Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person ...variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies.
Women in the Nurses' Health Study and Nurses' Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid.
Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results.
Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.
Blood soluble E-selectin (sE-selectin) levels have been related to various conditions such as type 2 diabetes. We performed a genome-wide association study among women of European ancestry from the ...Nurses' Health Study, and identified genome-wide significant associations between a cluster of markers at the ABO locus (9q34) and plasma sE-selectin concentration. The strongest association was with rs651007, which explained ∼9.71% of the variation in sE-selectin concentrations. SNP rs651007 was also nominally associated with soluble intracellular cell adhesion molecule-1 (sICAM-1) (P = 0.026) and TNF-R2 levels (P = 0.018), independent of sE-selectin. In addition, the genetic-inferred ABO blood group genotypes were associated with sE-selectin concentrations (P = 3.55 × 10−47). Moreover, we found that the genetic-inferred blood group B was associated with a decreased risk (OR = 0.44, 0.27–0.70) of type 2 diabetes compared with blood group O, adjusting for sE-selectin, sICAM-1, TNF-R2 and other covariates. Our findings indicate that the genetic variants at ABO locus affect plasma sE-selectin levels and diabetes risk. The genetic associations with diabetes risk were independent of sE-selectin levels.
Healthful dietary patterns have been associated with lower risks of type 2 diabetes and coronary artery disease, but their relations with intermediate markers of cardiometabolic and endocrine health ...are less established.
We evaluated the Dietary Approaches to Stop Hypertension (DASH), the alternate Mediterranean diet (aMED), and the Alternate Healthy Eating Index (aHEI) diet-quality scores with cardiometabolic and endocrine plasma biomarkers in US women.
The trial was a cross-sectional analysis of 775 healthy women in the Women's Lifestyle Validation Study that was conducted within the NHS (Nurses' Health Study) and NHS II longitudinal cohorts. Multiple linear regression models adjusted for potential confounders were used to estimate associations between quartiles of dietary pattern-adherence scores that were derived from a food-frequency questionnaire and plasma biomarker concentrations that were collected simultaneously.
In multivariable models in which highest and lowest quartiles of dietary pattern scores were compared, 1) DASH was significantly associated with higher concentrations of high-density lipoprotein (9%) and sex-hormone binding globulin (SHBG) (21%), and lower concentrations of leptin (28%), triglycerides (19%), and C-peptide (4%) (all P-trend ≤ 0.04); 2) the aMED was associated with 19% higher SHBG and 16% lower triglycerides (P-trend = 0.02 and 0.003, respectively); and 3) the aHEI was associated with significantly higher concentrations of insulin (16%) and SHBG (19%) and lower concentrations of leptin (18%) (all P-trend ≤ 0.02). Further adjustment for body mass index (BMI) attenuated these associations but remained significant for 1) DASH with leptin and triglycerides and 2) the aMED with triglycerides (all P-trend ≤ 0.03).
Adherence to healthful dietary patterns is associated with favorable concentrations of many cardiometabolic and endocrine biomarkers. These relations are mediated in part by BMI.
