Importance:Weight gain is common during menopause, and healthy dietary patterns are key to its management. However, effectiveness of different diets for weight management during this period remains unclear. Objective:To examine and compare associations of multiple dietary patterns with weight gain and obesity risk in the years surrounding menopause. Design, Setting, and Participants:This prospective, population-based cohort study included women observed over a 12-year period surrounding menopause in the Nurses' Health Study II (1989-2019). Data analysis was performed between November 2024 and May 2025. Exposures:Diet was assessed every 4 years using validated food frequency questionnaires. Dietary scores included the plant-based diet index (PDI), healthy PDI, unhealthy PDI, Mediterranean diet, Dietary Approaches to Stop Hypertension, Planetary Health Diet Index (PHDI), low-carbohydrate diet (LCD), healthy LCD, unhealthy LCD, empirical dietary inflammatory pattern, empirical dietary index for hyperinsulinemia (EDIH), and ultraprocessed food intake. Main Outcomes and Measures:The outcomes were annual changes in self-reported body weight (kilograms per year) and incident obesity. Generalized estimating equations were used to estimate annual weight change across dietary patterns. Cox proportional hazards models were used to estimate risk of obesity across dietary patterns. Results:Among 38 283 women (mean [SD] age, 45.6 [3.0] years), the mean (SD) weight gain was 0.80 (1.00) kg per year. During 340 122 person-years of follow-up, 5214 women developed obesity. After adjusting for age, race and ethnicity, marital status, income, postmenopausal hormone therapy use, parity, smoking, alcohol, energy intake, physical activity, and baseline body mass index, the reverse EDIH (quintile 5 vs 1) was associated with the largest reduction in weight gain (mean, -0.28 kg/y; 95% CI, -0.30 to -0.26 kg/y). For incident obesity, the lowest risk was observed for the PHDI (hazard ratio, 0.46; 95% CI, 0.42 to 0.51) and reverse EDIH (hazard ratio, 0.51; 95% CI, 0.46 to 0.56). EDIH showed the largest positive correlations with red or processed meats, sodium, and French fries. PHDI showed the largest positive correlations with nuts, unsaturated fats, whole grain carbohydrates, and vegetable protein. Conclusions and Relevance:In this prospective cohort study of women during menopause, adopting low-insulinemic and planetary health diets, low in red and processed meats, sodium, potatoes, and French fries and rich in nuts, legumes, fruits, vegetables, and whole grains, was associated with optimized weight management.

