Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-23

AUTHORS

Thomas Bryrup, Cæcilie W. Thomsen, Timo Kern, Kristine H. Allin, Ivan Brandslund, Niklas R. Jørgensen, Henrik Vestergaard, Torben Hansen, Tue H. Hansen, Oluf Pedersen, Trine Nielsen

ABSTRACT

AIMS/HYPOTHESIS: Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment. METHODS: Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6 weeks. Inclusion criteria were men of age 18-35 years, BMI between 18.5 kg/m2 and 27.5 kg/m2, HbA1c < 39 mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2 months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1 g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit. RESULTS: Data from participants who completed visit 1 (n=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of Intestinibacter spp. and Clostridium spp., as well as an increased abundance of Escherichia/Shigella spp. and Bilophila wadsworthia. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects. CONCLUSIONS/INTERPRETATION: Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies. TRIAL REGISTRATION: Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050 FUNDING: This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation. More... »

PAGES

1-12

References to SciGraph publications

  • 2013-06. Gut metagenome in European women with normal, impaired and diabetic glucose control in NATURE
  • 2016-07. DADA2: High-resolution sample inference from Illumina amplicon data in NATURE METHODS
  • 2018-11-05. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin in NATURE MEDICINE
  • 2012-09-26. A metagenome-wide association study of gut microbiota in type 2 diabetes in NATURE
  • 1985-07. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man in DIABETOLOGIA
  • 2017-12. Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas in BMC GENOMICS
  • 2015-10. Prediction and validation of enzyme and transporter off-targets for metformin in JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
  • 2015-12. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota in NATURE
  • 2015-04-06. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats in NATURE MEDICINE
  • 2017-07. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug in NATURE MEDICINE
  • 2014-06. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase in NATURE
  • 2013-01-06. Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00125-019-4848-7

    DOI

    http://dx.doi.org/10.1007/s00125-019-4848-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112964833