CONTEXT Adiponectin, a recently discovered adipocyte-derived peptide, is involved
in the regulation of insulin sensitivity and lipid oxidation and, purportedly,
in the development of atherosclerosis ...and coronary heart disease in humans. OBJECTIVE To assess prospectively whether plasma adiponectin concentrations are
associated with risk of myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS Nested case-control study among 18 225 male participants of the
Health Professionals Follow-up Study aged 40 to 75 years who were free of
diagnosed cardiovascular disease at the time of blood draw (1993-1995). During
6 years of follow-up through January 31, 2000, 266 men subsequently developed
nonfatal MI or fatal coronary heart disease. Using risk set sampling, controls
were selected in a 2:1 ratio matched for age, date of blood draw, and smoking
status (n = 532). MAIN OUTCOME MEASURE Incidence of nonfatal MI and fatal coronary heart disease by adiponectin
level. RESULTS After adjustment for matched variables, participants in the highest
compared with the lowest quintile of adiponectin levels had a significantly
decreased risk of MI (relative risk RR, 0.39; 95% confidence interval CI,
0.23-0.64; P for trend <.001). Additional adjustment
for family history of MI, body mass index, alcohol consumption, physical activity,
and history of diabetes and hypertension did not substantively affect this
relationship (RR, 0.41; 95% CI, 0.24-0.70; P for
trend <.001). Further adjustment for hemoglobin A1c or C-reactive
protein levels also had little impact, but additional adjustment for low-
and high-density lipoprotein cholesterol levels modestly attenuated this association
(RR, 0.56; 95% CI, 0.32-0.99; P for trend = .02). CONCLUSIONS High plasma adiponectin concentrations are associated with lower risk
of MI in men. This relationship can be only partly explained by differences
in blood lipids and is independent of inflammation and glycemic status.
Maternal famine exposure has been associated with higher blood pressure in the offspring. The aim of the present study was to examine the associations of early life exposure to the 1959-1961 Chinese ...famine with the risk of hypertension in later life, and to examine whether a nutritional 'rich' environment in later life modifies this association.
We used data of 7874 adults born between 1954 and 1964 from the 2002 China National Nutrition and Health Survey. Excess death rate was used to determine the severity of the famine.
In severely affected famine areas, as compared to adults who were not exposed to famine, those exposed during fetal life had a significantly higher SBP SBP difference 2.2 mmHg, 95% confidence interval (CI) 1.3-3.0, P < 0.0001, DBP (DBP difference 0.9 mmHg, 95% CI 0.3-1.5, P = 0.003) and a marginally higher risk of hypertension (odds ratio 1.88, 95% CI 1.00-3.53, P = 0.05), after adjustment of age, sex, socioeconomic status, lifestyle, dietary factors and family history of hypertension, which was not observed in less severely affected famine areas (P for interaction was 0.08 for SBP, 0.03 for DBP and 0.03 for hypertension). These associations were more pronounced in participants who had a western dietary pattern or who were overweight as adult.
Our results suggest that fetal famine exposure is associated with higher blood pressure and an increased risk of hypertension in adulthood. These associations are stronger in participants who have a western dietary pattern or who are overweight as adults.
IGF-I shares structural homology and in vitro metabolic activity with insulin. Laboratory models suggest that IGF-I and its binding proteins IGFBP-1 and IGFBP-2 have potentially beneficial effects on ...diabetes risk, whereas IGFBP-3 may have adverse effects. We therefore conducted a prospective nested case-control investigation of incident diabetes (n = 742 case subjects matched 1:1 to control subjects) and its associations with IGF-axis protein levels in the Nurses' Health Study, a cohort of middle-aged women. The median time to diabetes was 9 years. Statistical analyses were adjusted for multiple risk factors, including insulin and C-reactive protein. Diabetes risk was fivefold lower among women with baseline IGFBP-2 levels in the top versus bottom quintile (odds ratio OR(q5-q1) = 0.17 95% CI 0.08-0.35; P trend < 0.0001) and was also negatively associated with IGFBP-1 levels (OR(q5-q1) = 0.37 0.18-0.73; P trend = 0.0009). IGFBP-3 was positively associated with diabetes (OR(q5-q1) = 2.05 1.20-3.51; P trend = 0.002). Diabetes was not associated with total IGF-I levels, but free IGF-I and diabetes had a significant association that varied (P interaction = 0.003) by insulin levels above the median (OR(q5-q1) = 0.48 0.26-0.90; P trend = 0.0001) versus below the median (OR(q5-q1) = 2.52 1.05-6.06; P trend < 0.05). Thus, this prospective study found strong associations of incident diabetes with baseline levels of three IGFBPs and free IGF-I, consistent with hypotheses that the IGF axis might influence diabetes risk.
