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1.
Comparison of tandem Mass spectrometry and the fluorometric method : parallel phenylalanine measurement on a large fresh sample series and implications for newborn screening for phenylketonuria
Daša Perko, Urh Grošelj, Vanja Čuk, Žiga Iztok Remec, Mojca Žerjav-Tanšek, Ana Drole Torkar, Blaž Krhin, Ajda Biček, Adrijana Oblak, Tadej Battelino, Barbka Repič-Lampret, 2023, izvirni znanstveni članek

Povzetek: Phenylketonuria (PKU) was the first disease to be identified by the newborn screening (NBS) program. Currently, there are various methods for determining phenylalanine (Phe) values, with tandem mass spectrometry (MS/MS) being the most widely used method worldwide. We aimed to compare the MS/MS method with the fluorometric method (FM) for measuring Phe in the dried blood spot (DBS) and the efficacy of both methods in the NBS program. The FM was performed using a neonatal phenylalanine kit and a VICTOR2TMD fluorometer. The MS/MS method was performed using a NeoBaseTM 2 kit and a Waters Xevo TQD mass spectrometer. The Phe values measured with the MS/MS method were compared to those determined by the FM. The cut-off value for the NBS program was set at 120 µmol/L for FM and 85 µmol/L for MS/MS. We analyzed 54,934 DBS. The measured Phe values varied from 12 to 664 µmol/L, with a median of 46 µmol/L for the MS/MS method and from 10 to 710 µmol/L, with a median of 70 µmol/L for the FM. The Bland–Altman analysis indicated a bias of −38.9% (−23.61 µmol/L) with an SD of 21.3% (13.89 µmol/L) when comparing the MS/MS method to the FM. The Phe value exceeded the cut-off in 187 samples measured with FM and 112 samples measured with MS/MS. The FM had 181 false positives, while the MS/MS method had 106 false positives. Our study showed that the MS/MS method gives lower results compared to the FM. Despite that, none of the true positives would be missed, and the number of false-positive results would be significantly lower compared to the FM.
Ključne besede: tandem mass spectrometry, MS/MS, fluorometric method, FM, comparison, phenylalanine, Phe, phenylketonuria, PKU, newborn screening, NBS, false positive, recall rate
Objavljeno v DiRROS: 10.09.2026; Ogledov: 10; Prenosov: 10
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Exosomal MicroRNAs as theranostic tools in type 2 diabetes and its complications : mechanistic insights and clinical implications
Iva Vukelić, Art Sefedini, Dijana Detel, Sunčica Buljević, Branislav Šuša, Tine Tesovnik, Francesco Giorgino, Tadej Battelino, Dario Rahelić, Sanja Klobučar, 2026, pregledni znanstveni članek

Povzetek: Type 2 diabetes is a chronic and progressive metabolic disease, with a steadily increasing global incidence and prevalence, representing a major public health concern due to its substantial impact on morbidity and mortality. Type 2 diabetes is characterized by defective insulin secretion and peripheral insulin resistance, resulting in dysregulated glucose homeostasis. Optimal disease management is critical due to its association with multiple systemic complications, including diabetic retinopathy, nephropathy, neuropathy, foot ulcers, cardiomyopathy, and diabetes-related cognitive impairment. The involvement of exosomes in the initiation and progression of type 2 diabetes has recently gained considerable attention. These nanosized vesicles, secreted by virtually all cell types, play a pivotal role in mediating intercellular communication. This review highlights the potential of exosomes and their molecular cargo, particularly microRNAs, as endogenous biomarkers for the detection and monitoring of type 2 diabetes and its associated complications, while also exploring their emerging therapeutic applications.
Ključne besede: type 2 diabetes, diabetic complications, obesity, insulin resistance, extracellular vesicles, exosomes, MiRNAs, biomarkers, therapy
Objavljeno v DiRROS: 08.09.2026; Ogledov: 65; Prenosov: 38
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Cardiovascular and autonomic nervous system response to graded exercise in adolescents with type 1 diabetes
Tadej Rondaij, Jakob Jesih, Klemen Dovč, Tadej Battelino, Nejka Potočnik, 2026, izvirni znanstveni članek