BACKGROUND:Previous cohort studies of physical activity and cognitive health have often been limited by small sample sizes, short follow-up durations, absence of long-term assessments of physical activity, and potential reverse causation. We aimed to prospectively examine the associations between long-term physical activity and multiple cognitive outcomes. METHODS:In this study, we used data from two ongoing US prospective cohorts: the Nurses' Health Study (established in 1976, comprising 121 700 female registered nurses aged 30-55 years at enrolment) and the Health Professionals Follow-Up Study (HPFS; established in 1986, comprising 51 492 male health professionals aged 40-75 years at enrolment). Discretionary physical activity was assessed approximately every 2-4 years using self-report questionnaires, beginning in 1986 for both cohorts. Total physical activity, walking, and vigorous aerobic exercise were each expressed as the summed metabolic equivalent of task hours per week. We ascertained incident dementia cases (a composite endpoint of self-reported physician-diagnosed dementia and deaths due to dementia) in eligible Nurses' Health Study participants (1990-2023) and HPFS participants (1990-2023); deaths due to dementia were confirmed using medical records, death certificates, and autopsy reports. Objective cognitive function was assessed in Nurses' Health Study participants only (1995-2008) using the Telephone Interview for Cognitive Status (TICS). Subjective cognitive decline was self-reported by Nurses' Health Study participants (followed up in 2012 and 2014) and HPFS participants (followed up in 2008, 2012, 2016, 2018, and 2020) via questionnaires with binary questions that assessed subjective cognitive concerns across multiple domains. Participants were excluded from the analysis if they had dementia, stroke, cancer, were missing total physical activity or walking data, or reported difficulties with walking at baseline. Outcomes were analysed using multivariable-adjusted regression models. We used a 4-year lag approach in our main analyses to minimise the potential for reverse causation. FINDINGS:Our final samples comprised 63 596 Nurses' Health Study participants and 43 440 HPFS participants for the dementia endpoints, 13 647 Nurses' Health Study participants for assessing objective cognitive function, and 29 801 Nurses' Health Study participants and 17 162 HPFS participants for assessing subjective cognitive decline. Compared with participants in the lowest quartile for total physical activity, those in the highest quartile had a lower risk of dementia (hazard ratio [HR] 0·72, 95% CI 0·68-0·76; p<0·0001 for trend) and subjective cognitive decline (relative risk [RR] 0·77, 95% CI 0·73-0·80; p<0·0001 for trend). Being in the highest versus the lowest tertile for walking or vigorous aerobic exercise was also associated with lower risk for dementia (HR 0·76, 95% CI 0·72-0·80 for walking and 0·89, 0·85-0·93 for vigorous aerobic exercise; p<0·0001 for trend for both activities) and subjective cognitive decline (RR 0·82, 95% CI 0·79-0·86 for walking and 0·89, 0·86-0·93 for vigorous aerobic exercise; p<0·0001 for trend for both activities). Additionally, being in the highest quartile of total physical activity versus the lowest quartile was associated with fewer years of age-related cognitive differences in global cognition (mean difference -1·15, 95% CI -1·69 to -0·60; p<0·0001 for trend), verbal memory (-1·27, -1·86 to -0·68; p<0·0001 for trend), and TICS score (-0·79, -1·36 to -0·23; p=0·016 for trend). Similar decreases were observed for vigorous aerobic exercise but not for walking. INTERPRETATION:Higher levels of physical activity were associated with a lower risk of dementia and better cognitive performance. These findings support physical activity as a potential strategy to promote long-term cognitive health. FUNDING:US National Institutes of Health.

Metabolomic indices summarizing diet-related metabolic responses are instrumental for examining and replicating diet–disease associations. Here we aim to identify metabolomic signatures characterizing the amounts and types of dietary carbohydrate and assess their associations with type 2 diabetes (T2D) risk. Nutritional metabolomics indices were developed using data from 1,196 healthy participants in the Lifestyle Validation Study with 7-day diet records (7DDRs). Elastic net regression within cross-validation was used to derive metabolomic indices of total carbohydrates and primary food sources. Replication was conducted using feeding menu data among 153 women from the Nutrition and Physical Activity Assessment Study. Associations with incident T2D were examined using multivariable Cox regression in 11,454 participants from the Nurses’ Health Study, Nurses’ Health Study II and Health Professionals Follow-up Study. Metabolites positively associated with total carbohydrates and added sugars mainly included glycerolipids (diacylglycerols and triglycerides), whereas glycerophospholipids (phosphatidylethanolamines and phosphatidylcholines) were inversely associated. Whole grains were linked to betaine, 3-indolepropionic acid (IPA) and hippuric acid; vegetables and legumes to IPA, N-acetylornithine and pipecolic acid; and fruits to proline-betaine and IPA. Identified metabolomic signatures showed significant correlations with a 7-day diet record-assessed diet in the Lifestyle Validation Study (Pearson r 0.33–0.65). In the Nutrition and Physical Activity Assessment Study, the metabolomic index of total carbohydrates was also significantly correlated with intake (r = 0.40). Signatures for total carbohydrates, added sugars, refined grains and potatoes were associated with higher T2D risk (HR per s.d. (95

