Portfolio Diet Score and Risk of Cardiovascular Disease: Findings From 3 Prospective Cohort Studies.

BACKGROUND: The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke. METHODS: We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol. RESULTS: During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; Ptrend<0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; Ptrend=0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; Ptrend=0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile. CONCLUSIONS: The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts.

Underweight in the first 2 years of life and nutrition risk in later childhood: a prospective cohort study.

BACKGROUND: Children with underweight in the first 2 years have lower body mass index z-score (zBMI) and height-for-age z-score (HAZ) in later childhood. It is not known if underweight in the first 2 years is associated with nutrition risk in later childhood. OBJECTIVE: (1) Determine the relationship between underweight (zBMI < -2) in the first 2 years and nutrition risk measured by the Nutrition Screening for Toddlers and Preschoolers (NutriSTEP) score from 18 months to 5 years. (2) Explore the relationship between underweight in the first 2 years and the NutriSTEP subscores for eating behaviours and dietary intake from 18 months to 5 years. METHODS: This was a prospective study, including healthy full-term children in Canada aged 0-5 years. zBMI was calculated using measured heights and weights and the WHO growth standards. NutriSTEP score was measured using a parent-completed survey and ranged from 0 to 68. Nutrition risk was defined as a score ≥21. Linear mixed effects models were used. RESULTS: Four thousand nine hundred twenty-nine children were included in this study. At enrolment, 51.9% of participants were male. The prevalence of underweight children was 8.8%. Underweight in the first 2 years was associated with higher NutriSTEP (0.79, 95% CI: 0.29,1.29), higher eating behaviour subscore (0.24, 95% CI: 0.03, 0.46) at 3 years and higher odds of nutrition risk (OR: 1.39, 95% CI: 1.07,1.82) at 5 years. CONCLUSIONS: Children with underweight in the first 2 years had higher nutrition risk in later childhood. Further research is needed to understand the factors which influence these relationships.

The Environmental Sustainability of Plant-Based Dietary Patterns: A Scoping Review.

BACKGROUND: A large part of the existential threat associated with climate change is the result of current human feeding patterns. Over the last decade, research evaluating the diet-related environmental impacts of plant-based diets has emerged, and a synthesis of the available data is now due. OBJECTIVES: The objectives of the study were as follows: 1) to compile and summarize the literature on diet-related environmental impacts of plant-based dietary patterns; 2) to assess the nature of the data on impacts of plant-based dietary patterns on both environmental parameters and health (e.g., if land use is reduced for a particular diet, is cancer risk also reduced?); and 3) to determine where sufficient data exist for meta-analyses, in addition to identifying gaps within the literature. METHODS: Global peer-reviewed studies on the environmental impacts of plant-based diets were searched in Ovid MEDLINE, EMBASE, and Web of Science. After removing duplicates, the screening identified 1553 records. After 2 stages of independent review by 2 reviewers, 65 records met the inclusion criteria and were eligible to be used in synthesis. RESULTS: Evidence suggests that plant-based diets may offer lower greenhouse gas emissions (GHGEs), land use, and biodiversity loss than offered by standard diets; however, the impact on water and energy use may depend on the types of plant-based foods consumed. Further, the studies were consistent in demonstrating that plant-based dietary patterns that reduce diet-related mortality also promote environmental sustainability. CONCLUSIONS: Overall, there was agreement across the studies regarding the impact of plant-based dietary patterns on GHGE, land used, and biodiversity loss despite varied plant-based diets assessed.

Metabolomic profile of combined healthy lifestyle behaviours in humans: A systematic review.