Povzetek: Introduction: Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular and autonomic complications. Although cardiopulmonary exercise testing (CPET) is a valuable tool for assessing cardiorespiratory function, data on physiological response to maximal exertion in adolescents with T1D remain limited and inconsistent. This study aimed to compare cardiovascular, respiratory, metabolic, and microvascular responses to CPET in adolescents with T1D and healthy peers.Methods: Sixteen participants aged 11–16 years (eight with T1D and eight healthy controls), matched for anthropometric characteristics, underwent CPET on a cycle ergometer. Respiratory gas exchange, heart rate, heart rate variability, blood pressure, blood glucose, lactate concentration, skin blood flow, skin temperature, and cutaneous vascular conductance were measured at predefined time points during rest, exercise, and recovery. Blood glucose, lactate concentration, and skin microvascular variables were assessed at rest and during recovery.Results: Adolescents with T1D demonstrated a significantly lower V̇O2/power output slope and a higher ventilatory equivalent for oxygen at maximal effort, suggesting altered oxygen uptake efficiency. Maximal power output and maximal oxygen consumption did not differ between groups. Heart rate responses and heart rate variability were similar throughout testing. However, finger skin blood flow and cutaneous vascular conductance were significantly lower in the T1D group at rest and during recovery.Conclusion: Adolescents with T1D showed preserved cardiovascular function and comparable overall exercise capacity to healthy peers, despite subtle impairments in oxygen utilization and reduced skin microvascular function. These findings indicate that even at a young age, T1D is associated with altered metabolic, respiratory, and microvascular responses to maximal exercise. The results suggest that peripheral, rather than central mechanisms may underlie these differences, potentially involving glucose levels or synthetic insulin effects on vascular endothelium.
Ključne besede: autonomic nervous system, cardiovascular system, exercise testing, microcirculation, oxygen uptake, type 1 diabetes
Objavljeno v DiRROS: 07.09.2026; Ogledov: 61; Prenosov: 43
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LDL hypercholesterolemia in children : genetic influence and response to lifestyle advice - follow-up of the Fr1dolin-trial
Stefan Arens, Urša Šuštar, Karin Lange, Thomas Danne, Tadej Battelino, Urh Grošelj, Olga Kordonouri, 2026, izvirni znanstveni članek

Povzetek: Background and aims: Although familial hypercholesterolemia (FH) is common and associated with significant cardiovascular morbidity, screening programs are scarce. Furthermore, the effectiveness of nutritional advice for parents on children’s LDL cholesterol (LDL-C) levels is unclear, especially in FH versus non-FH hypercholesterolemia. Methods: In the Fr1dolin study, 367 of 14,513 children in Lower Saxony and Hamburg were positively screened for LDL hypercholesterolemia with an LDL-C>135 mg/dl (>3.5 mmol/l). The screening was considered positive if the first finding of hypercholesterolemia was confirmed in a second sample. These 367 children were invited to a follow-up examination including an extended lipid status, nutritional counseling and genetic analysis. Results: 289 out of 367 screen-positive children (57.4% girls) were followed up for 12 months; 191 (66.1%) underwent genetic testing. Children with a FH-causing pathogenic or likely pathogenic variant (n=40, 20.9%) had significantly higher LDL-C levels than children without a variant or with a variant of uncertain significance (p<0.001). After the nutritional counselling and after 6 and 12 months of follow-up, LDL-C levels did not improve significantly (median LDL-C at baseline 142 mg/dl, and 140 mg/dl at 6 and 12 months follow-up, respectively). Conclusions: A population-based screening program detects LDL-hypercholesterolemia in up to 2.5% of children, with a significant proportion of them having FH genetic variants, supporting early detection. One-time nutritional advice had little effect on LDL-C in general, but particularly in FH, highlighting on the one hand need for structured lifestyle programs and on the other hand early genetic testing in population based FH screening.
Ključne besede: familial hypercholesterolemia, FH, screening, children, LDL-C, nutritional advice, lifestyle intervention, follow-up study
Objavljeno v DiRROS: 04.09.2026; Ogledov: 96; Prenosov: 50
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7.
Association between electronic cigarette use and prediabetes, diabetes, and insulin resistance : a systematic review and meta-analysis
Yusuff Adebayo Adebisi, Davide Campagna, Antonio Ceriello, Anas Ali Alhur, Najim Z. Alshahrani, Anoop Misra, Abdul Basit, Cristina Russo, Tadej Battelino, Noel Somasundaram, 2026, izvirni znanstveni članek