BACKGROUND:Alcohol consumption is common behavior among US veterans, yet its impact on long-term health outcomes remains incompletely understood. OBJECTIVE:We conducted a cohort study to examine the associations between alcohol consumption versus abstention and major adverse cardiovascular events (MACE; myocardial infarction, stroke, or cardiovascular death), cancers, and total mortality. METHODS:Self-reported alcohol consumption was collected from 438,442 participants from the prospective Million Veteran Program Study (MVP 2011-2024). The outcomes included total mortality and indent cancer and MACE. RESULTS:A J-shaped association was observed between alcohol and risk of mortality (both Ps for linear trend and curvature<0.0001) and risk of MACE (P for curvature<0.0001; P for linear trend = 0.24). Compared to never drinkers, the hazard ratio (HR) for mortality was 0.86 (0.84, 0.89) for current drinkers with alcohol 0.1-30g/d, and 0.84 (0.80, 0.89) for MACE. The HR for cancer was positively associated with higher daily intake among current drinkers: 1.03 (0.99, 1.17) [0.1-30g/d], 1.06 (1.00, 1.12) [31-60g/d], 1.20 (1.12, 1.29) [61-90g/d] and 1.28 (1.12, 1.47) [>90g/d] (P for curvature =0.06, P for linear trend<0.0001). Compared to participants who reported never smoking and never drinking, the HR for head and neck cancer was 3.21 (2.17, 4.74) among current smokers with moderate alcohol consumption (females up to 14g/d and males up to 28g/d) and 5.69 (3.76, 8.62) among current smokers with heavy drinking (P for interaction=0.03). CONCLUSIONS:Among US Veterans, alcohol consumption was associated with mortality and MACE in a J-shaped pattern, with lower risk observed at moderate consumption levels compared to abstinence or heavier drinking. However, alcohol consumption demonstrates a linear dose-response relationship with cancers, with increased risks for alcohol-related cancers even at moderate consumption levels. The alcohol and head and neck cancer association was significantly exacerbated by smoking.

INTRODUCTION:Associations of adherence to and changes in Mediterranean (MedDiet) and Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diets with cognitive outcomes are unclear. METHODS:We prospectively followed 86,740 women (Nurses' Health Study, 1980-2023) and 43,500 men (Health Professionals Follow-Up Study, 1986-2023). Diet was assessed repeatedly using food frequency questionnaires. Dementia cases were identified from self-reported physician diagnoses and death records. Cognitive function was assessed by telephone tests, and subjective cognitive decline (SCD) was self-reported. RESULTS:Participants in the highest versus lowest MedDiet and MIND categories had 21% (hazard ratio [HR] = 0.79, 95% confidence interval [CI]: 0.73-0.84) and 14% (HR = 0.86, 95% CI: 0.81-0.91) lower dementia risk, respectively. Higher adherence was associated with 0.75 to 1.59 fewer years of cognitive aging, and 40% to 42% lower risk of SCD. Similar inverse associations were observed for improved adherence over 4 or 8 years. DISCUSSION:Adherence to Mediterranean and MIND diets was associated with cognitive benefits.

Importance:Evidence linking coffee and tea to cognitive health remains inconclusive, and most studies fail to differentiate caffeinated from decaffeinated coffee. Objective:To investigate associations of coffee and tea intake with dementia risk and cognitive function. Design, Setting, and Participants:Prospective cohort study that included female participants from the Nurses' Health Study (NHS; n = 86 606 with data from 1980-2023) and male participants from the Health Professionals Follow-up Study (HPFS; n = 45 215 with data from 1986-2023) who did not have cancer, Parkinson disease, or dementia at study entry (baseline) in the US. Exposures:The primary exposures were intakes of caffeinated coffee, decaffeinated coffee, and tea. Dietary intake was collected every 2 to 4 years using validated food frequency questionnaires. Main Outcomes and Measures:The primary outcome was dementia, which was identified via death records and physician diagnoses. The secondary outcomes included subjective cognitive decline assessed by a questionnaire-based score (range, 0-7; higher scores indicate greater perceived decline; cases defined as those with a score ≥3) and objective cognitive function assessed only in the NHS cohort using telephone-based neuropsychological tests such as the Telephone Interview for Cognitive Status (TICS) score (range, 0-41) and a measure of global cognition (a standardized mean z score for all 6 administered cognitive tests). Results:Among 131 821 participants (mean age at baseline, 46.2 [SD, 7.2] years in the NHS cohort and 53.8 [SD, 9.7] years in the HPFS cohort; 65.7% were female) during up to 43 years of follow-up (median, 36.8 years; IQR, 28-42 years), there were 11 033 cases of incident dementia. After adjusting for potential confounders and pooling results across cohorts, higher caffeinated coffee intake was significantly associated with lower dementia risk (141 vs 330 cases per 100 000 person-years comparing the fourth [highest] quartile of consumption with the first [lowest] quartile; hazard ratio, 0.82 [95% CI, 0.76 to 0.89]) and lower prevalence of subjective cognitive decline (7.8% vs 9.5%, respectively; prevalence ratio, 0.85 [95% CI, 0.78 to 0.93]). In the NHS cohort, higher caffeinated coffee intake was also associated with better objective cognitive performance. Compared with participants in the lowest quartile, those in the highest quartile had a higher mean TICS score (mean difference, 0.11 [95% CI, 0.01 to 0.21]) and a higher mean global cognition score (mean difference, 0.02 [95% CI, -0.01 to 0.04]); however, the association with global cognition was not statistically significant (P = .06). Higher intake of tea showed similar associations with these cognitive outcomes, whereas decaffeinated coffee intake was not associated with lower dementia risk or better cognitive performance. A dose-response analysis showed nonlinear inverse associations of caffeinated coffee and tea intake levels with dementia risk and subjective cognitive decline. The most pronounced associated differences were observed with intake of approximately 2 to 3 cups per day of caffeinated coffee or 1 to 2 cups per day of tea. Conclusions and Relevance:Greater consumption of caffeinated coffee and tea was associated with lower risk of dementia and modestly better cognitive function, with the most pronounced association at moderate intake levels.

Medical nutritional therapy, an evidence-based application of the nutrition care process guided by a registered dietitian nutritionist, is an integral part of diabetes management, with emerging evidence suggesting distinct nutritional requirements in this population. A thorough review of the existing literature reveals an imperative to address the specific requirements for vitamins and minerals in this population. Current guidelines have given limited attention to micronutrients, despite the higher prevalence of deficiencies and the altered patterns of association between serum micronutrient concentrations and multiple health outcomes among individuals with type 2 diabetes (T2D). To enhance diabetes management, an international multidisciplinary panel of 20 experts from 12 countries participated in a modified Delphi process, which was informed by a narrative review conducted by the research team, to reach consensus on 18 statements, encompassing 11 nutrient-specific recommendations and 7 statements outlining future directions in diabetes nutrition therapy research. The plan for this consensus has been registered on the Practice Guideline Registration for Transparency (registration number: PREPARE-2025CN1178). The expert panel proposed potential target serum concentrations, screening strategies, and micronutrient supplementation for people with T2D and that personalized nutritional strategies integrating individual characteristics, genetic information, and gut microbiota represent key areas for future research.

