1. Attachment in close relationships and glycemic outcomes in children with type 1 diabetesSimona Klemenčič, Jasna Klara Lipovšek, Anja Turin, Klemen Dovč, Nataša Bratina, Yael Shmueli-Goetz, Katarina Trebušak Podkrajšek, Barbka Repič-Lampret, Barbara Jenko Bizjan, Sašo Karakatič, Tadej Battelino, Maja Drobnič Radobuljac, 2023, izvirni znanstveni članek Povzetek: Background: Our aim was to determine whether child attachment to parents, parent attachment style, and morning cortisol levels were related to diabetes outcomes measured by average glycated hemoglobin (HbA1c), HbA1c variability over 4 years and time in range (TIR) in children with type 1 diabetes (T1D). Research design and methods: 101 children with T1D and one of their parents were assessed at baseline for child attachment (Child Attachment Interview; CAI) and parent attachment (Relationship Structures Questionnaire; ECR-RS). Serum samples were collected for cortisol measurements before the interviews. HbA1c levels were measured during a 4-year follow-up period at regular 3-monthly visits, and data for TIR were exported from blood glucose measuring devices. Multivariate linear regression models were constructed to identify independent predictors of glycemic outcomes. Results: More girls than boys exhibited secure attachment to their mothers. The results of the regression models showed that securely attached girls (CAI) had higher average HbA1c than did insecurely attached girls (B = -0.64, p = 0.03). In boys, the more insecure the parent's attachment style, the worse the child's glycemic outcome: the higher the average Hb1Ac (B = 0.51, p = 0.005), the higher the HbA1c variability (B = 0.017, p = 0.011), and the lower the TIR (B = -8.543, p = 0.002). Conclusions: Attachment in close relationships is associated with glycemic outcomes in children with T1D, and we observed significant differences between sexes. A sex- and attachment-specific approach is recommended when treating children with less favorable glycemic outcomes. Special attention and tailored support should be offered to securely attached girls in transferring responsibility for diabetes care and at least to male children of insecurely attached parents to prevent suboptimal glycemic control. Further studies in larger samples and more daily cortisol measurements may help us better understand the links between stress response, attachment and T1D. Ključne besede: attachment, childhood and adolescence, cortisol, diabetes control, time in range Objavljeno v DiRROS: 06.08.2026; Ogledov: 23; Prenosov: 16
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2. Genome-wide DNA methylation signatures in blood associated with pediatric obesityBarbara Slapnik, Robert Šket, Blaž Vrhovšek, Primož Kotnik, Tadej Battelino, Jernej Kovač, 2026, izvirni znanstveni članek Povzetek: Background: Pediatric obesity is the most prevalent nutritional disorder in children and adolescents and is associated with multiple comorbidities. Understanding epigenetic mechanisms, particularly DNA methylation, offers potential for early risk prediction, prevention, and personalized interventions. In this study, genome-wide DNA methylation profiles in blood from children with obesity and matched controls were compared using Oxford Nanopore Technologies. Two independent analytical tools were applied to identify differentially methylated regions. Clinical data included family history, weight, BMI, and age at first examination. Participants with monogenic obesity, identified via short-read whole-exome sequencing, were excluded. Results: The cohort included five girls and five boys with obesity (median age 14.33, IQR 1.65; median BMI SDS 3.42, IQR 0.55) and matched controls (median age 13.94, IQR 0.52; median BMI SDS 0.26, IQR 1.71). Seven consensus differentially methylated regions were consistently identified, overlapping genes involved in metabolism and obesity-related comorbidities. Hypermethylation was observed in PM20D1, PM20D1-AS1, AC119673.2 (26.05% ± 0.78%), and GM2A (33.60% ± 1.10%) in children with obesity, primarily affecting metabolic and adipogenic pathways. Hypomethylation was detected in genes linked to obesity and its comorbidities, including S100A14, S100A16 (- 25.4% ± 0.48%), SNTG2 (- 25.55% ± 0.18%), ADARB2, LINC00200 (- 21.35% ± 0.98%), LRRC32, AP001189.1 (- 27.25%), CBLN3 and KHNYN (- 23.20% ± 0.80%). Conclusions: Long-read genome-wide methylation profiling can detect obesity-associated epigenetic loci in children. Blood-based markers in genes regulating metabolism and obesity comorbidities could support early risk prediction, patient stratification, and targeted prevention. Extending this work to larger and more diverse cohorts will be necessary to evaluate the robustness of these results and their potential translational relevance. Ključne besede: DNA methylation, epigenetics, nanopore sequencing, pediatric obesity Objavljeno v DiRROS: 06.08.2026; Ogledov: 22; Prenosov: 15
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3. Role of HNFA1 gene variants in pancreatic beta cells function and glycaemic control in young Individuals with type 1 diabetesAntonietta Robino, Gianluca Tornese, Davide Tinti, Klemen Dovč, Valeria Castorani, Andrea Conti, Roberto Franceschini, Ivana Rabbone, Riccardo Bonfanti, Tadej Battelino, 2023, izvirni znanstveni članek Ključne besede: HNFA1 gene, beta cell function, glycaemic control Objavljeno v DiRROS: 04.08.2026; Ogledov: 77; Prenosov: 40
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4. Proposal of a familial hypercholesterolemia pediatric diagnostic score (FH-PeDS)Jan Kafol, Beatriz Miranda, Rok Šikonja, Jaka Šikonja, Albert Wiegman, Matej Mlinarič, Tadej Battelino, Urh Grošelj, 2026, izvirni znanstveni članek Ključne besede: familial hypercholesterolemia, diagnostic criteria, detection, machine learning model, cardiovascular disease, children Objavljeno v DiRROS: 27.07.2026; Ogledov: 150; Prenosov: 103
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5. Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia : a worldwide cross-sectional studyAmany Elshorbagy, Alexander R.M. Lyons, Antonio J. Vallejo-Vaz, Christophe A. T. Stevens, Kanika I. Dharmayat, Julia M. Brandts, Alberico L. Catapano, Tomas Freiberger, G. Kees Hovingh, Pedro Mata, Urh Grošelj, 2024, izvirni znanstveni članek Povzetek: Background Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30∙0 kg/m²) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74∙42 [95% CI 47∙04–117∙73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24∙42 [15∙57–38∙31]). The corresponding results in the genetically diagnosed cohort were OR 65∙04 (40∙67–104∙02) for those with obesity in the highest risk category and OR 20∙07 (12∙73–31∙65) for those without obesity. Interpretation Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population Ključne besede: Diabetes Mellitus, type 2, aged, risk factors, cross-sectional studies, sladkorna bolezen, tip 2, starostniki, dejavniki tveganja, presečne študije Objavljeno v DiRROS: 12.06.2026; Ogledov: 291; Prenosov: 223
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6. Exploring early DNA methylation alterations in type 1 diabetes : implications of glycemic controlBarbara Čugalj Kern, Jernej Kovač, Robert Šket, Tine Tesovnik, Barbara Jenko Bizjan, Julia Galhardo, Tadej Battelino, Nataša Bratina, Klemen Dovč, 2024, izvirni znanstveni članek Povzetek: Background: Prolonged hyperglycemia causes diabetes-related micro- and macrovascular complications, which combined represent a significant burden for individuals living with diabetes. The growing scope of evidence indicates that hyperglycemia affects the development of vascular complications through DNA methylation. Methods: A genome-wide differential DNA methylation analysis was performed on pooled peripheral blood DNA samples from individuals with type 1 diabetes (T1D) with direct DNA sequencing. Strict selection criteria were used to ensure two age- and sex-matched groups with no clinical signs of chronic complications according to persistent mean glycated hemoglobin (HbA1c) values over 5 years: HbA1c<7% (N=10) and HbA1c>8% (N=10). Results: Between the two groups, 8385 differentially methylated CpG sites, annotated to 1802 genes, were identified. Genes annotated to hypomethylated CpG sites were enriched in 48 signaling pathways. Further analysis of key CpG sites revealed four specific regions, two of which were hypermethylated and two hypomethylated, associated with long non-coding RNA and processed pseudogenes. Conclusions: Prolonged hyperglycemia in individuals with T1D, who have no clinical manifestation of diabetes-related complications, is associated with multiple differentially methylated CpG sites in crucial genes and pathways known to be linked to chronic complications in T1D Ključne besede: type 1 diabetes, glycemic control, DNA methylation, diabetes-related complications, long-read sequencing Objavljeno v DiRROS: 08.06.2026; Ogledov: 248; Prenosov: 183
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7. Clinical perspective on innovative insulin delivery technologies in diabetes managementGüvenç Koçkaya, Tadej Battelino, Goran Petrovski, Johan Jendle, Beatrix Sármán, Nancy Elbarbary, Damla Goksen, Mohammed Alharbi, Bird Tibet, Amir Mustapha Sharaf, 2024, izvirni znanstveni članek Povzetek: Introduction: The primary objective of this study is to report the results of an online questionnaire and the in-person discussion sessions of physicians specializing in diabetes care in which their opinions about current diabetes management was obtained. Methods: The Diabetes Innovation Summit 2023 drew attendance from a diverse group of specialized physicians from multiple countries. A comprehensive literature review was conducted to examine the technologies and medical needs associated with diabetes management. Using the results of the review, a questionnaire was developed by three experts from the steering committee to solicit feedback from specialized physicians. The online survey was made accessible between 10th December 2022 and 10th January 2023. Following the online survey, six structured in-person discussion sessions were conducted with specialized physicians from the Middle East, Central-Eastern Europe, and North Africa regions. Results: The study revealed that about 59% of survey requests were answered, with many participants being pediatric endocrinologists from North Africa. Around 60% of diabetes patients followed Multiple Daily Injections (MDI) according to specialized physicians. Among MDI users, 62% employed Blood Glucose Monitors (BGM), 31% used intermittent-scanning Continuous Glucose Monitors (isCGM), and 23% used CGM. In North Africa, nearly 90% of patients used MDI due to financial constraints. While physicians focused on both Time in Range (TIR) and HbA1c for MDI-treated patients, satisfaction with TIR achieved was expressed by 31%, while 74·1% believed Real-Time CGM (rtCGM) was effective. Concerns arose about potentially misleading HbA1c results and the relatively low patient achievement of target TIR despite CGM usage. The Smart MDI System was seen favorably compared to other applications. The system’s affordability was a significant barrier, particularly in the Middle East and Africa. Conclusion: The present study highlights that physicians are generally supportive of utilizing new technology. The questionnaires and the open discussion revealed the expectation that the Smart MDI technology provides better control, primarily by identifying missed boluses, while expressing concerns on the use of the technology by teenagers and children, who might forget the device and be reluctant to use in public, and by the older population, who might be challenged by the technology Ključne besede: diabetes treatment, glycemic control Objavljeno v DiRROS: 08.06.2026; Ogledov: 178; Prenosov: 147
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8. Genetic and clinical characteristics of patients with lipoprotein lipase deficiency from Slovenia and Pakistan : case series and systematic literature reviewQuratul Ain, Matija Cevc, Tatiana Marusic, Jaka Šikonja, Fouzia Sadiq, Urša Šuštar, Matej Mlinarič, Jernej Kovač, Hijab Batool, Iqbal Mohammad Khan, Katarina Trebušak Podkrajšek, Barbara Jenko Bizjan, Tadej Battelino, Zlatko Fras, Urh Grošelj, 2024, izvirni znanstveni članek Povzetek: Introduction: Hypertriglyceridemia (HTG) is a complex disorder caused by genetic and environmental factors that frequently results from loss-of-function variants in the gene encoding lipoprotein lipase (LPL). Heterozygous patients have a range of symptoms, while homozygous LPL deficiency presents with severe symptoms including acute pancreatitis, xanthomas, and lipemia retinalis. Methods: We described the clinical characteristics of three Slovenian patients (an 8-year-old female, an 18-year-old man, and a 57-year-old female) and one Pakistani patient (a 59-year-old male) with LPL