A combination of healthy lifestyle behaviours (i.e., regular physical activity, nutritious diet, no smoking, moderate alcohol, and healthy body mass) has been consistently associated with beneficial health outcomes including reduced risk of cardiometabolic diseases. Metabolomic profiles, characterized by distinct sets of biomarkers, have been described for healthy lifestyle behaviours individually and in combination. However, recent literature calls for systematic evaluation of these heterogenous data to identify potential clinical biomarkers relating to a combined healthy lifestyle. The objective was to systematically review existing literature on the metabolomic profile of combined healthy lifestyle behaviours. MEDLINE, EMBASE and Cochrane databases were searched through March 2022. Studies in humans outlining the metabolomic profile of a combination of two or more healthy lifestyle behaviours were included. Collectively, the metabolomic profile following regular adherence to combined healthy lifestyle behaviours points to a positive association with beneficial fatty acids and phosphocreatine, and inverse associations with triglycerides, trimethylamine N-oxide, and acylcarnitines. The findings suggest that a unique metabolomic profile is associated with combined healthy lifestyle behaviours. Additional research is warranted to further describe this metabolomic profile using targeted and untargeted metabolomic approaches along with uniform definitions of combined healthy lifestyle variables across populations.

Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults.

BACKGROUND: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest. METHODS: We examined associations between consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional's Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses' Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. RESULTS: We documented 36 436 deaths (7896 cardiovascular disease [CVD] and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (<1/mo, 1-4/mo, 2-6/week, 1-<2/d, and ≥2/d) were 1.00 (reference), 1.01 (0.98, 1.04), 1.06 (1.03, 1.09), 1.14 (1.09, 1.19), and 1.21 (1.13, 1.28; P trend <0.0001). The association was observed for CVD mortality (hazard ratio comparing extreme categories was 1.31 [95% confidence interval, 1.15, 1.50], P trend <0.0001) and cancer mortality (1.16 [1.04, 1.29], P trend =0.0004). ASBs were associated with total and CVD mortality in the highest intake category only; pooled hazard ratios (95% confidence interval) across categories were 1.00 (reference), 0.96 (0.93, 0.99), 0.97 (0.95, 1.00), 0.98 (0.94, 1.03), and 1.04 (1.02, 1.12; P trend = 0.01) for total mortality and 1.00 (reference), 0.93 (0.87, 1.00), 0.95 (0.89, 1.00), 1.02 (0.94, 1.12), and 1.13 (1.02, 1.25; P trend = 0.02) for CVD mortality. In cohort-specific analysis, ASBs were associated with mortality in NHS (Nurses' Health Study) but not in HPFS (Health Professionals Follow-up Study) ( P interaction, 0.01). ASBs were not associated with cancer mortality in either cohort. CONCLUSIONS: Consumption of SSBs was positively associated with mortality primarily through CVD mortality and showed a graded association with dose. The positive association between high intake levels of ASBs and total and CVD mortality observed among women requires further confirmation.

Circulating Very-Long-Chain SFA Concentrations Are Inversely Associated with Incident Type 2 Diabetes in US Men and Women.

BACKGROUND: Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors. OBJECTIVE: We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk. METHODS: We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables. RESULTS: During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0-18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| ≤ 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk. CONCLUSIONS: Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.

Substitution of sugar-sweetened beverages for other beverages and the risk of developing coronary heart disease: Results from the Harvard Pooling Project of Diet and Coronary Disease.

Sugar-sweetened beverage (SSB) intake is associated with metabolic disorders. The reduction of SSB intake has been promoted to prevent death and disability from chronic diseases. We investigated the association between SSB intake and the risk of coronary events and death, and assessed if substitution of coffee, tea, milk, fruit juice and artificially-sweetened beverages (ASB) for SSBs was associated with a reduced risk of coronary events and death. This was a follow-up study in which data from six studies were pooled and standard observational analyses were performed. Diet intake was assessed at baseline by food-frequency questionnaires. Hazard ratios (HRs) with 95% confidence intervals for the incidence of coronary events and deaths were calculated by Cox proportional hazards regression. The effect of substituting another beverage for SSBs was calculated by taking the difference in the individual effect estimates. During the median 8.2-year follow-up, 4248 coronary events and 1630 coronary deaths were documented among 284,345 individuals. 355 ml daily increase of SSB intake was associated with an increased risk of coronary events (HR: 1.08; 95%CI: 1.02, 1.14) and possibly coronary death (HR: 1.05; 95%CI: 0.96, 1.16). Substitution analyses suggested that replacing SSBs with coffee (HR: 0.93; 95%CI: 0.87, 1.00) or ASB (HR: 0.89; 95%CI: 0.83, 0.97), might be associated with a lower risk of developing coronary events. We found that SSB intake was associated with an increased risk of coronary events and possibly coronary death. Our findings also suggest that replacing SSB's with ASBs or coffee may lower the risk of developing CHD.