Background The timing of exposure to diet across the lifespan may be critical in the development of T2D. However, no previous study has deciphered the influence of dietary insulinemic and inflammatory potential on the risk of T2D across the lifespan from a life course perspective. Objective This study aimed to evaluate the associations of dietary insulinemic and inflammatory potential with the risk of T2D from a life course perspective. Design This was a prospective cohort study. Participants and setting Data from 40,135 eligible, female participants in the Nurses’ Health Study II were analyzed. Adulthood diet was assessed quadrennially since 1991 using 131-item food frequency questionnaires (FFQ), and adolescent diet was recalled in 1997 using a 124-item high-school FFQ. The main exposures were empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores across different life stages (adolescence, premenopausal adulthood, postmenopausal adulthood) and changes and cumulatively over the lifetime. Main outcome measures The main outcome was incident T2D. Statistical analyses performed Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results Higher EDIH and EDIP scores (highest vs lowest quintiles) were associated with increased lifetime risk of T2D as a lifetime average (HR, 95%CI: 2.72, 2.38-3.11 and 2.04, 1.81-2.30), during premenopausal adulthood (3.18, 2.52-4.01 and 2.31, 1.88-2.82), and postmenopausal adulthood (2.67, 2.15-3.33 and 1.70, 1.41-2.05), but not during adolescence (1.07, 0.95-1.20 and 1.10, 0.98-1.24). The HR, 95%CI associated with higher lifetime averages for both EDIH and EDIP (vs. low lifetime averages for both, based on tertiles) was 2.64 (2.32-3.01). Individuals with high adulthood EDIH or EDIP had similar magnitudes of lifetime risk elevation, regardless of their adolescent EDIH and EDIP status. Adolescent EDIH and EDIP were associated with a slightly increased premenopausal T2D risk (1.24, 1.02-1.51, and 1.24, 1.02-1.50). In additional analyses estimating the time window during which adulthood dietary insulinemic and inflammatory potential influences T2D risk, higher adulthood EDIH or EDIP was associated with an increased risk of T2D with a very short time lag. Conclusions Over the life course in women, high dietary insulinemic and inflammatory potential in both premenopausal and postmenopausal adulthood were independently associated with a substantially increased lifetime risk of T2D. Adulthood offers the most critical time window for dietary interventions to reduce lifetime T2D risk, though adolescent diet may influence the risk of premenopausal T2D.

ABSTRACT Background Many epidemiological studies rely on dietary exposures taken from baseline only. This limits our understanding of diet-disease associations because it requires assuming a level of temporal stability, either by individuals or dietary pattern composition. Objectives This study aimed to evaluate these analytic assumptions of pattern structure consistency and baseline adherence using a cohort of US Black women with repeated measures of food frequency questionnaires (FFQ). Methods Data from 6151 Black women aged 21-69 from the Black Women’s Health Study with complete FFQ data in 1995, 2001, 2013, and 2021 were evaluated for temporal stability. Baseline dietary patterns were derived using an overfitted latent class model. Parameter estimates from the baseline model were then applied to subsequent waves to track individual transitions between existing patterns. Dietary patterns were also derived at each time point using an overfitted latent class model and assessed for changes in pattern composition over time. Results Five baseline dietary patterns were identified in 1995. Only 18% of participants remained in the same baseline dietary pattern across all four time points, while all others transitioned to a different baseline-derived pattern. Dietary patterns derived independently at subsequent time points, yielded a different number of dietary patterns at each time point (2001: 6 patterns, 2013: 5 patterns, 2021: 4 patterns). Correlation strength of subsequent derived patterns and baseline patterns significantly weakened in strength after 2001 (40% pairings > 0.5), with no patterns correlated greater than 0.5 in 2021. Conclusion Prospective studies that rely on baseline dietary exposure data cannot assume stability of pattern composition or individual pattern adherence over time, as it ignores changes in dietary habits and may bias our understanding of the diet-disease pathway.

BACKGROUND:In 2019, the EAT-Lancet commission defined a "planetary health diet", a combination of food groups and ranges of food intakes that would simultaneously optimize human health and environmental sustainability. We aimed to evaluate adherence to the Planetary Health Diet Index (PHDI) and breast cancer incidence. METHODS:We followed 68,254 participants in the Nurses' Health Study (NHS; 1986-2018) and 93,283 in the Nurses' Health Study II (NHSII; 1991-2019). The PHDI was calculated every 4 y using a validated, semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS:During 4,182,897 person-years of follow-up, we documented 10,378 invasive breast cancer cases. Women in the highest, compared to lowest, PHDI quintile (Q) were at lower breast cancer risk (HRQ5 vs. Q1 = 0.89; 95% CI: 0.84, 0.95; P-trend<0.01) even after adjusting for weight change. Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association was observed for estrogen receptor (ER) negative tumors (HRQ5 vs. Q1 = 0.79; 95% CI: 0.66, 0.93; P-trend = 0.01). CONCLUSIONS:Adhering to a diet that supports both human and planetary health was associated with lower breast cancer risk, particularly ER-negative tumors. Strategies to reduce breast cancer incidence should emphasize the win-win opportunities for a high planetary health diet.

