Danxia Yu

A Marker of Endotoxemia Is Associated With Obesity and Related Metabolic Disorders in Apparently Healthy Chinese

OBJECTIVE Elevated lipopolysaccharide-binding protein (LBP), a marker of subclinical endotoxemia, may be involved in the pathogenesis of obesity and metabolic risk. We aimed to investigate the association between plasma LBP and metabolic disorders in apparently healthy Chinese. RESEARCH DESIGN AND METHODS A population-based study including 559 overweight/obese (BMI ≥24.0 kg/m2) and 500 normal-weight (18.0 ≤ BMI <24.0 kg/m2) subjects aged 35–54 years was conducted in Shanghai, China. Fasting plasma glucose, lipid profile, LBP, high-sensitivity C-reactive protein, interleukin-6, high-molecular-weight (HMW) adiponectin, leptin, hepatic enzymes, and body composition were measured. Metabolic syndrome was defined by the updated National Cholesterol Education Program Adult Treatment Panel III criterion for Asian Americans. RESULTS LBP levels were significantly higher in overweight/obese individuals than in normal-weight individuals (geometric mean 27.6 [95% CI 25.2–30.3] vs. 10.0 [9.1–11.1] μg/ml; P < 0.001). After multiple adjustments including BMI, the odds ratios were 3.54 (95% CI 2.05–6.09) and 5.53 (95% CI 2.64–11.59) for metabolic syndrome and type 2 diabetes, respectively, comparing the highest with the lowest LBP quartile. Further adjustments for inflammatory markers almost abolished the significant association of LBP with metabolic syndrome but not that with type 2 diabetes, and controlling for adipokines and hepatic enzymes did not substantially alter the results. CONCLUSIONS Elevated circulating LBP was associated with obesity, metabolic syndrome, and type 2 diabetes in apparently healthy Chinese. These findings suggested a role of lipopolysaccharide via initiation of innate immune mechanism(s) in metabolic disorders. Prospective studies are needed to confirm these results.

Meta-analysis of the effects of flaxseed interventions on blood lipids

BACKGROUND Several clinical trials have investigated the effects of flaxseed and flaxseed-derived products (flaxseed oil or lignans) on blood lipids; however, the findings have been inconsistent. OBJECTIVE We aimed to identify and quantify the effectiveness of flaxseed and its derivatives on blood lipid profiles. DESIGN A comprehensive literature search was performed on the basis of English reports of randomized controlled trials of flaxseed or its derivatives on lipid profiles in adults, which were published from January 1990 to October 2008. Attempts also were made to access unpublished data. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted. RESULTS Twenty-eight studies were included. Flaxseed interventions reduced total and LDL cholesterol by 0.10 mmol/L (95% CI: -0.20, 0.00 mmol/L) and 0.08 mmol/L (95% CI: -0.16, 0.00 mmol/L), respectively; significant reductions were observed with whole flaxseed (-0.21 and -0.16 mmol/L, respectively) and lignan (-0.28 and -0.16 mmol/L, respectively) supplements but not with flaxseed oil. The cholesterol-lowering effects were more apparent in females (particularly postmenopausal women), individuals with high initial cholesterol concentrations, and studies with higher Jadad scores. No significant changes were found in the concentrations of HDL cholesterol and triglycerides. CONCLUSIONS Flaxseed significantly reduced circulating total and LDL-cholesterol concentrations, but the changes were dependent on the type of intervention, sex, and initial lipid profiles of the subjects. Further studies are needed to determine the efficiency of flaxseed on lipid profiles in men and premenopausal women and to explore its potential benefits on other cardiometabolic risk factors and prevention of cardiovascular disease.