Povzetek: Electronic cigarette (e-cigarette) use has grown rapidly worldwide, yet metabolic health consequences, particularly glycaemic outcomes, remain poorly understood. This systematic review and meta-analysis synthesises the available epidemiological evidence on the association between e-cigarette use and diabetes mellitus, prediabetes, and insulin resistance. We conducted a systematic search of PubMed, Scopus and Embase from inception through December 2025, following PRISMA 2020 guidelines. Studies reporting effect estimates for the association between e-cigarette use and diabetes, prediabetes, or insulin resistance in adult populations were eligible. Random-effects meta-analyses were performed, stratified by outcome and exposure category (current exclusive e-cigarette users, dual users, and former e-cigarette users versus never users). Heterogeneity was assessed using I2 statistics and Cochran’s Q test. Ten studies (9 cross-sectional, 1 prospective cohort; combined participants exceeding 2.8 million) met inclusion criteria; 8 cross-sectional studies contributed to quantitative pooling, while one cross-sectional study and the prospective cohort were narratively synthesised. For prediabetes, pooled ORs versus never users were 1.34 (95% CI 1.01–1.77; I2 = 74.2%) for current exclusive users, 1.26 (1.06–1.49; I2 = 75.4%) for dual users, and 1.13 (1.06–1.20; I2 = 0%) for former users. For diabetes, only dual users showed a significant elevation (OR 1.23; 1.01–1.49; I2 = 77.4%); current exclusive (OR 1.04; 0.93–1.16; I2 = 45.1%) and former users (OR 1.11; 0.80–1.54; I2 = 31.6%) did not differ from never users. For insulin resistance, current exclusive e-cigarette users versus never users had an OR of 1.37 (95% CI 1.06–1.77; I2 = 0%). The sole prospective cohort study found no significant association between exclusive e-cigarette use and incident type 2 diabetes (HR 0.88; 95% CI 0.66–1.16). Neither cross-sectional nor prospective evidence linked exclusive e-cigarette use to diabetes; significant associations were confined to dual users. Elevated odds of prediabetes and insulin resistance among exclusive users were observed cross-sectionally but cannot support causal claims. Large prospective studies with longer follow-up, objective verification of product exposure status (for example, biomarkers distinguishing exclusive vaping from combustible tobacco use), and standardised laboratory-based glycaemic endpoints are needed.
Ključne besede: electronic cigarettes, e-cigarettes, vaping, diabetes mellitus, prediabetes, insulin resistance
Objavljeno v DiRROS: 04.09.2026; Ogledov: 79; Prenosov: 50
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From global guidelines for cardio-kidney-metabolic diseases management to national implementation : perspectives from the guideline workshop taskforce
Christoph Wanner, Francesco Cosentino, Katharine Barnard-Kelly, Tadej Battelino, Matthias Blüher, Helena N. Boll, Frank Brosius, Luca Busetto, Antonio Ceriello, James R. Gavin, 2026, drugi znanstveni članki

Povzetek: International guidelines define standards of care for type 2 diabetes (T2D), obesity, cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD). Yet implementation at the national level remains inconsistent, leading to persistent gaps between evidence-based recommendations and real-world practice. Key barriers include linguistic and cultural adaptation, limited communication to clinicians, and siloed regulatory and reimbursement processes. Addressing these challenges requires coordinated strategies, such as concise translations, digital platforms and decision-support tools, integration into medical education, and structured monitoring and evaluation frameworks with feedback and incentives. Equitable and sustainable access further depends on coordination between medical societies, governmental authorities, payers, and patient representatives. Evidence from existing initiatives shows that systematic, context-sensitive approaches can measurably improve care. Building on these lessons, this Commentary recommends priorities for national implementation to ensure that guidelines move more effectively from publication to practice and realise their full potential to improve patient outcomes.
Ključne besede: clinical practice guideline implementation, diabetes, obesity, cardiovascular disease, chronic kidney disease
Objavljeno v DiRROS: 04.09.2026; Ogledov: 103; Prenosov: 51
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9.
Somapacitan in children with idiopathic short stature : a randomized controlled phase 3 study
M. Jennifer Abuzzahab, Andrew Dauber, Michael Højby Rasmussen, Kamil Soltysik, Masanobu Kawai, Philip G. Murray, Moshe Phillip, Tadej Battelino, 2026, izvirni znanstveni članek