BACKGROUND:Numerous carbohydrate quality metrics (CQMs) have been suggested, yet the optimal one(s) associated with the lowest type 2 diabetes (T2D) risk remains unknown. OBJECTIVES:We aimed to systematically compare 23 CQMs with T2D risk, identify the 5 strongest associations, propose an alternate Carbohydrate Quality Index (aCQI), and compare it with the existing CQI regarding T2D risk and cardiometabolic biomarkers. METHODS:We included participants of 3 prospective cohort studies [Nurses' Health Study I (1984-2020) and II (1991-2019), and Health Professionals Follow-up Study (1986-2020)], who were free of cancer, diabetes, and cardiovascular disease. Our primary outcome was incident T2D. We examined 13 plasma biomarkers in relation to CQIs among a subset. RESULTS:During 5,628,955 person-years of follow-up among 213,704 adults, 22,351 cases of incident T2D were ascertained. In multivariable-adjusted models, comparing Q5 to Q1, intakes of cereal fiber [relative risk (RR): 0.77 (0.74-0.81)], whole-fruit carbohydrates [RR: 0.80 (0.76-0.84)], glycemic index [RR: 1.20 (1.14-1.26)], sugar from sugar-sweetened beverages [RR: 1.22 (1.17-1.28)], and whole-grain carbohydrates [RR: 0.86 (0.82-0.91)] had the strongest associations with T2D risk. The aCQI [RR: 0.71 (0.68-0.75)], comprising these variables, had a larger magnitude of association with T2D risk than the original CQI [RR: 0.82 (0.79-0.87)], which included total fiber intake, glycemic index, the ratios of whole to total grains, and solid to total carbohydrates. The aCQI had significant associations with a larger percentage of differences in cardiometabolic biomarker concentrations, such as C-peptide, leptin, and LDL cholesterol, than the CQI (all P-trend ≤ 0.001). CONCLUSIONS:The novel aCQI, comprised carbohydrates from whole fruits, whole grains, sugar-sweetened beverages, cereal fiber, and glycemic index, was more strongly associated with risk of T2D and cardiometabolic biomarkers than its individual components or the existing CQI, necessitating further research.

Regression calibration is a widely used method for correcting bias in regression coefficient estimates caused by measurement error in continuous exposures. In nutritional epidemiology, recent studies often use nutrient-derived biomarkers to calibrate true dietary intakes, which are typically assessed through small feeding studies or weighed dietary records. However, biomarkers may themselves lie on the causal pathway between intake and outcome, violating the surrogacy assumption that underpins the validity of regression calibration. We evaluate regression calibration-based methods that have been applied or proposed for calibrating dietary intake using biomarkers, focusing on their validity and relative efficiency. Our assessment combines analytic bias quantification, simulation studies, and a real-data application. Two approaches are generally valid when using mediators to calibrate the true exposure: (1) the expanded calibration method, which recovers the total effect via the product method from mediation analysis, and (2) the two-stage calibration method. In simulations reflecting realistic scenarios, the expanded calibration method demonstrated superior efficiency for a continuous outcome. Finally, we show that estimating the effect of dietary intake using a calibrated biomarker is valid when the mean biomarker calibration model contains a linear term in true intake with coefficient one, possibly along with additional covariates.