Dietary Carbohydrates, Refined Grains, Glycemic Load, and Risk of Coronary Heart Disease in Chinese Adults

The potential long-term association between carbohydrate intake and the risk of coronary heart disease (CHD) remains unclear, especially among populations who habitually have high-carbohydrate diets. We prospectively examined intakes of carbohydrates and staple grains as well as glycemic index and glycemic load in relation to CHD among 117,366 Chinese women and men (40-74 years of age) without history of diabetes, CHD, stroke, or cancer at baseline in Shanghai, China. Diet was assessed using validated food frequency questionnaires. Incident CHD cases were ascertained during follow-ups (in women, the mean was 9.8 years and in men, the mean was 5.4 years) and confirmed by medical records. Carbohydrate intake accounted for 67.5% of the total energy intake in women and 68.5% in men. Seventy percent of total carbohydrates came from white rice and 17% were from refined wheat products. Positive associations between carbohydrate intakess and CHD were found in both sexes (all P for heterogeneity > 0.35). The combined multivariate-adjusted hazard ratios for the lowest to highest quartiles of carbohydrate intake, respectively, were 1.00, 1.38, 2.03, and 2.88 (95% confidence interval: 1.44, 5.78; P for trend = 0.001). The combined hazard ratios comparing the highest quartile with the lowest were 1.80 (95% confidence interval: 1.01, 3.17) for refined grains and 1.87 (95% confidence interval: 1.00, 3.53) for glycemic load (both P for trend = 0.03). High carbohydrate intake, mainly from refined grains, is associated with increased CHD risk in Chinese adults.

Adherence to dietary guidelines and mortality: a report from prospective cohort studies of 134,000 Chinese adults in urban Shanghai

BACKGROUND A higher adherence to dietary recommendations, such as the Dietary Approaches to Stop Hypertension (DASH) and the Alternative Healthy Eating Index (AHEI), has been associated with lower morbidity and mortality from chronic diseases in Western populations. However, the health benefits of following the Dietary Guidelines for Chinese remain unknown. OBJECTIVE We examined adherence to the Chinese Food Pagoda (CHFP) in association with total and cause-specific mortality and compared associations with those of the DASH and AHEI. DESIGN Participants included 61,239 men and 73,216 women (aged 40-74 y) from 2 population-based prospective studies in Shanghai, China. Habitual dietary intakes were assessed at baseline in-person interviews by using validated food-frequency questionnaires. Deaths and underlying causes were identified through the Shanghai Vital Statistics Registry and follow-up home visits. RESULTS We documented 2954 deaths in men and 4348 deaths in women during mean follow-ups of 6.5 and 12.0 y, respectively. A higher CHFP score was associated with lower total mortality with multivariable-adjusted HRs of 0.67 (95% CI: 0.60, 0.75) in men and 0.87 (95% CI: 0.80, 0.95) in women when extreme quartiles were compared (both P-trend < 0.005). Decreased risks associated with a higher CHFP score were observed for cardiovascular disease, cancer, and diabetes mortality, particularly in men. A significantly lower total mortality was shown for adherence to specific recommendations on vegetables, fruit, legumes, fish, and eggs but not grains, dairy, meat, fat, and salt. A higher DASH score and AHEI also predicted lower mortality from all causes, cardiovascular disease, and diabetes but not cancer. CONCLUSIONS A greater compliance with Chinese or US dietary guidelines is associated with lower total mortality in Chinese adults. Favorable associations are more evident in men than women and more consistent for cardiometabolic mortality than cancer mortality.

Dairy Consumption, Type 2 Diabetes, and Changes in Cardiometabolic Traits: A Prospective Cohort Study of Middle-Aged and Older Chinese in Beijing and Shanghai

OBJECTIVE To prospectively investigate associations of dairy consumption with risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were recruited and followed for 6 years. Baseline dairy consumption was assessed by a 74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by gas chromatography coupled with flame ion detector. Cardiometabolic traits were measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%) participants reported any dairy consumption, with a median intake of 0.89 (interquartile range 0.19–1.03) serving/day. Compared with nonconsumers, the relative risks (RRs) of type 2 diabetes among those having 0.5–1 serving/day and >1 serving/day were 0.70 (95% CI 0.55–0.88) and 0.65 (0.49–0.85), respectively, after multivariate adjustment (Ptrend < 0.001), which were attenuated by further adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy consumption was associated with favorable changes in glucose, waist circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline values of dependent variables. Erythrocyte trans-18:1 isomers were significantly correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these dairy food biomarkers were associated with a lower risk of type 2 diabetes. The RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82 (0.65–1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a significantly lower risk of type 2 diabetes and favorable changes of cardiometabolic traits in Chinese.

