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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: 142; Prenosov: 75
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Povzetek: Continuous glucose monitoring (CGM) is increasingly used although not officially registered for the management of people liv-ing with liver glycogen storage diseases (GSDs). The aims of this study were twofold: (a) to investigate the current experiencesof healthcare providers (HCPs), patients, and caregivers using CGM to monitor glucose concentrations in liver GSDs, and (b)to formulate consensus statements. Two web-based questionnaires were distributed, one for HCPs and one for patients and/ortheir caregivers. The questionnaires collected data on demographics and epidemiology, current use of CGM, and opinions andstatements about CGM in GSDs. For the statements, respondents rated their agreement on a 5-point Likert scale, and the consen-sus level was set at 75%. One Hundred Fourteen HCPs (including 87 physicians and 26 dietitians) from 28 countries responded,representing care of approximately 3800 liver GSD patients. Additionally, 148 GSD patients and/or their caregivers from 21 coun-tries responded, mainly representing GSD Ia (n = 50), GSD Ib (n = 56), GSD III (n = 14), and GSD IX (n = 18). The median age toconsider starting to use CGM was 6 and 2 months for HCPs and GSD families, respectively. Out of 16 statements common to thetwo questionnaires, HCPs and patients/caregivers reached consensus on 12 statements in both groups. Use of CGM is consideredstandard of care by both HCPs and GSD families, but reimbursement of CGM devices is challenging. Compared to diabetes melli-tus, CGM should be applied differently in liver GSDs. Consensus guidelines are warranted on the use of CGM in liver GSDs, bothin routine healthcare and in clinical trials.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,provided the original work is properly cited.© 2025 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.Terry G. J. Derks and Ruben J. Overduin are shared first authors.Sarah C. Grünert and Alessandro Rossi are shared last authors.The Members of the CGM GSD Collaborators Group are given in Appendix A.Abbreviations: CGM, continuous glucose monitoring; DM, diabetes mellitus; FBS, Fanconi-Bickel syndrome; GSD, glycogen storage disease; HCP, healthcareprovider; SMBG, self-monitoring blood glucose; TAR, time above range; TBR, time below range; TIR, time in range.
Ključne besede: glycemic control, management, rare disease. survey, CGM, GSD, glycogen storage disease
Objavljeno v DiRROS: 09.03.2026; Ogledov: 320; Prenosov: 217
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Povzetek: Background and aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD. Results: Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77-48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10-2.63 and odds ratio 1.65, 95% confidence interval 1.27-2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations. Conclusions: Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.
Ključne besede: dyslipidaemia, adiposity, insulin resistance, atherosclerosis
Objavljeno v DiRROS: 27.02.2026; Ogledov: 297; Prenosov: 330
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Povzetek: Background: Branched-chain amino acid transaminase 2 (BCAT2) deficiency is an autosomal recessive disorder that impairs branched-chain amino acid (BCAA) catabolism. Its clinical and metabolic features remain poorly understood due to limited reports in the literature. Methods: We report three novel cases of BCAT2 deficiency from Slovenia: one diagnosed following symptom onset, one through cascade screening of parents, and one by newborn screening. Diagnosis was established through metabolic evaluation and confirmation of pathogenic variants in the BCAT2 gene. In addition, we performed a systematic review of all previously reported cases of BCAT2 deficiency. Results: All three patients were homozygous for the NM_001190.4:c.600C > A (p.Tyr200Ter) variant, with valine concentrations at presentation of 2093, 2589, and 794 μmol/L. Only one patient was symptomatic, presenting with headaches, developmental delay, and intellectual disability, while the remaining two were largely asymptomatic. Notably, insulin resistance was observed in one of the three patients and may be associated with elevated BCAA levels. Systematic literature review identified 8 additional cases of BCAT2 deficiency. Genetic variant c.600C > A was also found in two Pakistani individuals, while the remaining variants were each reported in only a single individual. The most common clinical characteristics were intellectual disability (55%), developmental delay and other neurological symptoms (36%). Abnormal white matter findings on MRI were observed in all patients who underwent imaging. BCAA levels decreased in all patients receiving pyridoxine supplementation; however, only 50% showed clinical improvement. Conclusion: BCAT2 deficiency displays marked interindividual heterogeneity, ranging from asymptomatic cases to severe neurological impairment, which renders its pathogenicity uncertain.
Ključne besede: BCAT2, branched-chain amino acids, antihistamine branched-chain amino acid transaminase, hypervalinemia, hyperleucine-isoleucinemia, insulin resistance, white matter abnormalities
Objavljeno v DiRROS: 19.01.2026; Ogledov: 461; Prenosov: 290
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Povzetek: Familial hypercholesterolemia (FH) is the most common metabolic disease, with prevalence estimated between 1:250 and 1:300. The affected individuals have a significantly higher risk for developing atherosclerosis and cardiovascular disease (CVD) compared to non-affected individuals. Early CVD can be prevented with early detection and treatment of FH. In Slovenia we have been conducting a national three-staged program of universal screening for FH of preschoolers. Goals: Our goal is to collect data for 5000 children, which is approximately one-quarter of one generation of preschoolers for the year 2023 (n = 5000). Methods: Our study includes both prospective and retrospective components and is a non-interventional cohort study. The prospective component began in 2023, when a questionnaire was distributed to multiple community health centers and outpatient practices in Slovenia. Pediatricians or school medicine specialists completed these questionnaires. The retrospective component involves our research team collecting the remaining necessary data from existing medical records. We are going to follow our algorithm for the implementation of the universal cholesterol screening program and seek all children that will be referred to the Pediatric Lipid Clinic at the University Children’s Hospital, University Medical Centre (UCH-UMC), Ljubljana, for further genetic testing. If a child has a positive genetic result, their parents and siblings will undergo genetic testing. Conclusions: Despite being a common genetic disorder, familial hypercholesterolemia (FH) is still largely underdiagnosed globally; fewer than 10% of affected individuals are thought to be identified. Early detection through effective screening is therefore essential to improve outcomes and prevent premature cardiovascular events.
Ključne besede: hypercholesterolemia, universal screening, preschoolers, total cholesterol, genetic testing
Objavljeno v DiRROS: 11.12.2025; Ogledov: 657; Prenosov: 321
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