Sugar-Sweetened Soda Consumption Increases Diabetes Risk Among Mexican Women.

BACKGROUND: Epidemiological evidence supports an association between sugar-sweetened soda consumption and diabetes. However, evidence regarding this association is limited in countries that have recently undergone a nutritional transition. OBJECTIVE: We estimated the association between sugar-sweetened soda consumption and incident diabetes. We also determined if the association between sugar-sweetened soda and diabetes differs as a result of early life factors and potential genetic susceptibility. METHODS: We used data from the Mexican Teachers' Cohort including 72,667 women aged ≥25 y, free of diabetes, cardiovascular disease, and cancer at baseline. We assessed sugar-sweetened soda consumption using a validated food frequency questionnaire (FFQ) at baseline. Diabetes was self-reported. We used Cox proportional hazard regression models to estimate the association between quintiles of sugar-sweetend soda and diabetes. We also estimated the associaiton by increasing one serving per day (355 mL) of sugar-sweetened soda. We conducted prespecified subgroup analysis by potential effect modifiers, namely markers of energy balance of early life factors, family history of diabetes, and Amerindian admixture. RESULTS: During a median follow-up of 2.16 y (IQR 0.75-4.50) we identified 3,155 incident cases of diabetes. The median consumption of sugar-sweetened soda was 1.17 servings per day (IQR 0.47- 4.00). In multivariable analyses, comparing extreme quintiles showed that higher sugar-sweetened soda consumption was associated with diabetes incidence (HR = 1.32; 95% CI: 1.17, 1.49), and each additional serving per day of sugar-sweetened soda was associated with an increase of 27% in diabetes incidence (HR = 1.27; 95% CI: 1.16, 1.38). The soda-diabetes association was stronger among women who experienced intrauterine and childhood over-nutrition (high birth weight, no short stature, higher adiposity in premenarche, and higher adiposity at age 18-20 y old). CONCLUSION: Sugar-sweetened soda consumption is associated with an increased risk of diabetes among Mexican women in a magnitude similar to that reported in other populations. The stronger association among individuals with markers of early life over-nutrition reinforce the need for early life interventions.

Identification of Plasma Lipid Metabolites Associated with Nut Consumption in US Men and Women.

BACKGROUND: Intake of nuts has been inversely associated with risk of type 2 diabetes and cardiovascular disease, partly through inducing a healthy lipid profile. How nut intake may affect lipid metabolites remains unclear. OBJECTIVE: The aim of this study was to identify the plasma lipid metabolites associated with habitual nut consumption in US men and women. METHODS: We analyzed cross-sectional data from 1099 participants in the Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Metabolic profiling was conducted on plasma by LC-mass spectrometry. Nut intake was estimated from food-frequency questionnaires. We included 144 known lipid metabolites that had CVs ≤25%. Multivariate linear regression was used to assess the associations of nut consumption with individual plasma lipid metabolites. RESULTS: We identified 17 lipid metabolites that were significantly associated with nut intake, based on a 1 serving (28 g)/d increment in multivariate models [false discovery rate (FDR) P value <0.05]. Among these species, 8 were positively associated with nut intake [C24:0 sphingomyelin (SM), C36:3 phosphatidylcholine (PC) plasmalogen-A, C36:2 PC plasmalogen, C24:0 ceramide, C36:1 PC plasmalogen, C22:0 SM, C34:1 PC plasmalogen, and C36:2 phosphatidylethanolamine plasmalogen], with changes in relative metabolite level (expressed in number of SDs on the log scale) ranging from 0.36 to 0.46 for 1 serving/d of nuts. The other 9 metabolites were inversely associated with nut intake with changes in relative metabolite level ranging from -0.34 to -0.44. In stratified analysis, 3 metabolites were positively associated with both peanuts and peanut butter (C24:0 SM, C24:0 ceramide, and C22:0 SM), whereas 6 metabolites were inversely associated with other nuts (FDR P value <0.05). CONCLUSIONS: A panel of lipid metabolites was associated with intake of nuts, which may provide insight into biological mechanisms underlying associations between nuts and cardiometabolic health. Metabolites that were positively associated with intake of nuts may be helpful in identifying potential biomarkers of nut intake.