Background: Whether habitually consuming artificially sweetened beverages (ASBs) in place of sugar-sweetened beverages (SSBs) is associated with weight changes is unclear. Objectives: To evaluate the association of increasing ASBs or water, as SSBs replacements, with changes in weight/body mass index (BMI). Methods: We analyzed data from the Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Adults aged 26-65 y were followed for 24-32 y with biennial questionnaires updating medical, lifestyle, and anthropometric data. Multivariable-adjusted linear models estimated associations between changes in ASB intake, substitution of SSBs with ASBs or water, and 4-y weight and BMI changes. Latent class growth models and multinomial logistic models estimated the odds of weight-trajectory membership based on beverage intake. Results: Among 143,409 participants (median follow-up 28 y), the mean weight gain per 4-y interval was 1.3 kg (5th-95th percentile:- 6.3 to 9.1 kg). Each 3-serving/wk increase in ASB was associated with-0.18 kg weight change [95% confidence interval (CI): -0.26 kg, -0.11 kg] and-0.06 kg/m2 BMI change (95% CI: -0.09 kg/m2, -0.03 kg/m2) over 4-y intervals, with stronger inverse associations among adults with overweight/obesity and higher SSB intake. Replacing 3 SSB servings/wk with ASB was associated with lower weight (-1.39 kg, 95% CI: -1.50 kg, -1.28 kg) and BMI gains (-0.50 kg/ m 2 95% CI: -0.54 kg/m2, -0.45 kg/m2), with larger SSB-to-ASB replacements associated with progressively less gains. Similar estimates were observed when replacing SSB with water (-1.39 kg, 95% CI: -1.48 kg, -1.30 kg and-0.49 kg/m2, 95% CI: -0.53 kg/m2, -0.46 kg/m2). Replacing ASB with water was associated with modest reductions in weight (-0.11 kg, 95% CI: -0.19 kg, -0.03 kg) and BMI gains (-0.04 kg/m2, 95% CI: -0.08 kg/m2, -0.01 kg/ m 2 ). Higher ASB or water intake were inversely associated with unhealthy weight trajectories. Conclusions: Increases in ASB intake were inversely associated with weight/BMI gains over time, particularly among adults with overweight/obesity and higher SSB intake. Replacing SSBs with ASBs-or ideally water-was associated with decreases in weight/BMI changes in a dose-dependent manner.

ABSTRACT Background Several breast cancer (BC) risk prediction models have been developed to provide personal risk assessments. Though individually validated, their performance has not been systematically evaluated across a wide range of populations or ages. Methods We harmonized individual-level baseline questionnaire data and incident BC diagnoses from 21 cohorts from North America, Europe, and Australia participating in the Breast Cancer Risk Prediction Project. Five-year absolute risk of invasive BC was estimated for five established risk prediction models using classical risk factors only. Discrimination was evaluated by area under the curve (AUC). Calibration was assessed using average and risk-decile specific expected to observed (E/O) ratios. Performance metrics were meta-analyzed across cohorts and models. Metaregression tested associations between cohort characteristics and performance metrics. Results This analysis included 1,595,977 women aged 20-75 years, enrolled in studies between 1976-2015, with 19,062 (1.2%) invasive BC cases ascertained within 5 years from exposure assessment. Age-adjusted AUCs were similar across models and cohorts (pooled AUCs by model: 0.57-0.58), while E/O ratios varied substantially (pooled E/O ratios by model: 0.83-1.25). Overestimation was common among predicted high-risk individuals (>3%). No appreciable differences in model performance by cohort age, birth year, race, and variable missingness emerged. Calibration improved after assigning race-specific incidence rates. Conclusion Existing BC risk prediction models provided similar risk discrimination across multiple cohorts, although there was overestimation of risk for high-risk individuals. Performance variation across cohorts was not driven by specific characteristics, which supports development of a unified risk model for diverse populations that leverages appropriate incidence rates. Key messages When using classical risk factor components of existing risk prediction models, we found similar discriminatory ability of models across diverse cohorts. Aside from underlying cancer incidence rate, which heavily influenced calibration, no cohort-specific characteristics were consistently associated with model performance. Risk was underestimated at lower predicted risk deciles and overestimated at higher predicted risk deciles, indicating a need to improve model fit by integrating more complex risk-factor relationships.