Elevated Plasma Ferritin Is Associated with Increased Incidence of Type 2 Diabetes in Middle-Aged and Elderly Chinese Adults

Epidemiological studies suggest that elevated circulating ferritin is associated with heightened incident diabetes in mainly Western populations, although the results were not entirely consistent. We aimed to prospectively investigate the ferritin-diabetes association in an Asian population for the first time, to our knowledge, and also to examine this association with an updated meta-analysis. Our prospective study included 2198 community-living Chinese between 50 and 70 y of age in 2005. All individuals participated in a 6-y follow-up survey in 2011. Fasting plasma ferritin, high-sensitivity C-reactive protein (hsCRP), adiponectin, and γ-glutamyltransferase (GGT) were measured at baseline. A total of 538 incident diabetes cases were documented by self-reports and/or fasting glucose ≥7.0 mmol/L at the follow-up survey. After multiple adjustments, the RR of type 2 diabetes was 1.90 (95% CI: 1.37, 2.65) when comparing the highest with the lowest sex-specific ferritin quintile. The association remained significant after further controlling for BMI, hsCRP, adiponectin, and GGT. To update the evidence reported in previous meta-analyses, we searched all prospective studies evaluating the association between blood ferritin and incident diabetes on PubMed prior to October 24, 2012. Besides our prospective study, 9 additional studies were also included. The pooled RR was 1.60 (95% CI: 1.25, 2.04) when comparing the highest with the lowest category of ferritin with a moderate heterogeneity (I(2) = 49.0%; P = 0.03). A significant linear dose-response relationship was detected in this meta-analysis. Overall, our results indicate an independent and significant positive association between higher plasma ferritin, a marker of elevated body iron stores, and increased risk of developing type 2 diabetes in middle-aged and elderly Chinese adults, which is similar to Western populations.

Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men

Soy food intake has been associated with a reduced risk of coronary heart disease (CHD) in women, but its association with CHD in men is unclear [1–3]. Several studies have found sex differences in the associations of soy intake with metabolic syndrome, endothelial function, and other cardiovascular risk factors [4,5]. In the Shanghai Men’s Health Study [6], we investigated the association between soy food intake and incident CHD among 55,474 Chinese men (40–74 years) who were free of CHD, stroke, and cancer at baseline (2002–2006). We also examined the associations of soy intake with multiple CHD biomarkers in a subsample of 3,885 men who provided fasting blood samples and had no history of major chronic diseases at recruitment. Usual dietary intakes were assessed through in-person interviews using a validated food-frequency questionnaire [6]. Energy and nutrient intakes, including soy protein and isoflavones, were calculated based on 2002 Chinese Food Composition Table. Participants who reported extreme energy intake ( 4,200 kcal/day) were excluded from analysis. Dietary intakes were adjusted for total energy by using the residual method. Incident CHD cases (nonfatal myocardial infarction and fatal CHD) were ascertained via follow-up home visits (follow-up rate: 94%) and linkage to the Shanghai Vital Statistics Registry (>99% complete). The diagnosis of cases was further confirmed by reviewing medical records and/or death certificates. Hazard ratios of CHD and 95% confidence intervals were estimated using Cox regression with age as the timescale. Measurements of plasma biomarkers have been described previously and shown reasonable intra-assay and intra-person coefficients of variation [7]. Multivariable-adjusted geometric means of biomarkers by soy protein intake were calculated and compared using linear regression. Written informed consent was obtained from each participant. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institutional review boards of all participating institutes. The median soy protein intake was 9.5 g/day (interquartile range: 6.3–13.7 g/day). During a mean follow-up of 5.4 years, we identified and validated 217 incident CHD cases. Soy intake showed a positive, independent, and dose-response association with risk of CHD. After adjustment for several CHD risk factors and other dietary intakes (Table), the hazard ratios were 1 (referent), 1.23, 1.47, and 1.58 (95% confidence interval: 1.06–2.36) from the lowest to highest quartile of soy protein intake (P for trend =0.02). Restricted cubic spline analysis revealed that CHD risk increased gradually with increasing soy protein intake up to ~15 g/day (80th percentile); the increase in risk flattened off thereafter (Figure). Positive associations persisted in analyses confined to men without diabetes and family history of cardiovascular diseases and men had no or little change in soy intake in last 5 years. No effect modifications were found for obesity, physical activity, smoking, alcohol consumption, hypertension, soy intake during adolescence, and other dietary factors. Results did not change when the first year of follow-up was excluded. Similar positive associations were observed for soy isoflavones and total soy food consumption. Figure Risk of coronary heart disease by soy protein intake in the Shanghai Men’s Health Study (— hazard ratio, ---- 95% confidence interval)a Table Hazard ratio (95% confidence interval) of coronary heart disease by soy food intake in the Shanghai Men’s Health Study (n= 55,474) In cross-sectional analysis of biomarkers, soy intake was significantly associated with higher plasma concentrations of interleukin-8 (IL-8) and plasminogen activator inhibitor-1 (PAI-1). In the lowest and highest quartiles of soy protein intake, the multivariable-adjusted geometric means were 1.4 and 1.6 pg/ml for IL-8 and 17.6 and 18.9 ng/ml for PAI-1 (both P for trend <0.01). We did not find significant associations of soy intake with other biomarkers, including blood lipids, glucose, insulin, C-reactive protein, and adipokines. Few epidemiological studies, mainly from Asian populations, have investigated the relationship between soy food intake and incident CHD. A potential cardioprotective effect of soy foods has been reported in Chinese and Japanese women [1–3]. To our knowledge, our study is the first to focus on soy foods and risk of CHD in men and provide the evidence that habitual high soy intake may have adverse effects on the development of CHD in men. The mechanisms behind the possible adverse effects of high soy intake on cardiometabolic health in men are largely unknown. Elevated IL-8 and PAI-1 are markers of impaired vascular endothelium and hypercoagulable states. The positive associations of soy intake with these biomarkers observed in our study might provide some explanations. Previous studies have suggested sex-specific associations of soy foods with cardiometabolic health, with favorable associations observed in women and unfavorable associations in men [4,5]. Clinical trials to date overall found no influence of soy protein or isoflavones on endothelial function [8]. Some studies, nevertheless, did observe male-specific adverse effects of soy-supplemented diet on coagulation and fibrinolysis [5,9]. It is also possible that other mechanisms, e.g. sex hormonal pathways, or other components of soy products or metabolites, e.g. trimethylamine-N-oxide, a metabolite from soy lecithin by gut microbiota [10], may be responsible for the observed adverse associations in men. Major concerns of our study include potential dietary measurement errors and residual confounding. However, because of the prospective design, exposure misclassification is likely to be non-differential and result in an underestimation of the association. Although we cannot rule out the presence of residual confounding, we have adjusted for a range of potential confounders and found similar associations with and without multivariable adjustment. In conclusion, habitual high soy food intake may be associated with increased risk of incident CHD in middle-aged and older Chinese men; elevated plasma IL-8 and PAI-1 might be potential contributing factors.

Higher Dietary Choline Intake Is Associated with Lower Risk of Nonalcoholic Fatty Liver in Normal-Weight Chinese Women

BACKGROUND Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population. OBJECTIVE We examined the association between choline intake and nonalcoholic fatty liver. METHODS Participants included 56,195 Chinese women and men, 40-75 y of age, with no or negligible alcohol consumption and with no history of hepatitis, cardiovascular disease, or cancer. All participants reported undergoing liver ultrasonography. Fatty liver was defined by self-report of a physician diagnosis. Habitual dietary intakes were assessed via validated food-frequency questionnaires. RESULTS The average total choline intakes were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men. Major food sources were eggs, soy foods, red meat, fish, and vegetables. A higher choline intake was associated with lower risk of fatty liver; after adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01). The inverse association was attenuated after further adjustment for history of metabolic disease and, in particular, BMI. The corresponding ORs (95% CIs) were 0.88 (0.75, 1.03) in women (P-trend = 0.05) and 0.85 (0.68, 1.06) in men (P-trend = 0.09). Stratified analyses suggested a potential effect modification by obesity status in women; the OR (95% CI) across extreme quintiles was 0.72 (0.57, 0.91) in normal-weight women vs. 1.05 (0.84, 1.31) in overweight or obese women (P-trend = 0.007 vs. 0.99, P-interaction < 0.0001). CONCLUSION Higher dietary choline intake may be associated with lower risk of nonalcoholic fatty liver only in normal-weight Chinese women.

