title: Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27).
abstract: C-reactive protein (CRP), procalcitonin (PCT) and pro-adrenomedullin (MR-proADM) are inflammation markers associated with long-term mortality risk. We compared the associations and predictive capacities of CRP, PCT and MR-proADM with cardiovascular and all-cause mortality in patients with type 2 diabetes.
  
  
  
  This study included primary care treated patients with type 2 diabetes participating in the ZODIAC cohort study. A total of 1005 out of 1688 patients (60%) had complete baseline variables. Baseline CRP, PCT and MR-proADM were assessed in relation to cardiovascular and all-cause mortality with Cox proportional hazard analyses. Hazard Ratios (HR) were adjusted for age, gender, BMI, smoking, systolic blood pressure, cholesterol-HDL ratio, duration of diabetes, HbA1c, history of cardiovascular diseases, albumin-creatinine ratio and creatinine. Risk prediction capabilities were assessed with Harrell's C statistics and proportion of explained variance (R(2)).
  
  
  
  After a median follow-up of 11 years, 472 (47%) of 1005 patients had died. The likelihood ratio test showed that CRP and MR-proADM significantly improved prediction in cardiovascular mortality [HRs 1.20 (95%CI 1.09-1.33) and 1.56 (95%CI 1.06-2.30)] and in all-cause mortality [HRs 1.10 (95%CI: 1.03-1.18) and 1.31 (95%CI 1.02-1.69)]. Harrell's C values and R(2) measures showed slightly improved discrimination for cardiovascular mortality in patients without macrovascular disease (C: 0.80 to 0.81; R(2): 0.50 to 0.52) and MR-proADM (C: 0.80 to 0.82; R(2): 0.50 to 0.52).
  
  
  
  CRP and MR-proADM, but not PCT, were independently associated with cardiovascular and all-cause mortality. In patients without macrovascular diseases, CRP and MR-proADM slightly improved discrimination, in absolute sense, of patients at risk for cardiovascular mortality.
authors.affiliation: Langerhans Medical Research Institute, Zwolle, The Netherlands; Department of Internal Medicine, Gelre Hospital, Apeldoorn, The Netherlands. Electronic address: g.w.d.landman@isala.nl.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.affiliation: Langerhans Medical Research Institute, Zwolle, The Netherlands; Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
authors.affiliation: Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Diabetes Research Centre, Isala Hospital, Zwolle, The Netherlands.
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.affiliation: Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Leiden University Medical Center, The Netherlands.
authors.forename: Geert H
authors.initials: GH
authors.lastname: Groeneveld
authors.affiliation: Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Diabetes Research Centre, Isala Hospital, Zwolle, The Netherlands.
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.affiliation: Langerhans Medical Research Institute, Zwolle, The Netherlands.
authors.forename: Kornelis J J
authors.initials: KJ
authors.lastname: van Hateren
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000401:mortality; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011320:Primary Health Care; D016016:Proportional Hazards Models; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: Biomarker; Inflammation; Mortality; Prediction; Type 2 diabetes