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30904939


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Clinical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University of Copenhagen", 
              "id": "https://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bryrup", 
            "givenName": "Thomas", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Copenhagen", 
              "id": "https://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Thomsen", 
            "givenName": "C\u00e6cilie W.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Copenhagen", 
              "id": "https://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kern", 
            "givenName": "Timo", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Bispebjerg Hospital", 
              "id": "https://www.grid.ac/institutes/grid.411702.1", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark", 
                "Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Allin", 
            "givenName": "Kristine H.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Southern Denmark", 
              "id": "https://www.grid.ac/institutes/grid.10825.3e", 
              "name": [
                "Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark", 
                "Institute of Regional Health Research, University of Southern Denmark (SDU), Odense C, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Brandslund", 
            "givenName": "Ivan", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Southern Denmark", 
              "id": "https://www.grid.ac/institutes/grid.10825.3e", 
              "name": [
                "Dept of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark", 
                "Odense Patient data Explorative Network (OPEN), Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "J\u00f8rgensen", 
            "givenName": "Niklas R.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Steno Diabetes Center", 
              "id": "https://www.grid.ac/institutes/grid.419658.7", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark", 
                "Steno Diabetes Center Copenhagen, Gentofte, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Vestergaard", 
            "givenName": "Henrik", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Southern Denmark", 
              "id": "https://www.grid.ac/institutes/grid.10825.3e", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark", 
                "Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hansen", 
            "givenName": "Torben", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Slagelse Hospital", 
              "id": "https://www.grid.ac/institutes/grid.452905.f", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark", 
                "Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hansen", 
            "givenName": "Tue H.", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Copenhagen", 
              "id": "https://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Pedersen", 
            "givenName": "Oluf", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Copenhagen", 
              "id": "https://www.grid.ac/institutes/grid.5254.6", 
              "name": [
                "Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Nielsen", 
            "givenName": "Trine", 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/nature12198", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002791386", 
              "https://doi.org/10.1038/nature12198"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11450", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004546178", 
              "https://doi.org/10.1038/nature11450"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.3787", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005202989", 
              "https://doi.org/10.1038/nm.3787"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0002-9343(97)00254-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1005252023"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1017/s0007114516004086", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008159895"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1078/07232020260517625", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1008890102"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/gutjnl-2012-303839", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009561639"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci40671", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012086379"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci40671", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012086379"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature15766", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014535385", 
              "https://doi.org/10.1038/nature15766"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature15766", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1014535385", 
              "https://doi.org/10.1038/nature15766"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/gutjnl-2014-308778", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016218646"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2337/dc15-0488", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016430875"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3389/fmicb.2016.01706", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016587504"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nmeth.3869", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016631324", 
              "https://doi.org/10.1038/nmeth.3869"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature11808", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016730403", 
              "https://doi.org/10.1038/nature11808"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/mbio.00261-11", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017408208"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0009085", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017487904"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.aad3503", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1017663631"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1136/gutjnl-2014-307873", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1019463103"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature13270", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024050118", 
              "https://doi.org/10.1038/nature13270"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00280883", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027902786", 
              "https://doi.org/10.1007/bf00280883"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00280883", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027902786", 
              "https://doi.org/10.1007/bf00280883"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00280883", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027902786", 
              "https://doi.org/10.1007/bf00280883"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0006-2952(99)00396-2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1028761556"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s10928-015-9436-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033261734", 
              "https://doi.org/10.1007/s10928-015-9436-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1185/03007998409109558", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034198355"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1111/dom.12811", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1035154399"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2147/dmso.s43731", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037910058"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci13505", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043705336"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci13505", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1043705336"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1128/aem.00062-07", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045980007"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.aad3369", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049864477"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2337/dc13-2817", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051706700"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2337/dc16-1324", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1070730310"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2337/dc16-1324", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1070730310"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.2337/diacare.15.6.755", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1070745705"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/ajcn/85.5.1185", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1077415617"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078621898", 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.4345", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085459595", 
              "https://doi.org/10.1038/nm.4345"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm.4345", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1085459595", 
              "https://doi.org/10.1038/nm.4345"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/s12864-017-4195-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1092272577", 
              "https://doi.org/10.1186/s12864-017-4195-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1084/jem.20171965", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100421130"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1084/jem.20171965", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1100421130"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0204317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107281380"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0204317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107281380"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1371/journal.pone.0204317", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107281380"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/s41591-018-0222-4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1107871640", 
              "https://doi.org/10.1038/s41591-018-0222-4"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2019-03-23", 
        "datePublishedReg": "2019-03-23", 
        "description": "AIMS/HYPOTHESIS: Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment.\nMETHODS: Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6\u00a0weeks. Inclusion criteria were men of age 18-35\u00a0years, BMI between 18.5\u00a0kg/m2 and 27.5\u00a0kg/m2, HbA1c\u2009<\u200939\u00a0mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2\u00a0months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1\u00a0g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit.\nRESULTS: Data from participants who completed visit 1 (n=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of Intestinibacter spp. and Clostridium spp., as well as an increased abundance of Escherichia/Shigella spp. and Bilophila wadsworthia. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects.\nCONCLUSIONS/INTERPRETATION: Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies.\nTRIAL REGISTRATION: Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050 FUNDING: This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1007/s00125-019-4848-7", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1001482", 
            "issn": [
              "0012-186X", 
              "1432-0428"
            ], 
            "name": "Diabetologia", 
            "type": "Periodical"
          }
        ], 
        "name": "Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study", 
        "pagination": "1-12", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "2b09959c4d7f2d4efead6c0a06a9d9a89d1d0450ff65721cc8407f1e1a7ccef4"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "30904939"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0006777"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/s00125-019-4848-7"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1112964833"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/s00125-019-4848-7", 
          "https://app.dimensions.ai/details/publication/pub.1112964833"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T12:57", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000365_0000000365/records_71677_00000002.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://link.springer.com/10.1007%2Fs00125-019-4848-7"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00125-019-4848-7'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00125-019-4848-7'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00125-019-4848-7'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00125-019-4848-7'


     

    This table displays all metadata directly associated to this object as RDF triples.

    267 TRIPLES      21 PREDICATES      64 URIs      18 LITERALS      7 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/s00125-019-4848-7 schema:about anzsrc-for:11
    2 anzsrc-for:1103
    3 schema:author Ncb66224019194331955663d270a9a9d9
    4 schema:citation sg:pub.10.1007/bf00280883
    5 sg:pub.10.1007/s10928-015-9436-y
    6 sg:pub.10.1038/nature11450
    7 sg:pub.10.1038/nature11808
    8 sg:pub.10.1038/nature12198
    9 sg:pub.10.1038/nature13270
    10 sg:pub.10.1038/nature15766
    11 sg:pub.10.1038/nm.3787
    12 sg:pub.10.1038/nm.4345
    13 sg:pub.10.1038/nmeth.3869
    14 sg:pub.10.1038/s41591-018-0222-4
    15 sg:pub.10.1186/s12864-017-4195-3
    16 https://app.dimensions.ai/details/publication/pub.1078621898
    17 https://doi.org/10.1016/s0002-9343(97)00254-4
    18 https://doi.org/10.1016/s0006-2952(99)00396-2
    19 https://doi.org/10.1017/s0007114516004086
    20 https://doi.org/10.1078/07232020260517625
    21 https://doi.org/10.1084/jem.20171965
    22 https://doi.org/10.1093/ajcn/85.5.1185
    23 https://doi.org/10.1111/dom.12811
    24 https://doi.org/10.1126/science.aad3369
    25 https://doi.org/10.1126/science.aad3503
    26 https://doi.org/10.1128/aem.00062-07
    27 https://doi.org/10.1128/mbio.00261-11
    28 https://doi.org/10.1136/gutjnl-2012-303839
    29 https://doi.org/10.1136/gutjnl-2014-307873
    30 https://doi.org/10.1136/gutjnl-2014-308778
    31 https://doi.org/10.1172/jci13505
    32 https://doi.org/10.1172/jci40671
    33 https://doi.org/10.1185/03007998409109558
    34 https://doi.org/10.1371/journal.pone.0009085
    35 https://doi.org/10.1371/journal.pone.0204317
    36 https://doi.org/10.2147/dmso.s43731
    37 https://doi.org/10.2337/dc13-2817
    38 https://doi.org/10.2337/dc15-0488
    39 https://doi.org/10.2337/dc16-1324
    40 https://doi.org/10.2337/diacare.15.6.755
    41 https://doi.org/10.3389/fmicb.2016.01706
    42 schema:datePublished 2019-03-23
    43 schema:datePublishedReg 2019-03-23
    44 schema:description AIMS/HYPOTHESIS: Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment. METHODS: Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6 weeks. Inclusion criteria were men of age 18-35 years, BMI between 18.5 kg/m2 and 27.5 kg/m2, HbA1c < 39 mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2 months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1 g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit. RESULTS: Data from participants who completed visit 1 (n=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of Intestinibacter spp. and Clostridium spp., as well as an increased abundance of Escherichia/Shigella spp. and Bilophila wadsworthia. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects. CONCLUSIONS/INTERPRETATION: Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies. TRIAL REGISTRATION: Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050 FUNDING: This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation.
    45 schema:genre research_article
    46 schema:inLanguage en
    47 schema:isAccessibleForFree false
    48 schema:isPartOf sg:journal.1001482
    49 schema:name Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study
    50 schema:pagination 1-12
    51 schema:productId N3182ae0373174411ac6bd7299843a93f
    52 N44e2e6c2601849e5aaccff62f686a927
    53 Na2cf6c11e4084639b5bb22d886984506
    54 Nb1bf0bd34f1445b6bed0d640eb6377c0
    55 Nc4daa2b1ccef488bb7dce057d84c4f9a
    56 schema:sameAs https://app.dimensions.ai/details/publication/pub.1112964833
    57 https://doi.org/10.1007/s00125-019-4848-7
    58 schema:sdDatePublished 2019-04-11T12:57
    59 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    60 schema:sdPublisher N67ea0549940c4daeb935a05bb45e715d
    61 schema:url https://link.springer.com/10.1007%2Fs00125-019-4848-7
    62 sgo:license sg:explorer/license/
    63 sgo:sdDataset articles
    64 rdf:type schema:ScholarlyArticle
    65 N09ba3c0a062d498684bba8df0da06840 schema:affiliation https://www.grid.ac/institutes/grid.452905.f
    66 schema:familyName Hansen
    67 schema:givenName Tue H.
    68 rdf:type schema:Person
