title: Midregional fragment of proadrenomedullin, new-onset albuminuria, and cardiovascular and all-cause mortality in patients with type 2 diabetes (ZODIAC-30).
abstract: OBJECTIVE
  The midregional fragment of proadrenomedullin (MR-proADM) is a marker of endothelial dysfunction and has been associated with a variety of diseases. Our aim was to investigate whether MR-proADM is associated with new-onset albuminuria and cardiovascular (CV) and all-cause mortality in patients with type 2 diabetes treated in primary care.
  
  
  METHODS
  Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses were used to assess the relation of baseline MR-proADM with new-onset albuminuria and CV and all-cause mortality. Risk prediction capabilities of MR-proADM for new-onset albuminuria and CV and all-cause mortality were assessed with Harrell's C and the integrated discrimination improvement.
  
  
  RESULTS
  In 1,243 patients (mean age 67 [±12] years), the median follow-up was 5.6 years (interquartile range 3.1-10.1); 388 (31%) patients died, with 168 (12%) CV deaths. Log2 MR-proADM was associated with CV (hazard ratio 1.96 [95% CI 1.27-3.01]) and all-cause mortality (1.78 [1.34-2.36]) after adjusting for age, sex, BMI, smoking, systolic blood pressure, cholesterol-to-HDL ratio, duration of diabetes, HbA1c, ACE inhibitor/angiotensin receptor blocker, history of CV diseases, log serum creatinine, and log albumin-to-creatinine ratio. MR-proADM slightly improved mortality risk prediction. The age- and sex-adjusted, but not multivariate-adjusted, MR-proADM levels were associated with new-onset albuminuria.
  
  
  CONCLUSIONS
  MR-proADM was associated with CV and all-cause mortality in patients with type 2 diabetes after a median follow-up of 5.6 years. There was no independent relationship with new-onset albuminuria. In the availability of an extensive set of risk factors, there was little added effect of MR-proADM in risk prediction of CV and all-cause mortality.
authors.affiliation: Corresponding author: Gijs W.D. Landman, g.w.d.landman@isala.nl.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.forename: Peter R
authors.initials: PR
authors.lastname: van Dijk
authors.forename: Iefke
authors.initials: I
authors.lastname: Drion
authors.forename: Kornelis J J
authors.initials: KJ
authors.lastname: van Hateren
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.forename: Rijk O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
mesh_terms: D053607:Adrenomedullin / Q000097:blood* / Q000737:chemistry; D000368:Aged; D000419:Albuminuria / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood* / Q000737:chemistry; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin