1. The role of vascular lesions in diabetes across a spectrum of clinical kidney diseaseRosa Rodriguez-Rodriguez, Radovan Hojs, Francesco Trevisani, Enrique Morales, Gema Fernández, Sebastjan Bevc, Clara Maria Cases Corona, Josep Maria Cruzado, María Quaro, Maruja Navarro Díaz, Mads Hornum, Beatriz Fernandez-Fernandez, Arianna Bettiga, Federico Di Marco, Marina López Martínez, Francisco J. Moreso, Clara García Garro, Khaled Khazim, Fedaa Ghanem, Manuel Praga, Meritxell Ibernón, Ivo Laranjinha, Luís Mendonça, Miguel Bigotte Vieira, Bo Feldt-Rasmussen, Patricia Fox Concepción, Natalia Negrín Mena, Alberto Ortiz, Esteban L. Porrini, 2021, izvirni znanstveni članek Opis: Introduction: The clinical-histologic correlation in diabetic nephropathy is not completely known.
Methods: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR).
Results: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III.
Conclusions: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes. Ključne besede: albuminuria, chronic kidney disease, diabetes, diabetic nephropathy, histology, normoalbuminuria Objavljeno v DKUM: 06.12.2024; Ogledov: 0; Prenosov: 3 Celotno besedilo (1,56 MB) Gradivo ima več datotek! Več... |
2. Cognitive and emotional perceptions of illness in patients diagnosed with type 2 diabetes mellitusLucija Gosak, Gregor Štiglic, 2024, izvirni znanstveni članek Opis: Type 2 diabetes mellitus (T2DM) affects a patient’s physical, social, and mental well-being. Perceptions of the illness are linked to quality of life. The aim of this study was to assess illness perception in patients diagnosed with T2DM and to validate the Brief Illness Perception Questionnaire in the Slovenian language. A cross-sectional study involved 141 patients diagnosed with T2DM. We performed a content analysis of the questionnaire and estimated the S-CVI, I-CVI, kappa coefficient. We also used Cronbach’s alpha to assess the reliability. Participants did not have a very threatening perception of T2DM, but being overweight and having cardiovascular disease were significant contributors to a more threatening perception. The most frequently indicated factors influencing the onset and development of T2DM were heredity and genetics, stress and other psychological distress, and poor and inadequate nutrition. I-CVI ranged from 0.833 to 1.00, while the kappa is greater than 0.74, confirming the excellent validity of the questions. The content validity assessment of the questionnaire further confirms that the questionnaire is suitable for use with the target population in Slovenia. The questionnaire proved to be a valid and reliable tool that can be used to assess the relationship between illness perception and self-management of T2DM. Ključne besede: type 2 diabetes mellitus (T2DM), illness perception, psychometric properties Objavljeno v DKUM: 28.11.2024; Ogledov: 0; Prenosov: 0 Celotno besedilo (236,42 KB) Gradivo ima več datotek! Več... |
3. Application of transmission electron microscopy to detect changes in pancreas physiologyMaša Skelin, Jurij Dolenšek, Ismael Valladolid-Acebes, Andraž Stožer, Saška Lipovšek Delakorda, 2022, samostojni znanstveni sestavek ali poglavje v monografski publikaciji Ključne besede: pancreas physiology, exocrine cells, endocrine cells, ultrastructure, metabolic syndrome, type 2 diabetes mellitus, western diet Objavljeno v DKUM: 24.09.2024; Ogledov: 0; Prenosov: 1 Povezava na datoteko |
4. Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic ▫$\alpha$▫-cellsVladimir Grubelnik, Rene Markovič, Saška Lipovšek Delakorda, Gerd Leitinger, Marko Gosak, Jurij Dolenšek, Ismael Valladolid-Acebes, Per-Olof Berggren, Andraž Stožer, Matjaž Perc, Marko Marhl, 2020, izvirni znanstveni članek Opis: Type 2 diabetes mellitus (T2DM) has been associated with insulin resistance and the failure of β-cells to produce and secrete enough insulin as the disease progresses. However, clinical treatments based solely on insulin secretion and action have had limited success. The focus is therefore shifting towards α-cells, in particular to the dysregulated secretion of glucagon. Our qualitative electron-microscopy-based observations gave an indication that mitochondria in α-cells are altered in Western-diet-induced T2DM. In particular, α-cells extracted from mouse pancreatic tissue showed a lower density of mitochondria, a less expressed matrix and a lower number of
cristae. These deformities in mitochondrial ultrastructure imply a decreased efficiency in mitochondrial ATP production, which prompted us to theoretically explore and clarify one of the most challenging problems associated with T2DM, namely the lack of glucagon secretion in hypoglycaemia and its oversecretion at high blood glucose concentrations. To this purpose, we constructed a novel computational model that links α-cell metabolism with their electrical activity and glucagon secretion. Our results show that defective mitochondrial metabolism in α-cells can
account for dysregulated glucagon secretion in T2DM, thus improving our understanding of T2DM pathophysiology and indicating possibilities for new clinical treatments.