    69 N0b982a72b58e46aabe1801fb89e6af23 rdf:first N14e1f99b93464ab08076e65bf06ed14d
    70 rdf:rest N61fbf89672aa4f47b2df651e9594e365
    71 N0c5385c0ec67483c8ee984d72ab42632 schema:affiliation https://www.grid.ac/institutes/grid.10825.3e
    72 schema:familyName Hansen
    73 schema:givenName Torben
    74 rdf:type schema:Person
    75 N14192cef92244a65a51cb2d6f9e69a86 rdf:first Nc8743469f62d49f9882191e5fd177c43
    76 rdf:rest N0b982a72b58e46aabe1801fb89e6af23
    77 N14a8edabdfd340e0b7b87937773b02ab rdf:first N5b5b582acc9c45d3b46c2a87f3ed6207
    78 rdf:rest Nc9bb5adf788945258d441f285bf00050
    79 N14e1f99b93464ab08076e65bf06ed14d schema:affiliation https://www.grid.ac/institutes/grid.5254.6
    80 schema:familyName Kern
    81 schema:givenName Timo
    82 rdf:type schema:Person
    83 N17ae61745f6a4f70a4037d55159e1c70 schema:affiliation https://www.grid.ac/institutes/grid.419658.7
    84 schema:familyName Vestergaard
    85 schema:givenName Henrik
    86 rdf:type schema:Person
    87 N1bb922945d924703b24a6148918984de rdf:first N4c79f348c0494c2a97d4c138385af32f
    88 rdf:rest N14a8edabdfd340e0b7b87937773b02ab
    89 N3182ae0373174411ac6bd7299843a93f schema:name dimensions_id
    90 schema:value pub.1112964833
    91 rdf:type schema:PropertyValue
    92 N35be0409193e46fe93609f3d61e94d01 rdf:first N09ba3c0a062d498684bba8df0da06840
    93 rdf:rest N8fa0f03e55de4eb4b85fb6b991f14bfe
    94 N44e2e6c2601849e5aaccff62f686a927 schema:name doi
    95 schema:value 10.1007/s00125-019-4848-7
    96 rdf:type schema:PropertyValue
    97 N4c79f348c0494c2a97d4c138385af32f schema:affiliation https://www.grid.ac/institutes/grid.10825.3e
    98 schema:familyName Brandslund
    99 schema:givenName Ivan
    100 rdf:type schema:Person
    101 N52676513def2465fa3850d70f19bb773 schema:affiliation https://www.grid.ac/institutes/grid.411702.1
    102 schema:familyName Allin
    103 schema:givenName Kristine H.
    104 rdf:type schema:Person
    105 N56731649e72444b3b1f46d15020848c1 schema:affiliation https://www.grid.ac/institutes/grid.5254.6
    106 schema:familyName Nielsen
    107 schema:givenName Trine
    108 rdf:type schema:Person
    109 N5b5b582acc9c45d3b46c2a87f3ed6207 schema:affiliation https://www.grid.ac/institutes/grid.10825.3e
    110 schema:familyName Jørgensen
    111 schema:givenName Niklas R.
    112 rdf:type schema:Person
    113 N61fbf89672aa4f47b2df651e9594e365 rdf:first N52676513def2465fa3850d70f19bb773
    114 rdf:rest N1bb922945d924703b24a6148918984de
    115 N67ea0549940c4daeb935a05bb45e715d schema:name Springer Nature - SN SciGraph project
    116 rdf:type schema:Organization
    117 N6b450a436ae24fc7b5fcd95bc5e8a994 schema:affiliation https://www.grid.ac/institutes/grid.5254.6
    118 schema:familyName Pedersen
    119 schema:givenName Oluf
    120 rdf:type schema:Person
    121 N8fa0f03e55de4eb4b85fb6b991f14bfe rdf:first N6b450a436ae24fc7b5fcd95bc5e8a994
    122 rdf:rest Nabe1933915aa4a1ba3f75bac4663b4eb
    123 N8fbae63ac3e847c3891d50d220b981eb rdf:first N0c5385c0ec67483c8ee984d72ab42632
    124 rdf:rest N35be0409193e46fe93609f3d61e94d01
    125 Na2cf6c11e4084639b5bb22d886984506 schema:name pubmed_id
    126 schema:value 30904939
    127 rdf:type schema:PropertyValue
    128 Nabe1933915aa4a1ba3f75bac4663b4eb rdf:first N56731649e72444b3b1f46d15020848c1
    129 rdf:rest rdf:nil
    130 Nb1bf0bd34f1445b6bed0d640eb6377c0 schema:name readcube_id
    131 schema:value 2b09959c4d7f2d4efead6c0a06a9d9a89d1d0450ff65721cc8407f1e1a7ccef4
    132 rdf:type schema:PropertyValue
    133 Nc4daa2b1ccef488bb7dce057d84c4f9a schema:name nlm_unique_id
    134 schema:value 0006777
    135 rdf:type schema:PropertyValue
    136 Nc8743469f62d49f9882191e5fd177c43 schema:affiliation https://www.grid.ac/institutes/grid.5254.6
    137 schema:familyName Thomsen
    138 schema:givenName Cæcilie W.
    139 rdf:type schema:Person
    140 Nc9bb5adf788945258d441f285bf00050 rdf:first N17ae61745f6a4f70a4037d55159e1c70
    141 rdf:rest N8fbae63ac3e847c3891d50d220b981eb
    142 Ncb66224019194331955663d270a9a9d9 rdf:first Ned3b935546a243ca99ceb360418d10cc
