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: Weused 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 (NTproBNP) 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/m2, P < 0.001) and lower baseline median (interquartile range) NTproBNP 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. © 2012 American Association for Clinical Chemistry.