Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.

Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

[Analysis of the safety and efficacy of bronchial thermoplasty for severe asthma with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred)<60].

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in severe asthma patients with the first second forced expiratory volume (FEV(1)) as a percentage of the predicted value (FEV(1)%pred) <60%. Methods: A retrospective analysis was performed on 75 patients with asthma who were treated with BT at Shenzhen University Hospital of the Chinese Academy of Sciences from January 2016 to January 2018. The patients were divided into two groups based on the FEV(1)%pred before treatment: FEV(1)%pred <60% group (39 cases) and FEV(1)%pred ≥60% group (36 cases). Comparative analysis of glucocorticoid consumption, times of acute attack, asthma control test (ACT) score, changes in lung function, and adverse reactions at 3 weeks after treatment were performed between the two groups of patients. Results: Before BT treatment, the consumption of oral prednisone, the amount of budesonide inhaled, and the times of acute attack [M (Q(1), Q(3))] in the FEV(1)%pred <60% group were significantly greater than those in the FEV(1)%pred ≥60% group, and the ACT score was significantly lower than the FEV(1)%pred ≥60% group [10.00 (0, 20.00) vs 0(0, 3.75) mg/d, 960 (320, 960) vs 320 (320, 640) µg/d, 5(4, 8) vs 4 (4, 5) times/year, 13 (9, 15) vs 17 (13, 19) scores] (all P<0.05). Except that the oral prednisone dosage in the FEV(1)%pred<60% group was still higher 1 year after treatment [0 (0, 5.00) vs 0 (0, 0) mg/d] (P=0.009), there was no significant difference in the remaining indicators between the two groups 1 year after treatment and 2 years after treatment (all P>0.05). After 1 year and 2 years of treatment, all indicators in the two groups were better than before treatment (all P<0.05). The inhaled budesonide amount and the times of acute exacerbation in the FEV(1)%pred <60% group 2 years after treatment were less than those 1 year after treatment [320 (320, 320) vs 320 (320, 640) µg/d, 0 (0, 0) vs 0(0, 1) times/year] (all P<0.05), and there was no significant difference in the remaining indicators. In the FEV(1)%pred ≥60% group, there was no significant difference between 2 years after treatment and 1 year after treatment in the above indicators except the amount of inhaled budesonide (all P>0.05). In the FEV(1)%pred <60% group, FEV(1) and the FEV(1)%pred were significantly lower than the FEV(1)%pred ≥60% group before treatment, 1 year after treatment and 2 years after treatment [FEV(1):(1.21±0.41) vs (2.26±0.80)L, (1.84±0.73) vs (2.30±0.78)L, (1.70±0.66) vs (2.38±0.76)L; FEV(1)%pred:46.2 (38.5, 53.7)% vs 80.8(66.5, 93.6)%, 60.1 (48.2, 71.6)% vs 87.4 (68.5, 96.5)%, 58.5 (48.6, 74.8)% vs 86.6 (73.0, 97.3)%] (all P<0.05). In the FEV(1)%pred <60% group, FEV(1) and FEV(1)%pred 1 year after treatment and 2 years after treatment were all increased compared with before treatment (all P<0.05). In the FEV(1)%pred ≥60% group, there was no statistical difference in FEV(1) at each time point before and after treatment (all P>0.05), but the FEV(1)%pred at 2 years after treatment was higher than before treatment (P<0.05). There were no significant differences in adverse events between the two groups (all P>0.05). Conclusion: BT can significantly improve the lung function, reduce the times of acute attack and the dosage of glucocorticoids in severe asthma patients with FEV(1)% pred<60%, which is safe and effective.

Substituting brown rice for white rice on diabetes risk factors in India: a randomised controlled trial.

India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25-65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (-0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.

Body shape trajectories and incidence of depression in the "Seguimiento Universidad de Navarra" (SUN) prospective cohort.