    143 rdf:rest N14192cef92244a65a51cb2d6f9e69a86
    144 Ned3b935546a243ca99ceb360418d10cc schema:affiliation https://www.grid.ac/institutes/grid.5254.6
    145 schema:familyName Bryrup
    146 schema:givenName Thomas
    147 rdf:type schema:Person
    148 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    149 schema:name Medical and Health Sciences
    150 rdf:type schema:DefinedTerm
    151 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
    152 schema:name Clinical Sciences
    153 rdf:type schema:DefinedTerm
    154 sg:journal.1001482 schema:issn 0012-186X
    155 1432-0428
    156 schema:name Diabetologia
    157 rdf:type schema:Periodical
    158 sg:pub.10.1007/bf00280883 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027902786
    159 https://doi.org/10.1007/bf00280883
    160 rdf:type schema:CreativeWork
    161 sg:pub.10.1007/s10928-015-9436-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1033261734
    162 https://doi.org/10.1007/s10928-015-9436-y
    163 rdf:type schema:CreativeWork
    164 sg:pub.10.1038/nature11450 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004546178
    165 https://doi.org/10.1038/nature11450
    166 rdf:type schema:CreativeWork
    167 sg:pub.10.1038/nature11808 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016730403
    168 https://doi.org/10.1038/nature11808
    169 rdf:type schema:CreativeWork
    170 sg:pub.10.1038/nature12198 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002791386
    171 https://doi.org/10.1038/nature12198
    172 rdf:type schema:CreativeWork
    173 sg:pub.10.1038/nature13270 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024050118
    174 https://doi.org/10.1038/nature13270
    175 rdf:type schema:CreativeWork
    176 sg:pub.10.1038/nature15766 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014535385
    177 https://doi.org/10.1038/nature15766
    178 rdf:type schema:CreativeWork
    179 sg:pub.10.1038/nm.3787 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005202989
    180 https://doi.org/10.1038/nm.3787
    181 rdf:type schema:CreativeWork
    182 sg:pub.10.1038/nm.4345 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085459595
    183 https://doi.org/10.1038/nm.4345
    184 rdf:type schema:CreativeWork
    185 sg:pub.10.1038/nmeth.3869 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016631324
    186 https://doi.org/10.1038/nmeth.3869
    187 rdf:type schema:CreativeWork
    188 sg:pub.10.1038/s41591-018-0222-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107871640
    189 https://doi.org/10.1038/s41591-018-0222-4
    190 rdf:type schema:CreativeWork
    191 sg:pub.10.1186/s12864-017-4195-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1092272577
    192 https://doi.org/10.1186/s12864-017-4195-3
    193 rdf:type schema:CreativeWork
    194 https://app.dimensions.ai/details/publication/pub.1078621898 schema:CreativeWork
    195 https://doi.org/10.1016/s0002-9343(97)00254-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005252023
    196 rdf:type schema:CreativeWork
    197 https://doi.org/10.1016/s0006-2952(99)00396-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028761556
    198 rdf:type schema:CreativeWork
    199 https://doi.org/10.1017/s0007114516004086 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008159895
    200 rdf:type schema:CreativeWork
    201 https://doi.org/10.1078/07232020260517625 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008890102
    202 rdf:type schema:CreativeWork
    203 https://doi.org/10.1084/jem.20171965 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100421130
    204 rdf:type schema:CreativeWork
    205 https://doi.org/10.1093/ajcn/85.5.1185 schema:sameAs https://app.dimensions.ai/details/publication/pub.1077415617
    206 rdf:type schema:CreativeWork
    207 https://doi.org/10.1111/dom.12811 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035154399
    208 rdf:type schema:CreativeWork
    209 https://doi.org/10.1126/science.aad3369 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049864477
    210 rdf:type schema:CreativeWork