CONTEXT Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus
but may also precede development of diabetes. OBJECTIVE To determine whether elevated plasma levels of biomarkers ...reflecting
endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 ICAM-1;
and vascular cell adhesion molecule 1 VCAM-1) predict development of type
2 diabetes in initially nondiabetic women. DESIGN AND SETTING Prospective, nested case-control study within the Nurses' Health Study,
an ongoing US study initiated in 1976. PARTICIPANTS Of 121 700 women initially enrolled, 32 826 provided blood
samples in 1989-1990; of those free of diabetes, cardiovascular disease, or
cancer at baseline, 737 developed incident diabetes by 2000. Controls (n =
785) were selected according to matched age, fasting status, and race. MAIN OUTCOME MEASURE Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels
of E-selectin, ICAM-1, and VCAM-1. RESULTS Baseline median levels of the biomarkers were significantly higher among
cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs
247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL all P values
≤.004). Elevated E-selectin and ICAM-1 levels predicted incident diabetes
in logistic regression models conditioned on matching criteria and adjusted
for body mass index (BMI), family history of diabetes, smoking, diet score,
alcohol intake, activity index, and postmenopausal hormone use. The adjusted
relative risks for incident diabetes in the top quintile vs the bottom quintiles
were 5.43 for E-selectin (95% confidence interval CI, 3.47-8.50), 3.56 for
ICAM-1 (95% CI, 2.28-5.58), and 1.12 for VCAM-1 (95% CI, 0.76-1.66). Adjustment
for waist circumference instead of BMI or further adjustment for baseline
levels of C-reactive protein, fasting insulin, and hemoglobin A1c or
exclusion of cases diagnosed during the first 4 years of follow-up did not
alter these associations. CONCLUSION Endothelial dysfunction predicts type 2 diabetes in women independent
of other known risk factors, including obesity and subclinical inflammation.
Few studies have examined the contribution of major dietary patterns to markers of systemic inflammation. This study was conducted to evaluate the association of major dietary patterns with markers ...of systemic inflammation among Iranian women. In a cross-sectional study of 486 healthy women aged 40-60 y, we assessed usual dietary intakes by means of an FFQ. Dietary patterns were identified by factor analysis. Anthropometric measurements were made and blood samples from fasting were taken for measuring inflammatory markers. The healthy pattern (high in fruits, vegetables, tomato, poultry, legumes, tea, fruit juices, and whole grains) was inversely related to plasma concentrations of C-reactive protein (CRP) (beta = -0.09, P < 0.001), E-selectin (beta = -0.07, P < 0.05), and soluble vascular cell adhesion molecule-1 (sVCAM-1) (beta = -0.08, P < 0.001) after control for potential confounders; with further adjustment for BMI and waist circumference (WC), the associations remained significant for CRP (beta = -0.05, P < 0.05) and sVCAM-1 (beta = -0.04, P < 0.05). In contrast, the western pattern score (high in refined grains, red meat, butter, processed meat, high-fat dairy, sweets and desserts, pizza, potato, eggs, hydrogenated fats, and soft drinks) was positively related to CRP (beta = 0.08, P < 0.001), serum amyloid A (SAA) (beta = 0.11, P < 0.05), IL-6 (beta = 0.09, P < 0.001), soluble intercellular adhesion molecule-1 (beta = 0.05, P < 0.05), and sVCAM-1 concentrations (beta = 0.07, P < 0.05). However, after additional control for BMI and WC, the associations remained significant only for SAA (beta = 0.06, P < 0.05) and IL-6 (beta = 0.07, P < 0.001). The traditional dietary pattern (high in refined grains, potato, tea, whole grains, hydrogenated fats, legumes, and casserole) was positively associated with the plasma IL-6 concentration (beta = 0.04, P < 0.05) when we controlled for confounders including BMI and WC. The findings suggest an independent association between major dietary patterns and plasma concentrations of markers of inflammation.
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