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Publications (3)26.41 Total impact

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    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.
    Clinical Chemistry 01/2013; 59(3). DOI:10.1373/clinchem.2012.194167 · 7.91 Impact Factor
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    ABSTRACT: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that is increased in obesity and established type 2 diabetes. We assessed whether GDF-15 can predict future insulin resistance and impaired glucose control in obese nondiabetic individuals. Plasma GDF-15 concentrations were measured with an automated electrochemiluminescent immunoassay at baseline and after 4 years in 496 obese nondiabetic individuals (52% men, median age 48 years, median body mass index (BMI) 37.6 kg/m(2)) enrolled in the XENical in the prevention of Diabetes in Obese subjects (XENDOS) trial. THE MEDIAN GDF-15 CONCENTRATION AT BASELINE WAS 869NG/L (INTERQUARTILE RANGE 7231064NG/L). GDF-15 WAS RELATED TO BODY WEIGHT, BMI, WAIST-TO-HIP RATIO, AND INSULIN RESISTANCE (HOMEOSTASIS MODEL ASSESSMENT OF INSULIN RESISTANCE (HOMA-IR)) (ALL P0.01). CHANGES IN GDF-15 FROM BASELINE TO 4 YEARS WERE RELATED TO CHANGES IN BODY WEIGHT, BMI, WAIST-TO-HIP RATIO, AND HOMA-IR (ALL P0.05). BASELINE GDF-15 WAS ASSOCIATED WITH THE RISK TO HAVE PREDIABETES OR DIABETES AT 4 YEARS BY UNIVARIATE ANALYSIS (ODDS RATIO (OR) FOR 1 UNIT INCREASE IN LN GDF-15, 3.2; 95% CONFIDENCE INTERVAL (CI): 1.7-6.1; P<0.001), and after multivariate adjustment for age, gender, treatment allocation (orlistat vs placebo), BMI, waist-to-hip ratio, and glucose control at baseline (OR 2.2; 95% CI: 1.1-4.7; P=0.026). Similarly, baseline GDF-15 was independently associated with HOMA-IR at 4 years (P=0.024). This first longitudinal study of GDF-15 in a large cohort of obese individuals indicates that GDF-15 is related to abdominal obesity and insulin resistance and independently associated with future insulin resistance and abnormal glucose control.
    European Journal of Endocrinology 08/2012; 167(5):671-8. DOI:10.1530/EJE-12-0466 · 4.07 Impact Factor
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    ABSTRACT: Very low levels of cardiac troponin T are associated with an increased risk of cardiovascular death in patients with stable chronic coronary disease. Whether high-sensitivity cardiac troponin T levels are associated with adverse cardiovascular outcomes in individuals without cardiovascular disease (CVD) has not been well studied. Using 2 complementary study designs, we evaluated the relationship between baseline cardiac troponin and incident CVD events among diabetic and nondiabetic participants in the Women's Health Study (median follow-up, 12.3 years). All diabetic women with blood specimens were included in a cohort study (n=512 diabetic women, n=65 events), and nondiabetic women were sampled for inclusion in a case-cohort analysis (n=564 comprising the subcohort, n=479 events). High-sensitivity cardiac troponin T was detectable (≥ 0.003 μg/L) in 45.5% of diabetic women and 30.3% of nondiabetic women (P<0.0001). In models adjusted for traditional risk factors and hemoglobin A(1c), detectable high-sensitivity cardiac troponin T was associated with subsequent CVD (myocardial infarction, stroke, cardiovascular death) in diabetic women (adjusted hazard ratio, 1.79; 95% confidence interval, 1.04 to 3.07, P=0.036) but not nondiabetic women (adjusted hazard ratio, 1.13; 95% confidence interval, 0.82 to 1.55; P=0.46). Further adjustment for amino-terminal pro-B-type natriuretic peptide and estimated renal function did not substantially alter this relationship among diabetic women (hazard ratio, 1.76; 95% confidence interval, 1.00 to 3.08; P=0.0499), which appeared to be driven by a 3-fold increase in CVD death that was not observed in nondiabetic women. Very low but detectable levels of cardiac troponin T are associated with total CVD and CVD death in women with diabetes mellitus. Among healthy nondiabetic women, detectable compared with undetectable troponin was not associated with CVD events.
    Circulation 06/2011; 123(24):2811-8. DOI:10.1161/CIRCULATIONAHA.110.009928 · 14.43 Impact Factor