    211 https://doi.org/10.1126/science.aad3503 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017663631
    212 rdf:type schema:CreativeWork
    213 https://doi.org/10.1128/aem.00062-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045980007
    214 rdf:type schema:CreativeWork
    215 https://doi.org/10.1128/mbio.00261-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017408208
    216 rdf:type schema:CreativeWork
    217 https://doi.org/10.1136/gutjnl-2012-303839 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009561639
    218 rdf:type schema:CreativeWork
    219 https://doi.org/10.1136/gutjnl-2014-307873 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019463103
    220 rdf:type schema:CreativeWork
    221 https://doi.org/10.1136/gutjnl-2014-308778 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016218646
    222 rdf:type schema:CreativeWork
    223 https://doi.org/10.1172/jci13505 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043705336
    224 rdf:type schema:CreativeWork
    225 https://doi.org/10.1172/jci40671 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012086379
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1185/03007998409109558 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034198355
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1371/journal.pone.0009085 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017487904
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1371/journal.pone.0204317 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107281380
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.2147/dmso.s43731 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037910058
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.2337/dc13-2817 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051706700
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.2337/dc15-0488 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016430875
    238 rdf:type schema:CreativeWork
    239 https://doi.org/10.2337/dc16-1324 schema:sameAs https://app.dimensions.ai/details/publication/pub.1070730310
    240 rdf:type schema:CreativeWork
    241 https://doi.org/10.2337/diacare.15.6.755 schema:sameAs https://app.dimensions.ai/details/publication/pub.1070745705
    242 rdf:type schema:CreativeWork
    243 https://doi.org/10.3389/fmicb.2016.01706 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016587504
    244 rdf:type schema:CreativeWork
    245 https://www.grid.ac/institutes/grid.10825.3e schema:alternateName University of Southern Denmark
    246 schema:name Department of Biochemistry and Immunology, Lillebaelt Hospital, Vejle, Denmark
    247 Dept of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
    248 Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
    249 Institute of Regional Health Research, University of Southern Denmark (SDU), Odense C, Denmark
    250 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark
    251 Odense Patient data Explorative Network (OPEN), Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
    252 rdf:type schema:Organization
    253 https://www.grid.ac/institutes/grid.411702.1 schema:alternateName Bispebjerg Hospital
    254 schema:name Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark
    255 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark
    256 rdf:type schema:Organization
    257 https://www.grid.ac/institutes/grid.419658.7 schema:alternateName Steno Diabetes Center
    258 schema:name Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark
    259 Steno Diabetes Center Copenhagen, Gentofte, Denmark
    260 rdf:type schema:Organization
    261 https://www.grid.ac/institutes/grid.452905.f schema:alternateName Slagelse Hospital
    262 schema:name Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark
    263 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark
    264 rdf:type schema:Organization
    265 https://www.grid.ac/institutes/grid.5254.6 schema:alternateName University of Copenhagen
    266 schema:name Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, Denmark
    267 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...