Nepal Pioneer Worksite Intervention Study to lower cardio-metabolic risk factors: design and protocol.

BACKGROUND: To increase cardiovascular disease prevention efforts, worksite interventions can promote healthy food choices, facilitate health education, increase physical activity and provide social support. This pioneer study will measure the effectiveness of a cafeteria and a behavioral intervention on cardio-metabolic risk in a worksite in Nepal. METHODS: The Nepal Pioneer Worksite Intervention Study is a two-step intervention study conducted in Dhulikhel Hospital in eastern Nepal. In the first step, we will assess the effectiveness of a 6-month cafeteria intervention on cardio-metabolic risk using a pre-post design. In the second step, we will conduct a 6-month, open-masked, two-arm randomized trial by allocating half of the participants to an individual behavioral intervention based on the 'diabetes prevention program' for the prevention of cardio-metabolic risk. We will recruit 366 full time employees with elevated blood pressure, fasting blood sugar, or glycosylated haemoglobin (HbA1c). At baseline, we will measure their demographic variables, lifestyle factors, anthropometry, fasting blood sugar, HbA1c,and lipid profiles. We will measure cardio-metabolic outcomes at 6 months, 12 months, and 18 months. At 12 months, we will compare the proportion of participants who have attained two or more cardio-metabolic risk factor reduction goals (HbA1c decrease ≥0.5%; systolic blood pressure decrease ≥5 mmHg; or triglycerides decrease ≥10 mg/dL) during the cafeteria intervention period and the control period using generalized estimating equations. At 18 months, we will compare the proportion from the 'cafeteria only arm' to the 'cafeteria and behavior arm' for the same outcome using a chi-square test. DISCUSSION: This pioneer study will estimate the effect of environmental-level changes on lowering cardio-metabolic risks; and added benefit of an individual-level dietary intervention. If the study demonstrates a significant effect, a scaled up approach could produce an important reduction in cardiovascular disease burden through environmental and individual level prevention programs in Nepal and similar worksites worldwide. TRIAL REGISTRATION: The trial was retrospectively registered on clincaltrials.gov (Identification Member: NCT03447340 ; Date of Registration: February 27, 2018).

Cross-sectional association between sugar-sweetened beverage intake and cardiometabolic biomarkers in US women.

Few studies have evaluated the relationships between intake of sugar-sweetened beverages (SSB) and intermediate biomarkers of cardiometabolic risk. Associations between artificially sweetened beverages (ASB) and fruit juice with cardiometabolic biomarkers are also unclear. We investigated habitual SSB, ASB and fruit juice intake in relation to biomarkers of hepatic function, lipid metabolism, inflammation and glucose metabolism. We analysed cross-sectional data from 8492 participants in the Nurses' Health Study who were free of diabetes and CVD. Multivariate linear regression was used to assess the associations of SSB, ASB and fruit juice intake with concentrations of fetuin-A, alanine transaminase, γ-glutamyl transferase, TAG, HDL-cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein (CRP), intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1, adiponectin, insulin and HbA1c as well as total cholesterol:HDL-cholesterol ratio. More frequent intake of SSB was significantly associated with higher concentrations of fetuin-A, TAG, CRP, ICAM-1, adiponectin and insulin, a higher total cholesterol:HDL-cholesterol ratio, and a lower concentration of HDL-cholesterol (P trend ranges from <0·0001 to 0·04) after adjusting for demographic, medical, dietary and lifestyle variables. ASB intake was marginally associated with increased concentrations of CRP (P trend=0·04) and adiponectin (P trend=0·01). Fruit juice intake was associated with increased concentrations of TAG and HbA1c and a lower concentration of adiponectin (P trend ranges from <0·0001 to 0·01). In conclusion, habitual intake of SSB was associated with adverse levels of multiple cardiometabolic biomarkers. Associations between ASB and fruit juice with cardiometabolic risk markers warrant further exploration.

Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies.

AIMS/HYPOTHESIS: Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes. METHODS: We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses' Health Study, 84,310 women from the Nurses' Health Study II and 35,743 men from the Health Professionals' Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis. RESULTS: We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], p trend <0.0001; 1.29 [1.22, 1.36], p trend <0.0001 and 1.32 [1.24, 1.40], p trend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], p trend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], p trend <0.0001 for NEAP, PRAL and A:P, respectively). CONCLUSIONS/INTERPRETATION: This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.

Sugar sweetened beverages and cardiometabolic health.

PURPOSE OF REVIEW: It is widely accepted that sugar sweetened beverages (SSB) are implicated in weight gain and adverse cardiometabolic heath. To make informed recommendations about SSB, new evidence needs to be considered against existing literature. The present review will provide an update on the epidemiological and trial evidence linking intake of SSB to cardiometabolic outcomes. RECENT FINDINGS: The weight of the evidence from prospective cohort studies supports a strong positive association between intake of SSB and weight gain and risk type 2 diabetes (T2D) and coronary heart disease (CHD) that is independent of adiposity. Associations with stroke are less clear and suggestive of greater risk in women than men. Findings from short-term trials of SSB and markers of cardiometabolic risk including lipids, glucose, blood pressure, and inflammatory cytokines provide mechanistic support for associations with T2D and CHD. Putative underlying mechanisms include adverse glycemic effects and increased hepatic metabolism of fructose. SUMMARY: Conclusive evidence from epidemiological studies and trials on markers of cardiometabolic risk support an etiologic role of SSB in relation to weight gain and risk of T2D and CHD that is independent of weight. Continued efforts to reduce intake of SSB should be encouraged to improve the cardiometabolic health of individuals and populations.

Circulating Very-Long-Chain Saturated Fatty Acids and Incident Coronary Heart Disease in US Men and Women.

BACKGROUND: Circulating very-long-chain saturated fatty acids (VLCSFAs) may play an active role in the origin of cardiometabolic diseases. METHODS AND RESULTS: We measured 3 VLCSFAs (C20:0, C22:0, and C24:0) in plasma and erythrocytes using gas-liquid chromatography among 794 incident coronary heart disease (CHD) cases who were prospectively identified and confirmed among women in the Nurses' Health Study (NHS; 1990-2006) and among men in the Health Professionals Follow-Up Study (HPFS; 1994-2008). A total of 1233 CHD-free controls were randomly selected and matched to cases in these 2 cohorts. Conditional logistic regression was used to estimate hazard ratios and 95% confidence intervals. Plasma VLCSFAs were correlated with favorable profiles of blood lipids, C-reactive protein, and adiponectin in the NHS and HPFS and with fasting insulin and C-peptide levels in a nationally representative US comparison population. After multivariate adjustment for lifestyle factors, body mass index, diet, and long-chain n-3 and trans fatty acids, total VLCSFAs in plasma were associated with a 52% decreased risk of CHD (pooled hazard ratio, 0.48; 95% confidence interval, 0.32-0.72, comparing extreme quintiles; Ptrend<0.0001). For VLCSFAs in erythrocytes, a nonsignificant inverse trend with CHD risk was observed (pooled hazard ratio, 0.66; 95% confidence interval, 0.41-1.06, comparing extreme quintiles; Ptrend=0.16). CONCLUSIONS: In US men and women, plasma VLCSFAs were independently associated with favorable profiles of blood lipids and other cardiovascular disease risk markers and a lower risk of CHD. Erythrocyte VLCSFAs were associated with nonsignificant trends of lower CHD risk. Future studies are warranted to elucidate the underlying biological mechanisms.

Physical activity from menarche to first pregnancy and risk of breast cancer.

