability (coefficient of variation (CV)) [%] and glycemia risk index showed positive associations (all p < 0.01). In multivariable regression models 1–3, TIR, TITR, TAR and glycemia risk index remained independently associated with LDL-C and systolic BP-SDS (p < 0.001), with CV also independently associated with systolic BP-SDS (p < 0.001). In model 4 associations with SBP-SDS were attenuated, whereas those with LDL-C remained significant, although with a reversal direction. Conclusions : Key CGM metrics, particularly TIR and TITR, are independently associated with LDL-C and BP in youth with T1D, highlighting their potential clinical relevance in the assessment of cardiovascular risk profile, alongside HbA1c.

Background Digital diabetes technologies support self-management, yet their real-world use and patient experience may differ between T1DM and T2DM. Methods A cross-sectional survey was conducted in Lithuania among adults with diabetes and parents of children with T1DM. Questionnaires assessed demographics, use of diabetes technologies, usability, professional support, and satisfaction. Data from 159 respondents (T1DM n=117, T2DM n=42) were included. Group comparisons were performed using descriptive statistics and chi-square tests. The study was a part of the project received funding from Research Council of Lithuania (LMTLT), agreement No S-THCS-25-1 under the frame of Transforming Health and Care Systems, THCS, (GA N° 101095654 of the EU Horizon Europe Research and Innovation Programme) Results Mean age was 38±12.8 years in T1DM and 62±9.9 years in T2DM. CGM use was significantly higher in T1DM than T2DM (43.6% vs 11.6%, p<0.001); insulin pumps were used only in T1DM (22.2%). Physical activity apps were more common in T1DM (17.9% vs 4.7%, p=0.037). Most T1DM participants felt comfortable using technologies (76.9% vs 20.9%, p<0.001) but more often considered discontinuation (14.5% vs 2.3%, p<0.001). Adequate professional support was reported more frequently by T2DM participants (88% vs 53%, p<0.001). The main perceived benefit was improved DM control in both groups, while the main barrier was a confusing user interface. Detail information in Table 1. Conclusions T1DM adults use advanced diabetes technologies more frequently but experience greater technology burden. T2DM adults report better professional support despite lower uptake. Improving usability and structured education may enhance sustainable technology use across diabetes types.

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.