Dietary isoflavones, urinary isoflavonoids, and risk of ischemic stroke in women

BACKGROUND Hormone therapy has been shown to increase risk of ischemic stroke in women. Plant-derived estrogens, particularly soy isoflavones, are known to have some estrogenic effects and have been marketed as natural alternatives to hormone therapy. Concerns have been raised about whether high isoflavone exposure may be related to ischemic stroke risk as well. OBJECTIVE We examined the dietary intake of isoflavones and the urinary excretion of isoflavonoids in relation to risk of ischemic stroke in women. DESIGN A prospective cohort study was conducted in 66,832 Chinese women (aged 40-70 y) who had no cardiovascular disease or cancer at baseline. Usual dietary intakes were assessed via in-person interviews with the use of a validated food-frequency questionnaire. Incident strokes were ascertained during follow-up home visits and confirmed by medical records. We also conducted a nested case-control study in postmenopausal women who had never used hormone therapy, including 1422 incident ischemic stroke cases and 1422 controls individually matched by age, date and time of urine sample collection, time since last meal, and use of antibiotics. Urinary isoflavonoids were measured with the use of high-performance liquid chromatography coupled with mass spectrometry. RESULTS During a mean follow-up of 10 y, 3110 incident ischemic strokes were verified. Dietary isoflavone intake was associated with increased risk of ischemic stroke; multivariable-adjusted HRs from lowest to highest quintiles were 1.00, 1.05, 1.10, 1.11, and 1.24, respectively (95% CI: 1.08, 1.42; P-trend = 0.002). In the case-control study, a similar positive association was observed for dietary isoflavones, but no significant associations were shown for the urinary isoflavonoid concentration [OR: 1.01 (95% CI: 0.77, 1.32) for comparison of extreme quintiles]. CONCLUSIONS A habitually high intake of soy isoflavones may be associated with a modest but significant increase in risk of ischemic stroke in women. However, no association was shown for the urinary excretion of isoflavonoids.

Dietary Fat Intake and Lung Cancer Risk: A Pooled Analysis

Purpose Dietary fat may play a role in lung carcinogenesis. Findings from epidemiologic studies, however, remain inconsistent. In this pooled analysis of 10 prospective cohort studies from the United States, Europe, and Asia, we evaluated the associations of total and specific types of dietary fat with lung cancer risk. Methods Cox regression was used to estimate hazard ratios (HRs) and 95% CIs in each cohort. Study-specific risk estimates were pooled by random- or fixed-effects meta-analysis. The first 2 years of follow-up were excluded to address potential influence of preclinical dietary changes. Results Among 1,445,850 participants, 18,822 incident cases were identified (mean follow-up, 9.4 years). High intakes of total and saturated fat were associated with an increased risk of lung cancer (for highest v lowest quintile: HR, 1.07 and 1.14, respectively; 95% CI, 1.00 to 1.15 and 1.07 to 1.22, respectively; P for trend for both < .001). The positive association of saturated fat was more evident among current smokers (HR, 1.23; 95% CI, 1.13 to 1.35; P for trend < .001) than former/never smokers ( P for interaction = .004), and for squamous cell and small cell carcinoma (HR, 1.61 and 1.40, respectively; 95% CI, 1.38 to 1.88 and 1.17 to 1.67, respectively; P for trend for both < .001) than other histologic types ( P for heterogeneity < .001). In contrast, a high intake of polyunsaturated fat was associated with a decreased risk of lung cancer (HR, 0.92; 95% CI, 0.87 to 0.98 for highest v lowest quintile; P for trend = .02). A 5% energy substitution of saturated fat with polyunsaturated fat was associated with a 16% to 17% lower risk of small cell and squamous cell carcinoma. No associations were found for monounsaturated fat. Conclusion Findings from this large, international cohort consortium suggest that modifying dietary fat intake (ie, replacing saturated fat with polyunsaturated fat) may reduce lung cancer risk, particularly among smokers and for squamous cell and small cell carcinoma.