title: Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study.
abstract: OBJECTIVE
  Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional.
  
  
  METHODS
  We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers.
  
  
  RESULTS
  Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin.
  
  
  CONCLUSIONS
  Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.
authors.affiliation: Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany christian.herder@ddz.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: Steno Diabetes CenterGentofte, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Færch
authors.affiliation: Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen-Kirberg
authors.affiliation: Institute of Cardiovascular and Medical SciencesUniversity of Glasgow, Glasgow, UK.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Lowe
authors.affiliation: Department of Epidemiology and Public HealthUniversity College London, London, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Haapakoski
authors.affiliation: Department of Public HealthAarhus University, Aarhus, Denmark Danish Diabetes AcademyOdense, Denmark.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.affiliation: Department of Epidemiology and Public HealthUniversity College London, London, UK.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brunner
authors.affiliation: Institute for Clinical DiabetologyGerman Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes ResearchMünchen-Neuherberg, Germany Department of Endocrinology and DiabetologyMedical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Department of Epidemiology and Public HealthUniversity College London, London, UK First Department of MedicineFaculty of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Tabák
authors.affiliation: Department of Epidemiology and Public HealthUniversity College London, London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
authors.affiliation: Steno Diabetes CenterGentofte, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Vistisen
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D002097:C-Reactive Protein