المؤلفون: Kennedy, Beatrice, 1982, Varotsis, Georgios, Hammar, Ulf, Nguyen, Diem, PhD, Carrasquilla, Germán D., van Zoest, Vera, 1992, Kristiansson, Robert S., Fitipaldi, Hugo, Dekkers, Koen F., Daivadanam, Meena, Martinell, Mats, 1971, Björk, Jonas, Fall, Tove, 1979

المصدر: European Journal of Public Health. 34(1):14-21

الوصف: BackgroundDiagnostic testing is essential for disease surveillance and test–trace–isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates.MethodsWe included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8–1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood.ResultsWe observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5–69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5–14 years) ranging from 0.56 (95% CI 0.47–0.67) to 0.87 (95% CI 0.80–0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10–18% decrease in inhabitants 15–29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70–105, supporting an intervention effect.ConclusionsEnsuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-528378Test
https://doi.org/10.1093/eurpub/ckad209Test
https://uu.diva-portal.org/smash/get/diva2:1859256/FULLTEXT01.pdfTest

المؤلفون: Gustafsson, Stefan, Lampa, Erik, Jensevik Eriksson, Karin, Butterworth, Adam S., Elmståhl, Sölve, Engström, Gunnar, Hveem, Kristian, Johansson, Mattias, Langhammer, Arnulf, Lind, Lars, Läll, Kristi, Masala, Giovanna, Metspalu, Andres, Moreno-Iribas, Conchi, Nilsson, Peter M., Perola, Markus, Simell, Birgit, Sipsma, Hemmo, Åsvold, Bjørn Olav, Ingelsson, Erik, Hammar, Ulf, Ganna, Andrea, Svennblad, Bodil, Fall, Tove, Sundström, Johan

المصدر: Nature Cardiovascular Research EpiHealth: Epidemiology for Health. 3(2):130-139

مصطلحات موضوعية: Medicin och hälsovetenskap, Klinisk medicin, Kardiologi, Medical and Health Sciences, Clinical Medicine, Cardiac and Cardiovascular Systems

الوصف: Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.

الوصول الحر: https://lup.lub.lu.se/record/afdfc207-ab94-48e5-b73b-bbea13982b25Test
http://dx.doi.org/10.1038/s44161-024-00422-2Test

المؤلفون: Sayols-Baixeras, Sergi, Dekkers, Koen F, Baldanzi, Gabriel, Jönsson, Daniel, Hammar, Ulf, Lin, Yi-Ting, Ahmad, Shafqat, Nguyen, Diem, Varotsis, Georgios, Pita, Sara, Nielsen, Nynne, Eklund, Aron C, Holm, Jacob B, Nielsen, H Bjørn, Ericson, Ulrika, Brunkwall, Louise, Ottosson, Filip, Larsson, Anna, Ericson, Dan, Klinge, Björn, Nilsson, Peter M, Malinovschi, Andrei, Lind, Lars, Bergström, Göran, Sundström, Johan, Ärnlöv, Johan, Engström, Gunnar, Smith, J Gustav, Orho-Melander, Marju, Fall, Tove

المصدر: Circulation EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden. 148(6):459-472

مصطلحات موضوعية: Medicin och hälsovetenskap, Klinisk medicin, Kardiologi, Medical and Health Sciences, Clinical Medicine, Cardiac and Cardiovascular Systems

الوصف: BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.

الوصول الحر: https://lup.lub.lu.se/record/cbc855fe-a443-406e-8df4-177a569e794cTest
http://dx.doi.org/10.1161/CIRCULATIONAHA.123.063914Test