BACKGROUNDS AND AIM: The association between trajectories of body-shape from early childhood to early adulthood (first 40 years of life) and subsequent depression risk has not been explored before. We assessed this association in a prospective cohort of university graduates. METHODS: We used a group-based modeling approach to assess the body shape trajectories from age 5 to 40 years, among 3888 women and 4124 men of the "Seguimiento Universidad de Navarra" (SUN) cohort study. All participants were free of depression at the beginning of the follow-up, and the occurrence of a new medical diagnosis of depression was evaluated every two years. RESULTS: Four distinct trajectories for women and men were found ("lean-moderate increase", "medium-stable", "heavy-medium" and "heavy-marked increase" for women and "lean-marked increase", "medium-marked increase", "medium-stable" and "heavy-stable" for men). Among 78,475 person-years of follow-up a total of 351 incident cases of depression were identified. Among women, compared to those who maintained a medium body shape during life span ("medium-stable" trajectory), women who were heavy at childhood and had a marked increase in their body shape during early adult life ("heavy-marked increase" trajectory) showed significantly higher risk of a new-onset depression [HR = 1.92 (1.18-3.13)]. No association was observed in men between body-shape trajectories and subsequent risk of depression. CONCLUSIONS: Our results suggest that in a Mediterranean cohort, women who were heavy at early childhood and showed marked increases in body shape during early adulthood were at higher risk of developing depression later in life.

Body shape trajectories and the incidence of hypertension in a Mediterranean cohort: The sun study.

AIMS: Our aim was to assess the association between trajectories of body-shape across the first 40 years of life and subsequent development of hypertension in a Mediterranean cohort. METHODS AND RESULTS: We used a group-based modeling approach to assess body shape trajectories from age 5 to 40 years, among 7514 participants included in the SUN study (1999-2016), and assessed the subsequent incidence of hypertension. To create the trajectories, we used a censored normal model as a polynomial function of age. Cox models were used to estimates hazard ratios (HR) for hypertension according to body shape trajectories. Identified trajectories were "childhood lean -mid-life increase", "childhood medium-mid-life stable", " childhood heavy -mid-life decrease", and "childhood heavy -mid-life increase" for women; and "childhood lean-mid-life increase", "childhood medium-mid-life stable", "childhood medium -mid-life increase" and "childhood heavy-mid-life stable" for men. After a follow-up of 63,068 person-years, 865 incident cases of hypertension were found. Among women, compared to those in the "childhood medium-mid-life stable" trajectory, those, in the "childhood heavy -mid-life increase" trajectory showed higher risk to develop hypertension [HR = 1.72 (1.17-2.53)]. In men, compared with those in the "childhood medium-mid-life stable" trajectory, those in the "childhood lean and childhood medium -mid-life increase" and the "childhood heavy- mid-life stable" trajectories showed higher subsequent incidence of hypertension [HR = 1.43 (1.11-1.85), HR = 1.52 (1.17-1.97) and HR = 1.56 (1.14-2.14), respectively] after adjusting for potential confounders (including age, lifestyles, dietary intake, personality traits, physical activity and sedentary behaviors). CONCLUSIONS: Our results suggest that mid-life increases in body shape or maintaining a heavy body shape during early and middle life in men and childhood heavy-mid-life increase in women is associated with a higher subsequent risk of developing hypertension in this Mediterranean population.

Olive oil and prevention of chronic diseases: Summary of an International conference.

Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

BACKGROUND: The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. OBJECTIVES: To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. SUBJECTS/METHODS: Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. RESULTS: Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (Ptrend=0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (Ptrend=0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05). CONCLUSIONS: In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Associations between benign cutaneous nevi and risk of Type 2 diabetes mellitus in men and women: results from two prospective cohort studies.

AIM: To examine the association of cutaneous nevi with Type 2 diabetes risk. METHODS: We prospectivly examined the associations between nevus count and risk of Type 2 diabetes among 26 240 men (1988-2010) from the Health Professionals Follow-up Study and 67 050 women (1986-2010) from the Nurses' Health Study. Information on the numbers of cutaneous nevi on arms at baseline and incident cases of Type 2 diabetes was collected using validated questionnaires. RESULTS: During 1 879 287 person-years of follow-up, we documented 9040 incident cases of Type 2 diabetes. After adjustment for age, BMI and other diabetes risk factors, greater number of nevi was associated with higher risk of Type 2 diabetes. Multivariable-adjusted hazard ratios for <1, 1-5, 6-14 and ≥15 nevi were 1.00 (reference), 1.02 (95% CI 0.93, 1.13), 1.08 (95% CI 0.88, 1.34) and 1.57 (95% CI 1.15, 2.15), respectively, for men (P for linear trend = 0.01), and 1.00 (reference), 1.07 (95% CI 1.02, 1.13), 0.98 (95% CI 0.87, 1.10), and 1.25 (1.01, 1.54), respectively, for women (P for linear trend = 0.05). This positive association remained consistent across subgroups stratified by age, BMI, multivitamin use, smoking status, alcohol, physical activity, history of hypercholesterolaemia, family history of diabetes, history of hypertension and menopausal status (in women). CONCLUSIONS: Cutaneous nevus count may represent a novel marker for development of Type 2 diabetes, suggesting a possible unique melanocytic nevus-related mechanism in the pathogenesis of Type 2 diabetes. Further studies are warranted to confirm the findings and to investigate the underlying mechanisms.

