title: Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort.
abstract: Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus.
  
  
  
  This prospective study included 1014 individuals at high risk of type 2 diabetes mellitus participating in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment In PeOple with ScreeN-detected Diabetes in Primary Care (ADDITION-Europe trial) baseline examination in 2001-2006 and follow-up examination (ADDITION-Progression [ADDITION-PRO]) in 2009-2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2 h glucose, fasting insulin, HOMA-IR and HOMA-β were assessed using a mixed-effects model.
  
  
  
  A doubling of sCD163 concentration was positively associated with changes in fasting insulin (β = 1.078 per year, 95% CI 0.454, 1.702) and HOMA-β (β = 1.313 per year, 95% CI 0.537, 2.089), and a doubling of CRP concentration was positively associated with HbA 1c (β = 0.004 per year, 95% CI 0.001, 0.007) and fasting insulin (β = 0.267 per year, 95% CI 0.029, 0.504) after adjustment for age and sex. A doubling of adiponectin was inversely associated with changes in fasting glucose (β = −0.017 per year, 95% CI −0.028, −0.005), 2 h glucose (β = −0.063 per year, 95% CI −0.107, −0.019), fasting insulin (β = −1.558 per year, 95% CI −2.020, −1.096), HOMA-IR (β = −0.040 per year, 95% CI −0.062, −0.019) and HOMA-β (β = −1.009 per year, 95% CI −1.589, −0.429) after adjustment for age and sex. The associations were robust to adjustment for baseline waist circumference and smoking. Adjustment for CRP did not change the associations for sCD163 or adiponectin.
  
  
  
  Our findings indicate that mechanisms related to inflammation, including macrophage activation and adipocyte metabolism, may play a role in changes in glucose homeostasis in individuals at high risk of type 2 diabetes mellitus.
authors.affiliation: Section of General Practice, Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000, Aarhus, Denmark. p.deichgraeber@ph.au.dk.
authors.forename: Pia
authors.initials: P
authors.lastname: Deichgræber
authors.affiliation: Department of Public Health, Aarhus University, Aarhus, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Section of Health Promotion and Health Services, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Mette V
authors.initials: MV
authors.lastname: Skriver
authors.affiliation: Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Richelsen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.|National Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Marit E
authors.initials: ME
authors.lastname: Jørgensen
authors.affiliation: Danish Diabetes Academy, Odense, Denmark.|Steno Diabetes Center, Gentofte, Denmark.|Research Centre for Prevention and Health, Centre for Health, Rigshospitalet-Glostrup, Denmark.
authors.forename: Nanna B
authors.initials: NB
authors.lastname: Johansen
authors.affiliation: Section of General Practice, Department of Public Health, Aarhus University, Bartholins Allé 2, DK-8000, Aarhus, Denmark.
authors.forename: Annelli
authors.initials: A
authors.lastname: Sandbæk
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000097:blood*; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D000098902:CD163 Antigen
chemical_list: D052242:Adiponectin; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D000098902:CD163 Antigen; D007328:Insulin; D011956:Receptors, Cell Surface; D002097:C-Reactive Protein; D002784:Cholesterol
keywords: Adiponectin; C-reactive protein; Glycaemia; Inflammation; Insulin resistance; Insulin secretion; Prospective study; Type 2 diabetes mellitus; sCD163