title: Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy-a prospective follow--up study.
abstract: OBJECTIVE
  Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohort of Type 1 diabetic patients.
  
  
  METHODS
  In a prospective observational follow-up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0-10.3) years. PAPP-A was determined at baseline.
  
  
  RESULTS
  In patients with diabetic nephropathy, plasma PAPP-A was elevated 3.6 (0.4-51.1) mIU/l [median (range)] vs. 2.1 (0.4-46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP-A threshold of 10 mIU/l has been suggested. Thirty-seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP-A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP-A was above the threshold 2.1 (95% CI 1.13-3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP-A was significantly predictive of all-cause mortality [P = 0.008; 2.43 (1.26-4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP-A for all-cause mortality was attenuated (P = 0.064).
  
  
  CONCLUSIONS
  We find PAPP-A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. ansa@steno.dk
authors.forename: A S
authors.initials: AS
authors.lastname: Astrup
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.forename: P R
authors.initials: PR
authors.lastname: Hansen
authors.forename: H-H
authors.initials: HH
authors.lastname: Parving
authors.forename: P
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000401:mortality; D003928:Diabetic Nephropathies / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*
chemical_list: D011266:Pregnancy-Associated Plasma Protein-A