Healthful dietary patterns and long-term weight change among women with a history of gestational diabetes mellitus.

BACKGROUND/OBJECTIVE: Diet represents a key strategy for the prevention of obesity and type 2 diabetes among women with a history of gestational diabetes mellitus (GDM), although effective dietary patterns to prevent weight gain in the long term are largely unknown. We sought to evaluate whether improvement in overall diet quality is associated with less long-term weight gain among high-risk women with prior GDM. SUBJECTS/METHODS: Women with a history of GDM (N=3397) were followed from 1991 to 2011, or until diagnosis of type 2 diabetes or other chronic disease. Usual diet was assessed via food frequency questionnaire every 4 years from which we calculated the Alternative Healthy Eating Index (aHEI-2010), Alternate Mediterranean Diet (AMED) and Dietary Approaches to Stop Hypertension (DASH) dietary pattern scores. Weight, lifestyle and health-related outcomes were self-reported every 2 years. We estimated the change in dietary score with change in body weight using linear regression models adjusting for age, baseline body mass index (BMI), baseline and simultaneous change in physical activity and smoking status and other risk factors. RESULTS: Women were followed up to 20 years, gaining an average 1.9 kg (s.d.=7.0) per 4-year period. Women in the highest quintile (Q5) of diet change (most improvement in quality) gained significantly less weight per 4-year period than the lowest quintile (Q1; decrease in quality), independent of other risk factors (4-year weight change, aHEI-2010: Q5=1.30 kg vs Q1=3.27 kg; AMED: Q5=0.94 kg vs Q1=2.56 kg, DASH: Q5=0.64 kg vs Q1=2.75 kg). Significant effect modification by BMI (p-interactions <0.001) indicated a greater magnitude of weight change among women with a higher baseline BMI for all three patterns. CONCLUSIONS: Increased diet quality was associated with less weight gain, independent of other lifestyle factors. Post-partum recommendations on diet quality may provide one strategy to prevent long-term weight gain in this high-risk group.

Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts.

BACKGROUND/OBJECTIVES: Evidence regarding the consumption of soy foods and isoflavones in relation to risk of type 2 diabetes (T2D) is scarce. Our study was to evaluate the association between soy food and isoflavone consumption and risk of T2D in US men and women. SUBJECTS/METHODS: We followed 63 115 women in the Nurses' Health Study (1998-2012), 79 061 women in the Nurses' Health Study II (1999-2013) and 21 281 men in the Health Professionals Follow-Up Study (2002-2010). Diet was assessed by a validated food-frequency questionnaire and was updated every 4 years. Self-reports of incident T2D were confirmed by a validated supplementary questionnaire. RESULTS: During 1 966 321 person-years of follow-up, 9185 incident T2D cases were documented. After multivariate adjustment for covariates, consumption of soy foods (tofu and soy milk) was not associated with a lower T2D risk. Compared with non-consumers of soy foods, the hazard ratio (HR) was 1.00 (95% confidence interval (CI): 0.93, 1.07) for <1 serving/week and 0.93 (95% CI: 0.83, 1.03) for ⩾1 serving/week of soy foods (P for trend=0.14). In contrast, intake of total isoflavones was inversely associated with T2D risk. Comparing extreme quintiles of isoflavones, the HR was 0.89 (95% CI: 0.83, 0.96; P for trend=0.009). Inverse associations were also found for consumption of major individual isoflavones, including daidzein and genistein, with risk of T2D. CONCLUSIONS: Intake of isoflavones was associated with a modestly lower T2D risk in US men and women who typically consumed low-to-moderate amounts of soy foods. These findings warrant replications in other populations with similar soy intake levels.

Adherence to the Mediterranean dietary pattern and BMI change among US adolescents.