Povzetek: Objective: Daily growth hormone (GH) injections restore normal growth and improve psychological outcomes in children with idiopathic short stature (ISS) but treatment burden is significant. The objective of this study is to demonstrate efficacy and safety of once-weekly somapacitan, a long-acting GH, in children with ISS. Design: REAL8 (ClinicalTrials.gov: NCT05330325) is a global, randomized, open-labelled, active-comparator, phase 3 basket study including 4 non-GH deficiency indications comprising a 52-week main phase and 104-week extension. Here, we present 52-week results from the REAL8 ISS study. Methods: Eighty-eight pre-pubertal, treatment-naive children with ISS at clinics in 20 countries were randomized 2:1 to somapacitan .24 mg/kg/week or daily GH 0.050 mg/kg/day, both administered subcutaneously. Eighty-five children completed the main 52-week treatment period. Results: Observed mean height velocity, HV, (SD) at week 52 was 10.2 (1.7) and 10.6 (1.6) cm/year for somapacitan and daily GH groups, respectively (estimated treatment difference [ETD]: −0.3 cm/year [-1.00;0.42]95%CI, non-inferiority confirmed). Safety profiles were similar (somapacitan: 191 events in 47 (79.7%) participants, daily GH: 87 events in 22 (78.6%) participants) with most adverse events (AEs) mild and unlikely related to study product. Disease and treatment burden questionnaires presented favourable results. Conclusions: Similar efficacy and safety were confirmed for once-weekly somapacitan versus daily GH in treatment-naïve children with ISS, with favourable patient-reported outcome measures, setting the ground for future treatment for ISS with a once-weekly option.
Ključne besede: idiopathic short stature, growth hormone therapy, long-acting growth hormone, somapacitan
Objavljeno v DiRROS: 04.09.2026; Ogledov: 94; Prenosov: 46
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10.
Transcriptomics of type 1 diabetes progression : a validation study in newly diagnosed patients
Tomi Suomi, Inna Starskaia, Omid Rasool, Ubaid Ullah Kalim, Sylvaine F. A. Bruggraber, M. Loredana Marcovecchio, Emile Hendricks, Lut Overbergh, Mark Peakman, Timothy Tree, 2026, izvirni znanstveni članek

Povzetek: Background: Type 1 diabetes is an autoimmune disease with significant long-term complications. Variability in the decline of insulin secretion after diagnosis complicates both the development of treatments and disease management. We previously reported that gene expression changes within the first year post-diagnosis were associated with C-peptide decline at two years in the first INNODIA cohort of patients with newly diagnosed type 1 diabetes. Here, we aimed to validate these findings in an independent follow-up cohort and to increase statistical power by combining the data from both cohorts. Methods: We analysed transcriptomic data from a follow-up INNODIA cohort of 168 individuals with newly diagnosed type 1 diabetes to assess whether previously identified associations with disease progression could be replicated. We then combined data from the original and follow-up cohorts for integrated analysis. Longitudinal gene expression changes during the first year after diagnosis were examined in relation to disease progression, alongside age and estimated immune cell abundances. Findings: Analysis of the follow-up cohort validated the previously observed longitudinal changes in gene expression during the first year after diagnosis. In the combined dataset, transcriptomic analysis identified a large number of genes that were differentially expressed during the first year after disease onset. More rapid disease progression was associated with younger age and a relative decrease in neutrophil abundance. In addition, changes in the expression of several genes were associated with the rate of disease progression. Interpretation: These findings support the existence of biological heterogeneity in disease progression after diagnosis of type 1 diabetes and contribute to an improved understanding of the molecular dynamics associated with disease progression. These findings may help future studies aiming to enable patient stratification and design of more targeted and personalised therapeutic approaches in type 1 diabetes.
Ključne besede: type 1 diabetes, transcriptomics, beta cell decline, C-peptide, disease progression
Objavljeno v DiRROS: 04.09.2026; Ogledov: 100; Prenosov: 61
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