Breast tissue is particularly susceptible to exposures between menarche and first pregnancy, and a longer interval between these reproductive events is associated with elevated breast cancer risk. Physical activity during this time period may offset breast cancer risk, particularly for those at highest risk with longer menarche-to-first-pregnancy intervals. We used data from 65,576 parous women in the Nurses' Health Study II free of cancer in 1989 (baseline) and recalled their leisure-time physical activity at ages 12-34 in 1997. Current activity was collected at baseline and over follow-up. Relative risks (RRs) were estimated using multivariable Cox proportional hazards regression models. Between 1989 and 2011, 2,069 invasive breast cancer cases were identified. Total recreational activity between menarche and first pregnancy was not significantly associated with the risk of breast cancer. However, physical activity between menarche and first pregnancy was associated with significantly lower breast cancer risk among women in the highest category of a menarche-to first-pregnancy interval (≥20 years; RR for the highest versus the lowest quartile = 0.73, 95% confidence interval = 0.55-0.97; Ptrend = 0.045; Pinteraction = 0.048). This was not observed in women with a shorter interval. Physical activity between menarche and first pregnancy was associated with a lower risk of breast cancer among women with at least 20 years between these reproductive events. This may provide a modifiable factor that women can intervene on to mitigate their breast cancer risk associated with a longer interval.

Dietary Protein Intake and Risk of Type 2 Diabetes in US Men and Women.

Dietary proteins are important modulators of glucose metabolism. However, few longitudinal studies have evaluated the associations between intake of protein and protein type and risk of type 2 diabetes (T2D). We investigated the associations between total, animal, and vegetable protein and incident T2D in 72,992 women from the Nurses' Health Study (1984-2008), 92,088 women from Nurses' Health Study II (1991-2009) and 40,722 men from the Health Professionals Follow-up Study (1986-2008). During 4,146,216 person-years of follow-up, we documented 15,580 cases of T2D. In pooled multivariate models including body mass index, participants in the highest quintiles of percentage of energy derived from total protein and animal protein had 7% (95% confidence interval (CI): 1, 17) and 13% (95% CI: 6, 21) increased risks of T2D compared with those in the lowest quintiles, respectively. Percentage of energy intake from vegetable protein was associated with a moderately decreased risk of T2D (comparing extreme quintiles, hazard ratio =0.91, 95% CI: 0.84, 0.98). Substituting 5% of energy intake from vegetable protein for animal protein was associated with a 23% (95% CI: 16, 30) reduced risk of T2D. In conclusion, higher intake of animal protein was associated with an increased risk of T2D, while higher intake of vegetable protein was associated with a modestly reduced risk.

High Fiber and Low Starch Intakes Are Associated with Circulating Intermediate Biomarkers of Type 2 Diabetes among Women.

BACKGROUND: Carbohydrate quality has been consistently related to the risk of type 2 diabetes (T2D). However, limited information is available about the effect of carbohydrate quality on biomarkers related to T2D. OBJECTIVE: We examined the associations of carbohydrate quality measures (CQMs) including carbohydrate intake; starch intake; glycemic index; glycemic load; total, cereal, fruit, and vegetable fiber intakes; and different combinations of these nutrients with plasma concentrations of adiponectin, C-reactive protein (CRP), and glycated hemoglobin (HbA1c). METHODS: This is a cross-sectional analysis of 2458 diabetes-free women, ages 43-70 y, in the Nurses Health Study. CQMs were estimated from food-frequency questionnaires, and averages from 1984, 1986, and 1990 were used. Plasma biomarkers were collected in 1990. Multiple linear regression models were used to assess the associations between CQMs and biomarkers. RESULTS: After age, body mass index, lifestyle, and dietary variables were adjusted, 1) total fiber intake was positively associated with adiponectin (P-trend = 0.004); 2) cereal fiber intake was positively associated with adiponectin and inversely associated with CRP, and fruit fiber intake was negatively associated with HbA1c concentrations (all P-trend < 0.03); 3) starch intake was inversely associated with adiponectin (P-trend = 0.02); 4) a higher glycemic index was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); 5) a higher carbohydrate-to-total fiber intake ratio was associated with lower adiponectin (P-trend = 0.005); 6) a higher starch-to-total fiber intake ratio was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); and 7) a higher starch-to-cereal fiber intake ratio was associated with lower adiponectin (P-trend = 0.002). CONCLUSIONS: A greater fiber intake and a lower starch-to-fiber intake ratio are favorably associated with adiponectin and HbA1c, but only cereal fiber intake was associated with CRP in women. Further research is warranted to understand the potential mechanism of these associations in early progression of T2D.