BACKGROUND: Among adults, the Mediterranean dietary pattern (MDP) is inversely related to body mass index (BMI). Data are lacking on adherence to the MDP among youth in the United States and whether the MDP is related to weight change in that group. OBJECTIVE: To assess whether adherence to the MDP was associated with BMI change among adolescents. To examine temporality, we studied the association between baseline and 2-3-year changes in adherence to the MDP with concurrent changes in BMI, as well as subsequent changes in BMI over a 7-year period. METHODS: We prospectively followed 6002 females and 4916 males in the Growing Up Today Study II, aged 8-15 years in 2004, living across United States. Data were collected by questionnaire in 2004, 2006, 2008 and 2011. Dietary intake was assessed by the Youth/Adolescent Questionnaire. The KidMed Index was derived to measure the adherence to the MDP. We used generalized estimating equations with repeated measures within subjects to assess the association between MDP and BMI change. RESULTS: A two-point increment in the KidMed Index was independently associated with a lower gain in BMI (-0.04 kg m(-2); P=0.001). A greater increase in adherence to the KidMed Index was independently related to a lower gain in BMI in both the concurrent (P-for-trend<0.001) and the subsequent period (P-for-trend=0.002). CONCLUSIONS: Adherence to MDP was inversely associated with change in BMI among adolescents. Two-year improvement in adherence to MDP was independently associated with less steep gain in the BMI in both the concurrent and the subsequent period.

Nut consumption and risk of colorectal cancer in women.

BACKGROUND/OBJECTIVES: Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer. SUBJECTS/METHODS: We prospectively followed 75,680 women who were free of cancer at baseline in the Nurses' Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2-4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: During 2,103,037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, ⩾ 56 g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72-1.05; P-trend: 0.06). No association was observed for peanut butter. CONCLUSIONS: In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors.

High levels of phosphatase and tensin homolog expression predict favorable prognosis in patients with non-small cell lung cancer.

OBJECTIVE: The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. PATIENTS AND METHODS: In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. RESULTS: NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 versus 12.9 months, log-rank p = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 versus 15.54 months, log-rank p = 0.043). High levels of PTEN expression resulted in 43% reduction in risk for all NSCLC patients (HR = 0.57, 95% CI: 0.33-0.98, p = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex and tumor type (HR = 0.56, 95% CI: 0.32-0.99; p = 0.048; HR = 0.54, 95% CI: 0.36-0.97; p = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (p > 0.17). When levels of PTEN expression were binarized using the optimal cutpoint, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80% and 58% respectively, p = 0.049) and in patients with AC than in those with squamous-cell carcinoma (SCC) (78% and 58% respectively, p = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (p > 0.28). CONCLUSIONS: Our results suggest that high levels of PTEN expression may be favorable prognostic marker in NSCLC patients.

Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women.

OBJECTIVE: Both bisphenol A (BPA) and phthalates are known endocrine-disrupting chemicals for which there is widespread general population exposure. Human exposure occurs through dietary and non-dietary routes. Although animal studies have suggested a potential role of these chemicals in obesity, evidence from human studies is sparse and inconsistent, and prospective evidence is lacking. This study evaluated urinary concentrations of BPA and major phthalate metabolites in relation to prospective weight change. METHODS: The study population was from the controls in a prospective case-control study of type 2 diabetes in the Nurses' Health Study (NHS) and NHSII. A total of 977 participants provided first-morning-void urine samples in 1996-2002. Urinary concentrations of BPA and nine phthalate metabolites were measured using liquid chromatography-mass spectrometry. Body weights were self-reported at baseline and updated biennially thereafter for 10 years. RESULTS: On average, the women gained 2.09 kg (95% confidence interval (CI), -2.27 to 6.80 kg) during the 10-year follow-up. In multivariate analysis with adjustment of lifestyle and dietary factors, in comparison with women in the lowest quartile of BPA concentration, those in the highest quartile had 0.23 kg per year (95% CI, 0.07-0.38 kg per year) greater weight gain during the 10-year follow-up (P-trend=0.02). Several phthalate metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also associated with faster prospective weight gain in a dose-response fashion (P-trend<0.01), whereas other phthalates metabolites, including MEP and monoethylhexyl phthalate, were not monotonically associated with body weight change. CONCLUSIONS: These data suggest urinary concentrations of BPA and certain individual phthalate metabolites that were associated with modestly greater weight gain in a dose-response fashion. These data are consistent with a potential role of BPA and phthalates in obesity, although more prospective data are needed to corroborate these observations.

Plasma 25-hydroxyvitamin D and risk of metabolic syndrome: an ancillary analysis in the Diabetes Prevention Program.

BACKGROUND/OBJECTIVES: Low blood levels of 25-hydroxyvitamin D (25OHD) have been associated with cardiometabolic disease but results are inconsistent. The objective of the study was to investigate the association of 25OHD with metabolic syndrome in a population at increased risk for diabetes. SUBJECTS/METHODS: Using baseline data from the placebo and lifestyle intervention arms of the Diabetes Prevention Program (N=2000), multivariable logistic regression models were used to estimate the odds of prevalent metabolic syndrome and each of its individual components across 25OHD tertiles. Multivariable linear regression was used to estimate the adjusted mean difference of insulin secretion and sensitivity across the same 25OHD tertiles. In participants free of metabolic syndrome at baseline (N=546), incident metabolic syndrome in the first 2 years of follow-up was assessed using discrete-time proportional hazards regression to test its association with 25OHD concentration. RESULTS: After multivariate adjustment, participants in the highest tertile of 25OHD had lower odds of prevalent metabolic syndrome (odds ratio=0.62; 95% confidence interval (CI)=0.45-0.84), smaller waist circumference, higher high-density lipoprotein and lower fasting plasma glucose compared with participants in the lowest tertile of 25OHD. Higher plasma 25OHD concentration was associated with greater insulin sensitivity and lower insulin secretion. After multivariate adjustment, there was a nonsignificant lower risk of metabolic syndrome in the highest tertile of 25OHD (hazard ratio=0.79; 95% CI=0.48-1.32) compared with the lowest tertile. CONCLUSIONS: In a population at increased risk for diabetes, higher plasma 25OHD concentration was inversely associated with prevalent metabolic syndrome and nonsignificantly with incident metabolic syndrome.

Nut consumption and risk of pancreatic cancer in women.

BACKGROUND: Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer. METHODS: We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. RESULTS: We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts ≥2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47-0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48-0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables. CONCLUSION: Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer.

Resolved: there is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases.

Sugar-sweetened beverages (SSBs) are the single largest source of added sugar and the top source of energy intake in the U.S. diet. In this review, we evaluate whether there is sufficient scientific evidence that decreasing SSB consumption will reduce the prevalence of obesity and its related diseases. Because prospective cohort studies address dietary determinants of long-term weight gain and chronic diseases, whereas randomized clinical trials (RCTs) typically evaluate short-term effects of specific interventions on weight change, both types of evidence are critical in evaluating causality. Findings from well-powered prospective cohorts have consistently shown a significant association, established temporality and demonstrated a direct dose-response relationship between SSB consumption and long-term weight gain and risk of type 2 diabetes (T2D). A recently published meta-analysis of RCTs commissioned by the World Health Organization found that decreased intake of added sugars significantly reduced body weight (0.80 kg, 95% confidence interval [CI] 0.39-1.21; P < 0.001), whereas increased sugar intake led to a comparable weight increase (0.75 kg, 0.30-1.19; P = 0.001). A parallel meta-analysis of cohort studies also found that higher intake of SSBs among children was associated with 55% (95% CI 32-82%) higher risk of being overweight or obese compared with those with lower intake. Another meta-analysis of eight prospective cohort studies found that one to two servings per day of SSB intake was associated with a 26% (95% CI 12-41%) greater risk of developing T2D compared with occasional intake (less than one serving per month). Recently, two large RCTs with a high degree of compliance provided convincing data that reducing consumption of SSBs significantly decreases weight gain and adiposity in children and adolescents. Taken together, the evidence that decreasing SSBs will decrease the risk of obesity and related diseases such as T2D is compelling. Several additional issues warrant further discussion. First, prevention of long-term weight gain through dietary changes such as limiting consumption of SSBs is more important than short-term weight loss in reducing the prevalence of obesity in the population. This is due to the fact that once an individual becomes obese, it is difficult to lose weight and keep it off. Second, we should consider the totality of evidence rather than selective pieces of evidence (e.g. from short-term RCTs only). Finally, while recognizing that the evidence of harm on health against SSBs is strong, we should avoid the trap of waiting for absolute proof before allowing public health action to be taken.

Changes in water and beverage intake and long-term weight changes: results from three prospective cohort studies.

OBJECTIVE: To examine the long-term relationship between changes in water and beverage intake and weight change. SUBJECTS: Prospective cohort studies of 50013 women aged 40-64 years in the Nurses' Health Study (NHS, 1986-2006), 52987 women aged 27-44 years in the NHS II (1991-2007) and 21988 men aged 40-64 years in the Health Professionals Follow-up Study (1986-2006) without obesity and chronic diseases at baseline. MEASURES: We assessed the association of weight change within each 4-year interval, with changes in beverage intakes and other lifestyle behaviors during the same period. Multivariate linear regression with robust variance and accounting for within-person repeated measures were used to evaluate the association. Results across the three cohorts were pooled by an inverse-variance-weighted meta-analysis. RESULTS: Participants gained an average of 1.45 kg (5th to 95th percentile: -1.87 to 5.46) within each 4-year period. After controlling for age, baseline body mass index and changes in other lifestyle behaviors (diet, smoking habits, exercise, alcohol, sleep duration, TV watching), each 1 cup per day increment of water intake was inversely associated with weight gain within each 4-year period (-0.13 kg; 95% confidence interval (CI): -0.17 to -0.08). The associations for other beverages were: sugar-sweetened beverages (SSBs) (0.36 kg; 95% CI: 0.24-0.48), fruit juice (0.22 kg; 95% CI: 0.15-0.28), coffee (-0.14 kg; 95% CI: -0.19 to -0.09), tea (-0.03 kg; 95% CI: -0.05 to -0.01), diet beverages (-0.10 kg; 95% CI: -0.14 to -0.06), low-fat milk (0.02 kg; 95% CI: -0.04 to 0.09) and whole milk (0.02 kg; 95% CI: -0.06 to 0.10). We estimated that replacement of 1 serving per day of SSBs by 1 cup per day of water was associated with 0.49 kg (95% CI: 0.32-0.65) less weight gain over each 4-year period, and the replacement estimate of fruit juices by water was 0.35 kg (95% CI: 0.23-0.46). Substitution of SSBs or fruit juices by other beverages (coffee, tea, diet beverages, low-fat and whole milk) were all significantly and inversely associated with weight gain. CONCLUSION: Our results suggest that increasing water intake in place of SSBs or fruit juices is associated with lower long-term weight gain.

Erythrocyte trans-fatty acids, type 2 diabetes and cardiovascular risk factors in middle-aged and older Chinese individuals.

AIMS/HYPOTHESIS: Few data are available about intakes and food sources of trans-fatty acids (TFAs) or their associations with cardiometabolic outcomes in Asian people who consume a prudent diet but are experiencing rapid nutritional transitions. We aimed to investigate the relationships between TFA biomarkers and type 2 diabetes and cardiovascular risk factors in Chinese individuals. METHODS: Erythrocyte fatty acids were measured by gas chromatography among 3,107 men and women (50-70 years) recruited from urban and rural areas in Beijing and Shanghai, China. RESULTS: Total trans-18:1 and two trans-18:2 isomers were detected and accounted for 0.37% of the total fatty acids in the erythrocytes. Concentrations of TFAs were higher in women than men, and in urban than rural residents. Of the TFAs, trans-18:1, but not trans-18:2, showed a modest association with dairy consumption (ß = 0.27), but not with other foods. After adjustment for BMI, social-demographic, lifestyle and dietary factors and other TFAs, erythrocyte trans-18:1 was shown to be associated with a lower risk of type 2 diabetes (OR comparing extreme [first and fourth] quartiles 0.68, 95% CI 0.48, 0.97, p(trend) = 0.02), as well as 20-50% lower odds of central obesity, dyslipidaemia, hyperglycaemia, insulin resistance and chronic inflammation. In contrast, trans-18:2 fatty acids were positively associated with high triacylglycerol (p(trend) < 0.001) and LDL-cholesterol (p(trend) = 0.03) levels, but not with diabetes and other cardiometabolic risk factors. CONCLUSIONS/INTERPRETATION: Among middle-aged and older Chinese individuals with overall low erythrocyte TFAs levels, trans-18:1 might serve as a marker of dairy intake. Higher trans-18:1 levels were associated with a lower risk of type 2 diabetes, whereas higher trans-18:2 levels were associated with dyslipidaemia.