deficiency. We performed next-generation sequencing (NGS) targeting all coding exons and intron-exon boundaries of the LPL gene, and Sanger sequencing for variant confirmation. In addition, we performed a systematic literature review of all cases with three identified variants and described their clinical characteristics. Results: Two Slovenian patients with a heterozygous pathogenic variant NM_000237.3:c.984G>T (p.Met328Ile) were diagnosed within the first three years of life and had triglyceride (TG) values of 16 and 20 mmol/L. An asymptomatic Pakistani patient with TG values of 36.8 mmol/L until the age of 44 years, was identified as heterozygous for a pathogenic variant NM_000237.3:c.724G>A (p.Asp242Asn). His TG levels dropped to 12.7 mmol/L on dietary modifications and by using fibrates. A Slovenian patient who first suffered from pancreatitis at the age of 18 years with a TG value of 34 mmol/L was found to be homozygous for NM_000237.3:c.337T>C (p.Trp113Arg). Conclusions: Patients with LPL deficiency had high TG levels at diagnosis. Homozygous patients had worse outcomes. Good diet and medication compliance can reduce severity. Ključne besede: LPL, case series, hypertriglyceridemia, lipoprotein lipase, lipoprotein lipase deficiency, pancreatitis Objavljeno v DiRROS: 08.06.2026; Ogledov: 233; Prenosov: 163
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9. Effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers in healthy 5-6-year-old children : a randomized controlled trialMaja Berlic, Mojca Korošec, Žiga Iztok Remec, Vanja Čuk, Tadej Battelino, Barbka Repič-Lampret, 2024, izvirni znanstveni članek Povzetek: As children spend up to 9 h a day in kindergarten, the main purpose of our study was to evaluate the effect of antioxidant-rich kindergarten meals on oxidative stress biomarkers (OSBs) in healthy children. In the randomized control trial with a follow-up, healthy 5–6-year-old children from six kindergartens were randomly divided into a prototype group (PG, n=40) and a control group (CG, n=17). PG followed a 2-week antioxidant-rich kindergarten meal plan (breakfast, lunch, and two snacks), and CG followed their standard kindergarten meal plans. Outside the kindergartens, participants ate as usual. We used a consecutive 7-day dietary record inside and outside the kindergarten and the national dietary assessment tool OPEN to assess the total dietary antioxidant capacity (dTAC) of the consumed foods. Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and four F2-isoprostane were measured in fasting urine on days 1 and 15. We also measured total antioxidant power (PAT) and hydroperoxides (d-ROMs) in fasting serum on day 15 and obtained the value of the oxidative stress index (OSI). We used a Welch two-sample t-test and multiple regression analysis to compare the prototype and control groups and a nonparametric Wilcoxon signed rank exact test to compare pre- and post-intervention results in urine. Antioxidant-rich kindergarten meals contributed to a significantly (p<0.05) higher intake of dTAC in PG participants compared to standard meals in CG participants (8.6 vs. 2.8 mmol/day). We detected a negative correlation between dTAC intake and d-ROMs and between dTAC intake and OSI (r= −0.29, p=0.043 and r= −0.31, p=0.032, respectively). A significant decrease in urinary 8-iso-15-prostaglandin-F-2 alpha was detected in PG participants between days 1 and 15; however, no other intra-individual significant differences in urinary OSBs were found. Ključne besede: antioxidant-rich diet, oxidative stress biomarkers, dietary antioxidant capacity, reactive oxygen metabolites, F2-isoprostanes, kindergarten diet Objavljeno v DiRROS: 08.06.2026; Ogledov: 201; Prenosov: 158
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10. The INNODIA type 1 diabetes natural history study : a European cohort of newly diagnosed children, adolescents and adultsM. Loredana Marcovecchio, A. Emile J. Hendriks, Carl Delfin, Tadej Battelino, Thomas Danne, Mark L. Evans, Jesper Johannesen, Simranjeet Kaur, Mikael Knip, Lut Overbergh, 2024, izvirni znanstveni članek Ključne besede: age, beta cell function, C-peptide, prevention, subgroups, treatment, type 1 diabetes Objavljeno v DiRROS: 05.06.2026; Ogledov: 280; Prenosov: 173
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