{"entity": "journal", "iuid": "67ec3f0d9dec4ee3830a6003ebcc1784", "timestamp": "2026-07-20T22:12:10.338Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Cardiovasc%20Diabetol.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Cardiovasc%20Diabetol"}}, "title": "Cardiovasc Diabetol", "issn": "1475-2840", "issn-l": "1475-2840", "publications_count": 4, "publications": [{"entity": "publication", "iuid": "7669fdac843848fc8e7cccacb8c7519c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7669fdac843848fc8e7cccacb8c7519c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7669fdac843848fc8e7cccacb8c7519c"}}, "title": "Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays.", "authors": [{"family": "Gonz\u00e1lez-Dom\u00ednguez", "given": "\u00c1lvaro", "initials": "\u00c1"}, {"family": "Savolainen", "given": "Otto", "initials": "O"}, {"family": "Dom\u00ednguez-Riscart", "given": "Jes\u00fas", "initials": "J"}, {"family": "Landberg", "given": "Rikard", "initials": "R"}, {"family": "Lechuga-Sancho", "given": "Alfonso", "initials": "A"}, {"family": "Gonz\u00e1lez-Dom\u00ednguez", "given": "Ra\u00fal", "initials": "R"}], "type": "observational study", "published": "2024-09-11", "journal": {"title": "Cardiovasc Diabetol", "issn": "1475-2840", "volume": "23", "issue": "1", "pages": "336", "issn-l": "1475-2840"}, "abstract": "Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified.\n\nTo get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis.\n\nChildren with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals' metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels.\n\nThus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.", "doi": "10.1186/s12933-024-02395-9", "pmid": "39261864", "labels": {"Chalmers Mass Spectrometry Infrastructure": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11391635"}, {"db": "pii", "key": "10.1186/s12933-024-02395-9"}], "notes": [], "created": "2024-11-27T15:29:18.083Z", "modified": "2024-11-27T15:29:18.090Z"}, {"entity": "publication", "iuid": "85e8690a3ba2478b8c1b5e861146ca7a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/85e8690a3ba2478b8c1b5e861146ca7a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/85e8690a3ba2478b8c1b5e861146ca7a"}}, "title": "Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.", "authors": [{"family": "Gonz\u00e1lez-Dom\u00ednguez", "given": "\u00c1lvaro", "initials": "\u00c1"}, {"family": "Dom\u00ednguez-Riscart", "given": "Jes\u00fas", "initials": "J"}, {"family": "Savolainen", "given": "Otto", "initials": "O"}, {"family": "Lechuga-Sancho", "given": "Alfonso", "initials": "A"}, {"family": "Landberg", "given": "Rikard", "initials": "R"}, {"family": "Gonz\u00e1lez-Dom\u00ednguez", "given": "Ra\u00fal", "initials": "R"}], "type": "journal article", "published": "2024-08-27", "journal": {"title": "Cardiovasc Diabetol", "issn": "1475-2840", "volume": "23", "issue": "1", "pages": "315", "issn-l": "1475-2840"}, "abstract": "Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity.\n\nThe study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis.\n\nChildren with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload.\n\nAltogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.", "doi": "10.1186/s12933-024-02412-x", "pmid": "39192263", "labels": {"Chalmers Mass Spectrometry Infrastructure": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11348533"}, {"db": "pii", "key": "10.1186/s12933-024-02412-x"}], "notes": [], "created": "2024-11-27T15:29:21.274Z", "modified": "2024-11-27T15:29:21.280Z"}, {"entity": "publication", "iuid": "f7eb6438c1284992a8e9d5f25eec78ba", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f7eb6438c1284992a8e9d5f25eec78ba.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f7eb6438c1284992a8e9d5f25eec78ba"}}, "title": "Galectin-4 levels in hospitalized versus non-hospitalized subjects with obesity: the Malm\u00f6 Preventive Project.", "authors": [{"family": "Korduner", "given": "Johan", "initials": "J"}, {"family": "Holm", "given": "Hannes", "initials": "H"}, {"family": "Jujic", "given": "Amra", "initials": "A"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Pareek", "given": "Manan", "initials": "M"}, {"family": "Molvin", "given": "John", "initials": "J"}, {"family": "R\u00e5stam", "given": "Lennart", "initials": "L"}, {"family": "Lindblad", "given": "Ulf", "initials": "U"}, {"family": "Daka", "given": "Bledar", "initials": "B"}, {"family": "Leosdottir", "given": "Margret", "initials": "M"}, {"family": "Nilsson", "given": "Peter M", "initials": "PM"}, {"family": "Bachus", "given": "Erasmus", "initials": "E"}, {"family": "Olsen", "given": "Michael H", "initials": "MH"}, {"family": "Magnusson", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2022-07-02", "journal": {"title": "Cardiovasc Diabetol", "issn": "1475-2840", "volume": "21", "issue": "1", "pages": "125", "issn-l": "1475-2840"}, "abstract": "Obesity is strongly associated with the development of cardiovascular disease (CVD). However, the heterogenous nature of obesity in CVD-risk is still poorly understood. We aimed to explore novel CVD biomarkers and their possible association with presumed unhealthy obesity, defined as hospitalized subjects with obesity (HO).\n\nNinety-two proteins associated with CVD were analyzed in 517 (mean age 67 \u00b1 6 years; 33.7% women) individuals with obesity (BMI \u226530 kg/m2) from the Malm\u00f6 Preventive Project cohort, using a proximity extension array technique from the Olink CVD III panel. Individuals with at least one recorded hospitalization for somatic disease prior to study baseline were defined as HO phenotypes. Associations between proteins and HO (n = 407) versus non-hospitalized subjects with obesity (NHO, n = 110), were analyzed using multivariable binary logistic regression, adjusted for traditional risk factors.\n\nOf 92 analyzed unadjusted associations between biomarkers and HO, increased levels of two proteins were significant at a false discovery rate < 0.05: Galectin-4 (Gal-4) and insulin-like growth factor-binding protein 1 (IGFBP-1). When these two proteins were included in logistic regression analyses adjusted for age and sex, Gal-4 remained significant. Gal-4 was independently associated with the HO phenotype in multivariable logistic regression analysis (OR 1.72; CI95% 1.16-2.54). Post-hoc analysis revealed that this association was only present in the subpopulation with diabetes (OR 2.26; CI95% 1.25-4.07). However, an interaction analysis was performed, showing no significant interaction between Gal-4 and prevalent diabetes (p = 0.16).\n\nIn middle-aged and older individuals with obesity, increased Gal-4 levels were associated with a higher probability of HO. This association was only significant in subjects with diabetes only, further implying a role for Gal-4 in diabetes and its complications.", "doi": "10.1186/s12933-022-01559-9", "pmid": "35780152", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9250274"}, {"db": "pii", "key": "10.1186/s12933-022-01559-9"}], "notes": [], "created": "2022-12-02T08:47:46.066Z", "modified": "2022-12-02T08:47:46.070Z"}, {"entity": "publication", "iuid": "ae2efbc1cee84591ade32a9867a4125e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ae2efbc1cee84591ade32a9867a4125e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ae2efbc1cee84591ade32a9867a4125e"}}, "title": "Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation.", "authors": [{"family": "Kozakova", "given": "Michaela", "initials": "M"}, {"family": "Morizzo", "given": "Carmela", "initials": "C"}, {"family": "Goncalves", "given": "Isabel", "initials": "I"}, {"family": "Natali", "given": "Andrea", "initials": "A"}, {"family": "Nilsson", "given": "Jan", "initials": "J"}, {"family": "Palombo", "given": "Carlo", "initials": "C", "orcid": "0000-0002-0628-2729", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e4b4efdc7e48e086382aa6da8115c4.json"}}], "type": "journal article", "published": "2019-05-10", "journal": {"title": "Cardiovasc Diabetol", "issn": "1475-2840", "issn-l": "1475-2840", "volume": "18", "issue": "1", "pages": "61"}, "abstract": "The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM).\n\nIn T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s') and early diastolic (e') longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12.\n\nT2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e' velocity (P < 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01-0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects.\n\nThis cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.", "doi": "10.1186/s12933-019-0865-6", "pmid": "31077210", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12933-019-0865-6"}, {"db": "pmc", "key": "PMC6511166"}], "notes": [], "created": "2020-01-23T16:04:52.856Z", "modified": "2023-04-14T13:55:58.110Z"}], "created": "2020-01-23T16:04:52.870Z", "modified": "2020-11-27T13:14:03.904Z"}