Ključne besede: diabetes, pancreatic alpha cells, glucagon, mitochondrial dysfunction, free fatty acid Objavljeno v DKUM: 03.09.2024; Ogledov: 49; Prenosov: 4 Celotno besedilo (1,60 MB) Gradivo ima več datotek! Več... |
5. Mitochondrial dysfunction in pancreatic alpha and beta cells associated with type 2 diabetes mellitusVladimir Grubelnik, Jan Zmazek, Rene Markovič, Marko Gosak, Marko Marhl, 2020, izvirni znanstveni članek Opis: Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30-40% reduction in alpha cells' mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases. Ključne besede: pancreatic endocrine cells, mathematical model, mitochondrial dysfunction, cellular bioenergetics, diabetes, glucagon, insulin Objavljeno v DKUM: 03.09.2024; Ogledov: 47; Prenosov: 8 Celotno besedilo (1,63 MB) Gradivo ima več datotek! Več... |
6. Mechanisms of post-pancreatitis diabetes mellitus and cystic fibrosis-related diabetes: a review of preclinical studiesEleonóra Gál, Jurij Dolenšek, Andraž Stožer, László Czakó, Attila Ébert, Viktória Venglovecz, 2021, pregledni znanstveni članek Opis: Anatomical proximity and functional correlations between the exocrine and endocrine pancreas warrant reciprocal effects between the two parts. Inflammatory diseases of the exocrine pancreas, such as acute or chronic pancreatitis, or the presence of cystic fibrosis disrupt endocrine function, resulting in diabetes of the exocrine pancreas. Although novel mechanisms are being increasingly identified, the intra- and intercellular pathways regulating exocrine-endocrine interactions are still not fully understood, making the development of new and more effective therapies difficult. Therefore, this review sought to accumulate current knowledge regarding the pathogenesis of diabetes in acute and chronic pancreatitis, as well as cystic fibrosis. Ključne besede: diabetes of the exocrine pancreas, acute pancreatitis, chronic pancreatitis, cystic fibrosis, interaction Objavljeno v DKUM: 14.08.2024; Ogledov: 65; Prenosov: 5 Celotno besedilo (955,04 KB) Gradivo ima več datotek! Več... |
7. Peer support as part of scaling-up integrated care in patients with type 2 diabetes and arterial hypertension at the primary healthcare level : a study protocolTina Virtič, Matic Mihevc, Črt Zavrnik, Majda Mori-Lukančič, Tonka Poplas-Susič, Zalika Klemenc-Ketiš, 2023, izvirni znanstveni članek Opis: Introduction: Type 2 diabetes (T2D) and arterial hypertension (AH) are among the greatest challenges facing health systems worldwide and require comprehensive patient-centred care. The key to successful management in chronic patients is self-management support, which was found to be only weakly implemented in Slovenia. The aim of the study is to develop an evidence-based model of peer support for people with T2D and AH at the primary healthcare level in Slovenia, which could represent a potential solution for upgrading integrated care for these patients.
Methods: A prospective interventional, mixed-methods pilot study will begin by recruiting approximately 40 eligible people with T2D and AH through purposive sampling. The participants will receive structured training, led by a specialist nurse, to become trained peer supporters. Each will voluntarily share their knowledge and experience at monthly group meetings with up to 10 people with T2D and AH over a three-month period in the local community. Data will be collected through interviews and focus groups and questionnaires about socio-demographic and clinical data, knowledge about T2D and AH, participants’ quality of life, level of empowerment and acceptability of the intervention.