We assessed associations of total and group-specific ultra-processed food (UPF) intake with type 2 diabetes (T2D) incidence in the Hispanic Community Health Study/Study of Latinos, overall and with a priori stratification by Hispanic/Latino heritage, US nativity, BMI categories, and diet quality measured by tertiles of the Alternative Healthy Eating Index (AHEI). Data entailed 8010 adults, completing follow-up (2014-17), and without baseline (2008-11) diabetes, cardiovascular disease, and/or cancer (mean follow-up: 5.8 years). Baseline 24-h dietary recalls and food propensity questionnaires assessed UPF intakes (% of diet weight) defined by the Nova framework. Self-report, anti-diabetes medications, and standard biomarker thresholds defined incident T2D. Poisson models adjusted for sociodemographic, acculturation, lifestyle, energy intake, and diabetes family history variables estimated incidence rate ratios (95% CI) of T2D per 10-percentage-point increase in total UPF intake and 1-SD increase in inverse normal transformed UPF group intakes. UPF constituted 19.8% of diet weight. Each 10-percentage-point increase in UPF was associated with 1.16 (1.01-1.34) higher T2D incidence overall (1273 cases). In stratified analyses, associations remained only for Puerto Ricans (1.22; 1.01-1.47), US-born persons (1.26; 1.03-1.54), and those with overweight/obesity (1.16; 1.01-1.35). Regarding UPF groups, artificially-sweetened beverages and processed poultry/fish were associated with a higher incidence of T2D in the overall sample. Among Puerto Ricans, US-born participants, and persons in the lowest AHEI tertile, ultra-processed bread/cereals, soft drinks, poultry/fish, and hard liquors were associated with a higher incidence of T2D, whereas ultra-processed sweet snacks, desserts, and spreads and savory snacks were associated with lower incidence. Limiting UPF is associated with lower T2D incidence among US Hispanics/Latinos, particularly Puerto Rican and US-born. Attention to group-specific UPF intake is warranted.

BACKGROUND/OBJECTIVE:Studies show an association between elevated blood pressure, obesity, and insulin resistance with a higher risk of developing diabetes. As sodium is closely linked to elevated blood pressure and hypertension, and potassium is a counterbalancing nutrient to sodium, this study examines the association between intake of sodium, potassium, and sodium: potassium (Na:K) ratio and the incidence of diabetes. DESIGN SETTING AND PARTICIPANTS:Retrospective data analysis of dietary intake measured by a validated food frequency questionnaire in a prospective cohort of veterans participating in the Million Veteran Program (MVP) between 2011 and 2020, who were free of diabetes at baseline. MAIN OUTCOME MEASUREMENT:The main outcome is clinically diagnosed diabetes defined by phenotyping algorithms applied to electronic health records. RESULTS:In this study of 198,049 veterans (mean age: 63.8 ± 13.1 years, 89 % male), 7260 were diagnosed with diabetes over a mean follow-up of 4.3 years. The mean sodium intake was 1218 mg/day. A higher sodium intake was associated with an 11 % higher rate of developing diabetes (hazard ratio, HR) comparing extreme quintiles: 1.11, 95 % CI: 1.03-1.20). The average daily potassium intake was 2589 mg and the highest quintile of potassium intake was associated with a 13 % lower rate of diabetes (HR: 0.87, 95 % CI: 0.81, 0.94) compared to the lowest quintile of potassium. Highest quintile of Na:K ratio was associated with a 21 % higher rate for diabetes (HR: 1.21, 95% CI: 1.12, 1.30). The pattern of associations between Na:K ratio and diabetes closely followed the pattern of dietary sodium intake and diabetes associations. CONCLUSION:A higher sodium intake and a higher Na:K ratio were associated with a higher risk of diabetes in this large cohort of veterans. These findings may be applied in future work to identify personalized lifestyle and dietary supports to prevent and treat T2DM.