title: Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study.
abstract: OBJECTIVE
  The role of biomarkers of subclinical inflammation in the early deterioration of glycaemia before type 2 diabetes is largely unknown. We hypothesised that increased levels of circulating proinflammatory biomarkers and decreased circulating adiponectin would be associated with 7 year increases of HbA(1c) in non-diabetic individuals.
  
  
  METHODS
  This study was based on individuals who participated in the prospective Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and the 7 year follow-up KORA F4 (2006-2008) survey. Individuals with type 2 diabetes at baseline or with a diagnosis of diabetes in the period between both surveys were excluded, which left a sample of 850 men and women. Multivariable linear regression analyses were performed to assess associations among baseline values of leucocyte count and levels of acute-phase proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and fibrinogen), IL-6 and adiponectin with changes in HbA1c between baseline and follow-up.
  
  
  RESULTS
  A high leucocyte count and high hsCRP, SAA and IL-6 levels were positively associated with changes in HbA(1c) after adjusting for age, sex, lifestyle factors and baseline HbA(1c). In contrast, the adiponectin level was inversely associated with changes in HbA(1c) (p value between <0.0001 and 0.020). The associations of leucocyte count and levels of hsCRP and SAA with HbA(1c) changes remained significant after additional adjustment for waist circumference and circulating lipids at baseline and for the 7 year change in waist circumference (p value between 0.004 and 0.045).
  
  
  CONCLUSIONS
  An elevated leucocyte count and elevated hsCRP and SAA were associated with early deterioration of glycaemia before the diagnosis of type 2 diabetes. These associations were largely independent of baseline abdominal adiposity and increases in waist circumference.
authors.affiliation: Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Klüppelholz
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm Medical Center, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: de Las Heras Gala
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Huth
authors.affiliation: Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|Institute for Statistics in Medicine, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Giani
authors.affiliation: Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.|Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden.|Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.affiliation: Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany.|German Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: Institute of Epidemiology II, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.|German Center for Diabetes Research, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de.|German Center for Diabetes Research, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose; D002097:C-Reactive Protein / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: C499918:ADIPOQ protein, human; D000209:Acute-Phase Proteins; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D005340:Fibrinogen; D002097:C-Reactive Protein
keywords: Adiponectin; Cohort study; Cytokines; Glycaemia; HbA1c; Inflammation; Type 2 diabetes