Determinants and Consequences of Obesity.

OBJECTIVES: To review the contribution of the Nurses' Health Studies (NHS and NHS II) in addressing hypotheses regarding risk factors for and consequences of obesity. METHODS: Narrative review of the publications of the NHS and NHS II between 1976 and 2016. RESULTS: Long-term NHS research has shown that weight gain and being overweight or obese are important risk factors for type 2 diabetes, cardiovascular diseases, certain types of cancers, and premature death. The cohorts have elucidated the role of dietary and lifestyle factors in obesity, especially sugar-sweetened beverages, poor diet quality, physical inactivity, prolonged screen time, short sleep duration or shift work, and built environment characteristics. Genome-wide association and gene-lifestyle interaction studies have shown that genetic factors predispose individuals to obesity but that such susceptibility can be attenuated by healthy lifestyle choices. This research has contributed to evolving clinical and public health guidelines on the importance of limiting weight gain through healthy dietary and lifestyle behaviors. CONCLUSIONS: The NHS cohorts have contributed to our understanding of the risk factors for and consequences of obesity and made a lasting impact on clinical and public health guidelines on obesity prevention.

Reducing the global burden of type 2 diabetes by improving the quality of staple foods: The Global Nutrition and Epidemiologic Transition Initiative.

BACKGROUND: The prevalence of type 2 diabetes has been reaching epidemic proportions across the globe, affecting low/middle-income and developed countries. Two main contributors to this burden are the reduction in mortality from infectious conditions and concomitant negative changes in lifestyles, including diet. We aimed to depict the current state of type 2 diabetes worldwide in light of the undergoing epidemiologic and nutrition transition, and to posit that a key factor in the nutrition transition has been the shift in the type and processing of staple foods, from less processed traditional foods to highly refined and processed carbohydrate sources. DISCUSSION: We showed data from 11 countries participating in the Global Nutrition and Epidemiologic Transition Initiative, a collaborative effort across countries at various stages of the nutrition-epidemiologic transition whose mission is to reduce diabetes by improving the quality of staple foods through culturally-appropriate interventions. We depicted the epidemiologic transition using demographic and mortality data from the World Health Organization, and the nutrition transition using data from the Food and Agriculture Organization food balance sheets. Main staple foods (maize, rice, wheat, pulses, and roots) differed by country, with most countries undergoing a shift in principal contributors to energy consumption from grains in the past 50 years. Notably, rice and wheat products accounted for over half of the contribution to energy consumption from staple grains, while the trends for contribution from roots and pulses generally decreased in most countries. Global Nutrition and Epidemiologic Transition Initiative countries with pilot data have documented key barriers and motivators to increase intake of high-quality staple foods. Global research efforts to identify and promote intake of culturally-acceptable high-quality staple foods could be crucial in preventing diabetes. These efforts may be valuable in shaping future research, community interventions, and public health and nutritional policies.

Study design and methods for a randomized crossover trial substituting brown rice for white rice on diabetes risk factors in India.

India has the second largest number of people with diabetes in the world following China. Evidence indicates that consumption of whole grains can reduce the risk of type 2 diabetes. This article describes the study design and methods of a trial in progress evaluating the effects of substituting whole grain brown rice for polished (refined) white rice on biomarkers of diabetes risk (glucose metabolism, dyslipidemia, inflammation). This is a randomized controlled clinical trial with a crossover design conducted in Chennai, India among overweight but otherwise healthy volunteers aged 25-65 y with a body mass index ≥23 kg/m(2) and habitual rice consumption ≥200 g/day. The feasibility and cultural appropriateness of this type of intervention in the local environment will also be examined. If the intervention is efficacious, the findings can be incorporated into national-level policies which could include the provision of brown rice as an option or replacement for white rice in government institutions and food programs. This relatively simple dietary intervention has the potential to substantially diminish the burden of diabetes in Asia and elsewhere.