Expected results: The study will provide an evidence-based model for integrating peer support into the local community. It is expected that the intervention will prove feasible and acceptable with educational, psychosocial and behavioural benefits.
Conclusion: Peer support through empowerment of people with T2D and AH, family members and other informal caregivers in the local community could scale-up the integrated care continuum and contribute to sustainability of the healthcare system. Ključne besede: diabetes type 2, arterial hypertension, peer support, self-management, integrated primary, healthcare Objavljeno v DKUM: 17.07.2024; Ogledov: 103; Prenosov: 4 Celotno besedilo (304,20 KB) Gradivo ima več datotek! Več... |
8. Process evaluation of the scale-up of integrated diabetes and hypertension care in Belgium, Cambodia and Slovenia (the SCUBY Project) : a study protocolMonika Martens, Edwin Wouters, Josefien Van Olmen, Zalika Klemenc-Ketiš, Srean Chhim, Savina Chham, Verle Buffel, Katrien Danhieux, Nataša Stojnić, Črt Zavrnik, Tonka Poplas-Susič, Win Van Damme, Por Ir, Roy Remmen, Grace Marie V Ku, Kerstin Klipstein-Grobusch, Daniel Boateng, 2022, izvirni znanstveni članek Opis: Introduction Integrated care interventions for type 2 diabetes (T2D) and hypertension (HT) are effective, yet challenges exist with regard to their implementation and scale-up. The ‘SCale-Up diaBetes and hYpertension care’ (SCUBY) Project aims to facilitate the scale-up of integrated care for T2D and HT through the co-creation and implementation of contextualised scale-up roadmaps in Belgium, Cambodia and Slovenia. We hereby describe the plan for the process and scale-up evaluation of the SCUBY Project. The specific goals of the process and scale-up evaluation are to (1) analyse how, and to what extent, the roadmap has been implemented, (2) assess how the differing contexts can influence the implementation process of the scale-up strategies and (3) assess the progress of the scale-up.
Methods and analysis A comprehensive framework was developed to include process and scale-up evaluation embedded in implementation science theory. Key implementation outcomes include acceptability, feasibility, relevance, adaptation, adoption and cost of roadmap activities. A diverse range of predominantly qualitative tools—including a policy dialogue reporting form, a stakeholder follow-up interview and survey, project diaries and policy mapping—were developed to assess how stakeholders perceive the scale-up implementation process and adaptations to the roadmap. The role of context is considered relevant, and barriers and facilitators to scale-up will be continuously assessed.
Ethics and dissemination Ethical approval has been obtained from the Institutional Review Board (ref. 1323/19) at the Institute of Tropical Medicine (Antwerp, Belgium). The SCUBY Project presents a comprehensive framework to guide the process and scale-up evaluation of complex interventions in different health systems. We describe how implementation outcomes, mechanisms of impact and scale-up outcomes can be a basis to monitor adaptations through a co-creation process and to guide other scale-up interventions making use of knowledge translation and co-creation activities. Ključne besede: diabetes and hypertension care, Belgium, Cambodia, Slovenia Objavljeno v DKUM: 27.06.2024; Ogledov: 139; Prenosov: 8 Celotno besedilo (1,50 MB) Gradivo ima več datotek! Več... |
9. The effects of diabetes and being overweight on patients with post-COVID-19 syndromeSimona Kirbiš, Nina Sobotkiewicz, Barbara Antolinc Schaubach, Jernej Završnik, Peter Kokol, Matej Završnik, Helena Blažun Vošner, 2023, izvirni znanstveni članek Ključne besede: post-COVID-19 syndrome, diabetes, overweight, COVID-19 pneumonia, observational study Objavljeno v DKUM: 13.06.2024; Ogledov: 124; Prenosov: 17 Celotno besedilo (580,73 KB) Gradivo ima več datotek! Več... |
10. Role of cAMP in double switch of glucagon secretionJan Zmazek, Vladimir Grubelnik, Rene Markovič, Marko Marhl, 2021, izvirni znanstveni članek Opis: Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+ -dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATPdependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution
of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of "secure double switch". The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence. Ključne besede: pancreatic alpha cell, glucagon, cAMP, mathematical model, diabetes, cellular bioenergetics Objavljeno v DKUM: 06.06.2024; Ogledov: 107; Prenosov: 11 Celotno besedilo (2,58 MB) Gradivo ima več datotek! Več... |