Prospective Evaluation of B-type Natriuretic Peptide Concentrations and the Risk of Type 2 Diabetes in Women

被引:28
作者
Everett, Brendan M. [1 ,2 ]
Cook, Nancy R. [1 ]
Chasman, Daniel I. [1 ]
Magnone, Maria C. [3 ]
Bobadilla, Maria [3 ]
Rifai, Nader [4 ]
Ridker, Paul M. [1 ,2 ]
Pradhan, Aruna D. [1 ,5 ]
机构
[1] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA
[3] F Hoffmann La Roche & Cie AG, Pharma Metab & Vasc Dis, Basel, Switzerland
[4] Childrens Hosp, Dept Pathol, Div Lab Med, Boston, MA 02115 USA
[5] VA Boston Med Ctr, Div Cardiovasc Med, Boston, MA USA
关键词
CASE-COHORT DESIGN; ASSOCIATION; DIAGNOSIS; GENE; PREVENTION; MELLITUS; DISEASE; MAP;
D O I
10.1373/clinchem.2012.194167
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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 [beta (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. (C) 2012 American Association for Clinical Chemistry
引用
收藏
页码:557 / 565
页数:9
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