المؤلفون: Williamson, Alice, Norris, Dougall M, Yin, Xianyong, Broadaway, K Alaine, Moxley, Anne H, Vadlamudi, Swarooparani, Wilson, Emma P, Jackson, Anne U, Ahuja, Vasudha, Andersen, Mette K, Arzumanyan, Zorayr, Bonnycastle, Lori L, Bornstein, Stefan R, Bretschneider, Maxi P, Buchanan, Thomas A, Chang, Yi-Cheng, Chuang, Lee-Ming, Chung, Ren-Hua, Clausen, Tine D, Damm, Peter, Delgado, Graciela E, de Mello, Vanessa D, Dupuis, Josée, Dwivedi, Om P, Erdos, Michael R, Silva, Lilian Fernandes, Frayling, Timothy M, Gieger, Christian, Goodarzi, Mark O, Guo, Xiuqing, Gustafsson, Stefan, Hakaste, Liisa, Hammar, Ulf, Hatem, Gad, Herrmann, Sandra, Højlund, Kurt, Horn, Katrin, Hsueh, Willa A, Hung, Yi-Jen, Hwu, Chii-Min, Jonsson, Anna, Kårhus, Line L, Kleber, Marcus E, Kovacs, Peter, Lakka, Timo A, Lauzon, Marie, Lee, I-Te, Lindgren, Cecilia M, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Luan, Jian’an, Aly, Dina Mansour, Mathiesen, Elisabeth, Moissl, Angela P, Morris, Andrew P, Narisu, Narisu, Perakakis, Nikolaos, Peters, Annette, Prasad, Rashmi B, Rodionov, Roman N, Roll, Kathryn, Rundsten, Carsten F, Sarnowski, Chloé, Savonen, Kai, Scholz, Markus, Sharma, Sapna, Stinson, Sara E, Suleman, Sufyan, Tan, Jingyi, Taylor, Kent D, Uusitupa, Matti, Vistisen, Dorte, Witte, Daniel R, Walther, Romy, Wu, Peitao, Xiang, Anny H, Zethelius, Björn, Ahlqvist, Emma, Bergman, Richard N, Chen, Yii-Der Ida, Collins, Francis S, Fall, Tove, Florez, Jose C, Fritsche, Andreas, Grallert, Harald, Groop, Leif, Hansen, Torben, Koistinen, Heikki A, Komulainen, Pirjo, Laakso, Markku, Lind, Lars, Loeffler, Markus, März, Winfried, Meigs, James B, Raffel, Leslie J, Rauramaa, Rainer, Rotter, Jerome I, Schwarz, Peter EH, Stumvoll, Michael

المصدر: Nature Genetics. 55(6)

مصطلحات موضوعية: Biochemistry and Cell Biology, Genetics, Biological Sciences, Diabetes, Clinical Research, Human Genome, Prevention, Nutrition, 2.1 Biological and endogenous factors, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Metabolic and endocrine, Humans, Insulin, Genome-Wide Association Study, Insulin Resistance, Diabetes Mellitus, Type 2, Glucose, Blood Glucose, Meta-Analysis of Glucose and Insulin-related Traits Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology

الوصف: Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/23k400p7Test

المؤلفون: Baldanzi, Gabriel, Sayols-Baixeras, Sergi, Ekblom-Bak, Elin, Ekblom, Örjan, Dekkers, Koen F., Hammar, Ulf, Nguyen, Diem, Ahmad, Shafqat, Ericson, Ulrika, Arvidsson, Daniel, Börjesson, Mats, Johanson, Peter J., Smith, J. Gustav, Bergström, Göran, Lind, Lars, Engström, Gunnar, Ärnlöv, Johan, Kennedy, Beatrice, Orho-Melander, Marju, Fall, Tove

المصدر: EBioMedicine EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden. 100

مصطلحات موضوعية: Accelerometery, Epidemiology, Exercise, Gastrointestinal microbiome, Sedentary behaviour, Medicin och hälsovetenskap, Hälsovetenskap, Arbetsmedicin och miljömedicin, Medical and Health Sciences, Health Sciences, Environmental Health and Occupational Health

الوصف: Background: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study. Methods: In 8416 participants aged 50–65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing. Findings: Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity. Interpretation: Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species. Funding: European Research Council, Swedish Heart-Lung Foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation.

الوصول الحر: https://lup.lub.lu.se/record/59dd698e-633c-415e-ba2e-7ec8a9f2e15fTest
http://dx.doi.org/10.1016/j.ebiom.2024.104989Test

المؤلفون: Baldanzi, Gabriel, Sayols-Baixeras, Sergi, Theorell-Haglöw, Jenny, Dekkers, Koen F., Hammar, Ulf, Nguyen, Diem, Lin, Yi Ting, Ahmad, Shafqat, Holm, Jacob Bak, Nielsen, Henrik Bjørn, Brunkwall, Louise, Benedict, Christian, Cedernaes, Jonathan, Koskiniemi, Sanna, Phillipson, Mia, Lind, Lars, Sundström, Johan, Bergström, Göran, Engström, Gunnar, Smith, J. Gustav, Orho-Melander, Marju, Ärnlöv, Johan, Kennedy, Beatrice, Lindberg, Eva, Fall, Tove

المصدر: Chest EpiHealth: Epidemiology for Health EXODIAB: Excellence of Diabetes Research in Sweden. 164(2):503-516

مصطلحات موضوعية: epidemiology, microbiota, OSA, Medicin och hälsovetenskap, Klinisk medicin, Kardiologi, Medical and Health Sciences, Clinical Medicine, Cardiac and Cardiovascular Systems

الوصف: Background: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Research Question: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? Study Design and Methods: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. Results: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. Interpretation: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

الوصول الحر: https://lup.lub.lu.se/record/a13068b8-cb2b-4789-808b-e6d647b6ca0fTest
http://dx.doi.org/10.1016/j.chest.2023.03.010Test

المؤلفون: Broadaway, K. Alaine, Yin, Xianyong, Williamson, Alice, Parsons, Victoria A., Wilson, Emma P., Moxley, Anne H., Vadlamudi, Swarooparani, Varshney, Arushi, Jackson, Anne U., Ahuja, Vasudha, Bornstein, Stefan R., Corbin, Laura J., Delgado, Graciela E., Dwivedi, Om P., Silva, Lilian Fernandes, Frayling, Timothy M., Grallert, Harald, Gustafsson, Stefan, Hakaste, Liisa, Hammar, Ulf, Herder, Christian, Herrmann, Sandra, Højlund, Kurt, Hughes, David A., Kleber, Marcus E., Lindgren, Cecilia M., Liu, Ching Ti, Luan, Jian'an, Malmberg, Anni, Moissl, Angela P., Morris, Andrew P., Perakakis, Nikolaos, Peters, Annette, Petrie, John R., Roden, Michael, Schwarz, Peter E.H., Sharma, Sapna, Silveira, Angela, Strawbridge, Rona J., Tuomi, Tiinamaija, Wood, Andrew R., Wu, Peitao, Zethelius, Björn, Baldassarre, Damiano, Eriksson, Johan G., Fall, Tove, Florez, Jose C., Fritsche, Andreas, Gigante, Bruna, Hamsten, Anders, Kajantie, Eero, Laakso, Markku, Lahti, Jari, Lawlor, Deborah A., Lind, Lars, März, Winfried, Meigs, James B., Sundström, Johan, Timpson, Nicholas J., Wagner, Robert, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Barroso, Inês, O'Rahilly, Stephen, Grarup, Niels, Parker, Stephen CJ, Boehnke, Michael, Langenberg, Claudia, Wheeler, Eleanor, Mohlke, Karen L.

المساهمون: Institute for Molecular Medicine Finland, Faculty Common Matters (Faculty of Medicine), HUS Abdominal Center, Department of Psychology and Logopedics, Centre of Excellence in Complex Disease Genetics, Tiinamaija Tuomi Research Group, Clinicum, Endokrinologian yksikkö, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital

مصطلحات موضوعية: colocalization, conditional, enhancer, eQTL, fine-mapping, GWAS, meta-analysis, proinsulin, signal, type 2 diabetes, 515 Psychology

الوصف: Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10−8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: Broadaway , K A , Yin , X , Williamson , A , Parsons , V A , Wilson , E P , Moxley , A H , Vadlamudi , S , Varshney , A , Jackson , A U , Ahuja , V , Bornstein , S R , Corbin , L J , Delgado , G E , Dwivedi , O P , Silva , L F , Frayling , T M , Grallert , H , Gustafsson , S , Hakaste , L , Hammar , U , Herder , C , Herrmann , S , Højlund , K , Hughes , D A , Kleber , M E , Lindgren , C M , Liu , C T , Luan , J , Malmberg , A , Moissl , A P , Morris , A P , Perakakis , N , Peters , A , Petrie , J R , Roden , M , Schwarz , P E H , Sharma , S , Silveira , A , Strawbridge , R J , Tuomi , T , Wood , A R , Wu , P , Zethelius , B , Baldassarre , D , Eriksson , J G , Fall , T , Florez , J C , Fritsche , A , Gigante , B , Hamsten , A , Kajantie , E , Laakso , M , Lahti , J , Lawlor , D A , Lind , L , März , W , Meigs , J B , Sundström , J , Timpson , N J , Wagner , R , Walker , M , Wareham , N J , Watkins , H , Barroso , I , O'Rahilly , S , Grarup , N , Parker , S CJ , Boehnke , M , Langenberg , C , Wheeler , E & Mohlke , K L 2023 , ' Loci for insulin processing and secretion provide insight into type 2 diabetes risk ' , American Journal of Human Genetics , vol. 110 , no. 2 , pp. 284-299 . https://doi.org/10.1016/j.ajhg.2023.01.002Test; ORCID: /0000-0003-4347-1788/work/150687442; ORCID: /0000-0002-4310-5297/work/150699098; ORCID: /0000-0002-8306-6202/work/150744093; 85147458360; 64f667eb-102c-4118-b626-2a13e1deebb1; http://hdl.handle.net/10138/569676Test

الإتاحة: http://hdl.handle.net/10138/569676Test

المؤلفون: Lind, Lars, Salihovic, Samira, Associate Senior Lecturer, 1985, Sundström, Johan, Elmståhl, Sölve, Hammar, Ulf, Dekkers, Koen, Ärnlöv, Johan, Smith, J. Gustav, Engström, Gunnar, Fall, Tove

المصدر: Journal of Clinical Endocrinology and Metabolism. 107(5):1337-1345

مصطلحات موضوعية: Epidemiology, insulin resistance, metabolic syndrome, metabolomics, obesity

الوصف: CONTEXT: There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not.OBJECTIVE: We aimed to compare the plasma metabolome in obese subjects without the metabolic syndrome (MetS) to normal-weight subjects without MetS, as well as to obese subjects with MetS.DESIGN: Cross-sectional.SETTING: Two academic centers in Sweden.PARTICIPANTS: Three population-based samples (EpiHealth, n=2342, SCAPIS-Uppsala, n=4985 and SCAPIS-Malmö, n=3978) in which individuals were divided into groups according to their BMI and presence/absence of MetS (NCEP/consensus criteria).INTERVENTION: None.MAIN OUTCOME MEASURE: 791 annotated endogenous metabolites measured by ultra-performance liquid chromatography tandem mass spectrometry.RESULTS: We observed major differences in metabolite profiles (427 metabolites) between obese (BMI ≥ 30 kg/m 2) and normal-weight (BMI < 25 kg/m 2) subjects without MetS after adjustment for major life-style factors. Pathway enrichment analysis highlighted branch-chained and aromatic amino acid synthesis/metabolism, aminoacyl-tRNA biosynthesis and sphingolipid metabolism. The same pathways, and similar metabolites, were also highlighted when obese subjects with and without MetS were compared despite adjustment for BMI and waist circumference, or when the metabolites were related to BMI and number of MetS components in a continuous fashion. Similar metabolites and pathways were also related to insulin sensitivity (Matsuda index) in a separate study (POEM, n=501).CONCLUSION: Our data suggest a graded derangement of the circulating metabolite profile from lean to obese to the metabolic syndrome, in particular for metabolites involved in amino acid synthesis/metabolism and sphingolipid metabolism. Insulin resistance is a plausible mediator of this gradual metabolic deterioration.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-96288Test
https://doi.org/10.1210/clinem/dgab922Test

المؤلفون: Ahmad, Shafqat, Hammar, Ulf, Kennedy, Beatrice, Salihovic, Samira, Associate Senior Lecturer, 1985, Ganna, Andrea, Lind, Lars, Sundström, Johan, Ärnlöv, Johan, Berne, Christian, Risérus, Ulf, Magnusson, Patrik Ke., Larsson, Susanna C., Fall, Tove

المصدر: Diabetes. 71(2):329-339

الوصف: Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-95508Test
https://doi.org/10.2337/db20-1120Test

المؤلفون: Druvefors, Emma, Andersson, Roland E., Hammar, Ulf, Landerholm, Kalle, Myrelid, Par

المصدر: Alimentary Pharmacology and Therapeutics. 56(2):292-300

مصطلحات موضوعية: Crohn's disease, fertility, inflammatory bowel disease, men, ulcerative colitis

الوصف: Background and Aims Onset of inflammatory bowel disease (IBD) in men is most common during childbearing age, but little is known about the impact on fertility. Previous studies of fertility in men were small, which justifies this large nation-based registry study.Methods Fertility was assessed in a national cohort of men with IBD aged 15-44 years in 1964-2014, identified from the Swedish National Patient Register, and in a reference cohort matched for age and place of residence (ratio 1:5). Information about childbirths was found in the Swedish Multi-Generation Register. Patients with indeterminate colitis or inconsistent IBD coding were classified as IBD-unclassified (IBD-U).Results The cohorts included 29,104 men with IBD and 140,901 matched individuals. IBD patients had a lower fertility rate (number of births per 1000 person years) compared with the matched individuals; 1.28 (SD 1.27) versus 1.35 (SD 1.31; p < 0.001). Fertility was somewhat impaired in all IBD subtypes compared with the matched cohort; ulcerative colitis (UC) (hazard ratio [HR] 0.93, 95% CI 0.91-0.96), Crohn's disease (CD) (HR 0.95, 95% CI 0.92-0.98) and IBD-U 0.92, 95% CI 0.89-0.95. The cumulated total parity and the parity progression were also decreased for all IBD subtypes. Within the IBD cohort disease severity, intensity of medical treatment (CD) and bowel surgery (IBD-U) were further associated with impaired fertility.Conclusions This nationwide cohort study shows only slightly impaired fertility in men with IBD.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485095Test
https://doi.org/10.1111/apt.16984Test
https://uu.diva-portal.org/smash/get/diva2:1697131/FULLTEXT01.pdfTest