title: Prospective evaluation of B-type natriuretic peptide concentrations and the risk of type 2 diabetes in women.
abstract: BACKGROUND
  Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting.
  
  
  METHODS
  We used a prospective case-cohort approach (n = 491 T2DM cases, n = 561 reference subcohort) within the Women's Health Study to evaluate baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and the risk of incident T2DM. We also tested for associations between 4 common variants in the natriuretic peptide A and B genes (NPPA and NPPB) and NT-proBNP concentrations (n = 458) and incident T2DM (n = 1372 cases among 22 607 women).
  
  
  RESULTS
  Case subjects had higher median baseline body mass index (29.4 vs 25.0 kg/m(2), P < 0.001) and lower baseline median (interquartile range) NT-proBNP concentrations [46.8 ng/L (26.1-83.2) vs 66.7 ng/L (39.3-124.7), P < 0.001]. In proportional hazards models adjusting for established diabetes risk factors, women in the highest quartile of baseline NT-proBNP concentration (≥ 117.4 ng/L) had a 49% reduction in risk of T2DM [hazard ratio (HR) 0.51, 0.30-0.86, P = 0.01] relative to those in the lowest quartile. Two of the 4 tested variants in NPPA and NPPB (rs632793, rs198389) were associated with increased NT-proBNP concentrations and reduced risk of T2DM. For example, each copy of the minor allele of rs632793 was associated with increased NT-proBNP [β (SE) = 0.201 (0.063), P < 0.01] and decreased T2DM risk (HR 0.91, 0.84-0.989, P = 0.026).
  
  
  CONCLUSIONS
  NT-proBNP concentrations that are high, but still within the reference interval, associate with reduced risk of incident diabetes in women and support a favorable role for natriuretic peptides in the prevention of T2DM.
authors.affiliation: Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Everett
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Cook
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Maria C
authors.initials: MC
authors.lastname: Magnone
authors.forename: Maria
authors.initials: M
authors.lastname: Bobadilla
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Aruna D
authors.initials: AD
authors.lastname: Pradhan
mesh_terms: D009320:Atrial Natriuretic Factor / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk
chemical_list: C472955:NPPA protein, human; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor