Showing papers by "Frank B. Hu published in 2023"

Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality.

Abstract: Importance The current Dietary Guidelines for Americans recommend multiple healthy eating patterns. However, few studies have examined the associations of adherence to different dietary patterns with long-term risk of total and cause-specific mortality. Objective To examine the associations of dietary scores for 4 healthy eating patterns with risk of total and cause-specific mortality. Design, Setting, and Participants This prospective cohort study included initially healthy women from the Nurses' Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020). Exposures Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED) score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). Main Outcomes and Measures The main outcomes were total and cause-specific mortality overall and stratified by race and ethnicity and other potential risk factors. Results The final study sample included 75 230 women from the NHS (mean [SD] baseline age, 50.2 [7.2] years) and 44 085 men from the HPFS (mean [SD] baseline age, 53.3 [9.6] years). During a total of 3 559 056 person-years of follow-up, 31 263 women and 22 900 men died. When comparing the highest with the lowest quintiles, the pooled multivariable-adjusted HRs of total mortality were 0.81 (95% CI, 0.79-0.84) for HEI-2015, 0.82 (95% CI, 0.79-0.84) for AMED score, 0.86 (95% CI, 0.83-0.89) for HPDI, and 0.80 (95% CI, 0.77-0.82) for AHEI (P < .001 for trend for all). All dietary scores were significantly inversely associated with death from cardiovascular disease, cancer, and respiratory disease. The AMED score and AHEI were inversely associated with mortality from neurodegenerative disease. The inverse associations between these scores and risk of mortality were consistent in different racial and ethnic groups, including Hispanic, non-Hispanic Black, and non-Hispanic White individuals. Conclusions and Relevance In this cohort study of 2 large prospective cohorts with up to 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality. These findings support the recommendations of Dietary Guidelines for Americans that multiple healthy eating patterns can be adapted to individual food traditions and preferences.

Beverage consumption and mortality among adults with type 2 diabetes: prospective cohort study

Abstract: Abstract Objective To investigate the intake of specific types of beverages in relation to mortality and cardiovascular disease (CVD) outcomes among adults with type 2 diabetes. Design Prospective cohort study. Setting Health professionals in the United States. Participants 15 486 men and women with a diagnosis of type 2 diabetes at baseline and during follow-up (Nurses’ Health Study: 1980-2018; and Health Professionals Follow-Up Study: 1986-2018). Beverage consumption was assessed using a validated food frequency questionnaire and updated every two to four years. Main outcome measures The main outcome was all cause mortality. Secondary outcomes were CVD incidence and mortality. Results During an average of 18.5 years of follow-up, 3447 (22.3%) participants with incident CVD and 7638 (49.3%) deaths were documented. After multivariable adjustment, when comparing the categories of lowest intake of beverages with the highest intake, the pooled hazard ratios for all cause mortality were 1.20 (95% confidence interval 1.04 to 1.37) for sugar sweetened beverages (SSBs), 0.96 (0.86 to 1.07) for artificially sweetened beverages (ASBs), 0.98 (0.90 to 1.06) for fruit juice, 0.74 (0.63 to 0.86) for coffee, 0.79 (0.71 to 0.89) for tea, 0.77 (0.70 to 0.85) for plain water, 0.88 (0.80 to 0.96) for low fat milk, and 1.20 (0.99 to 1.44) for full fat milk. Similar associations were observed between the individual beverages and CVD incidence and mortality. In particular, SSB intake was associated with a higher risk of incident CVD (hazard ratio 1.25, 95% confidence interval 1.03 to 1.51) and CVD mortality (1.29, 1.02 to 1.63), whereas significant inverse associations were observed between intake of coffee and low fat milk and CVD incidence. Additionally, compared with those who did not change their consumption of coffee in the period after a diabetes diagnosis, a lower all cause mortality was observed in those who increased their consumption of coffee. A similar pattern of association with all cause mortality was also observed for tea, and low fat milk. Replacing SSBs with ABSs was significantly associated with lower all cause mortality and CVD mortality, and replacing SSBs, ASBs, fruit juice, or full fat milk with coffee, tea, or plain water was consistently associated with lower all cause mortality. Conclusions Individual beverages showed divergent associations with all cause mortality and CVD outcomes among adults with type 2 diabetes. Higher intake of SSBs was associated with higher all cause mortality and CVD incidence and mortality, whereas intakes of coffee, tea, plain water, and low fat milk were inversely associated with all cause mortality. These findings emphasize the potential role of healthy choices of beverages in managing the risk of CVD and premature death overall in adults with type 2 diabetes.

Nuts in the Prevention and Management of Type 2 Diabetes

Abstract: Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.

Ultra-Processed Food Consumption and Risk of Type 2 Diabetes: Three Large Prospective U.S. Cohort Studies.

Abstract: OBJECTIVE We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality. RESEARCH DESIGN AND METHODS We included 71,871 women from the Nurses' Health Study, 87,918 women from the Nurses' Health Study II, and 38,847 men from the Health Professional Follow-Up Study. Diet was assessed using food frequency questionnaires and UPF was categorized per the NOVA classification. Associations of total and subgroups of UPF with T2D were assessed using Cox proportional hazards models. We subsequently conducted a meta-analysis of prospective cohort studies on total UPF and T2D risk, and assessed meta-evidence quality using the NutriGrade scoring system. RESULTS Among the U.S. cohorts (5,187,678 person-years; n = 19,503 T2D cases), the hazard ratio for T2D comparing extreme quintiles of total UPF intake (percentage of grams per day) was 1.46 (95% CI 1.39-1.54). Among subgroups, refined breads; sauces, spreads, and condiments; artificially and sugar-sweetened beverages; animal-based products; and ready-to-eat mixed dishes were associated with higher T2D risk. Cereals; dark and whole-grain breads; packaged sweet and savory snacks; fruit-based products; and yogurt and dairy-based desserts were associated with lower T2D risk. In the meta-analysis (n = 415,554 participants; n = 21,932 T2D cases), each 10% increment in total UPF was associated with a 12% (95% CI 10%-13%) higher risk. Per NutriGrade, high-quality evidence supports this relationship. CONCLUSION High-quality meta-evidence shows that total UPF consumption is associated with higher T2D risk. However, some UPF subgroups were associated with lower risk in the U.S. cohorts.

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study.

Abstract: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.ISRCTN35739639.

Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.

Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.

Abstract MP07: Changes in Weight From Sugar- or Artificially-Sweetened Beverages or Water Intake in a Prospective Cohort

Abstract: Background: It is still unclear if sustained intake of artificially sweetened beverages (ASB) in lieu of sugar-sweetened beverages (SSB) is associated with long-term weight reduction or maintenance. This study aimed to evaluate the long-term changes in weight and BMI in relation to changes in ASB intake, and to estimate the effects of replacing SSB with ASB or water on body weight. Hypothesis: Habitual ASB intake is unrelated to weight or BMI changes. The modeled substitutions are expected to show a reduction in weight and BMI, larger for water than for ASB. Methods: We used data from the Nurses' Health Study I, a prospective cohort study conducted among female US nurses aged 39 to 65y at enrolment and assessed every four years from 1986 to 2010. Food-frequency questionnaires evaluated usual dietary intake including beverages (in 12 oz servings/day). Self-administered questionnaires collected lifestyle and anthropometric information. We excluded participants with any major disease at baseline (e.g., diabetes, cancer, cardiovascular disease), and censored those reaching 65 years during follow-up. Pregnant or lactating women were not considered during these periods. We evaluated the association between changes in ASB intake with changes in weight and BMI using generalized estimating models adjusting for multiple dietary and lifestyle risk factors. Substitution models assessed how replacing SSB with ASB, SSB with water, or ASB with water relates to weight and BMI changes, adjusting for the same covariates. Results: Among 51,805 participants, 64.6% consumed ASB at baseline averaging 0.25 ± 0.53 servings/day. Over 4-year follow-up intervals, a one-serving/day increase of ASB was associated with an estimated weight change of -0.06 kg (95% CI: -0.11, -0.02) and BMI change of -0.02 kg/m 2 (95% CI: -0.04, -0.01). Substituting SSB with ASB was associated with -0.37 kg change in weight (95% CI: -0.41, -0.33) and -0.14 kg/m 2 in BMI (95% CI: -0.17, -0.11). Similar estimates were observed when replacing SSB with water ( β =-0.35 kg, 95% CI: -0.41, -0.30 for weight and β =-0.13, kg/m 2 , 95% CI: -0.15, -0.11 for BMI). Substituting ASB with water was not associated with changes in weight ( β =-0.004 kg, 95% CI: -0.05, 0.04) or BMI ( β =-0.0002 kg/m 2 , 95% CI: -0.02, 0.02). Conclusion: A long-term daily increase in ASB intake was not associated with greater weight gain in US women. Replacing SSB with ASB was associated with significantly less weight gain, likely by reducing energy intake. Change in water was not associated with weight changes, suggesting it may help sustain weight maintenance when replacing SSB. Future studies should evaluate the roles of changes in intakes of water, ASB, and SSB in relation to changes in other weight- and metabolically-related outcomes in diverse populations of both sexes.

1327-P: The Association between Adherence to Mediterranean Dietary Pattern and Nephropathy in Long-Duration Type 1 Diabetes

Abstract: Vascular complications contribute to the high morbidity and mortality in type 1 diabetes (T1D), necessitating a search for new therapeutic measures. The Alternative Mediterranean diet score (aMED), high in vegetable, fruits, legumes, whole grains, nuts, and low in red and processed meat and uses olive oil as the main fat source, has been shown to improve glycemic control and reduce cardiovascular disease (CVD) risk in type 2 diabetes, but has not been examined for relationships to vascular complications in T1D. We examined the cross-sectional relationships between aMed adherence and vascular complications among 645 individuals of the Joslin 50-year Medalist study having T1D > 50 years and food frequency histories captured. In multivariable logistic regression models adjusting for age and sex, a higher adherence to a Mediterranean diet was associated with a 17% reduced odds of diabetic nephropathy (DN, eGFR <60 ml/min/1.73m2) [OR 0.83, 95% Cl 0.72-0.95, p=0.008], and this remained significant (p<0.05) after further adjustments for HbA1c, diabetes duration, lipids and blood pressure. There were no significant associations between aMed and CVD, diabetic retinopathy or neuropathy. Among the specific aMED components, higher intake of nuts, higher ratio of monounsaturated fat to saturated fat and lower intake of red and processed meats were all associated with significantly (p<0.05) reduced odds of DN. Triglycerides, HDL and albumin-creatinine ratio (ACR) were significant effect modifiers (p for interaction <0.05) such that, more DN-protective effects of aMed were observed among those with higher triglycerides, lower HDL, and higher ACR. To conclude, our findings suggest that greater adherence to a Mediterranean diet in individuals with long duration T1D is associated with lower risk of DN, independent of traditional risk factors. Further studies are warranted to validate its potential as an effective therapeutic approach against DN in people with T1D. A.Hayes: None. G.L.King: Research Support; Janssen Research & Development, LLC. H.Shah: None. S.Jangolla: None. J.Gauthier: None. N.A.Ziemniak: None. I.Wu: None. K.Lau: None. A.Adam: None. F.Hu: None. F.K.Tabung: None. Nunnally Foundation Inc.; Thomas J. Beatson, Jr. Foundation

Nuts, Energy Balance and Body Weight

Abstract: Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.

Dietary Inflammatory and Insulinemic Potentials, Plasma Metabolome and Risk of Colorectal Cancer

Abstract: The inflammatory and insulinemic potentials of diets have been associated with colorectal cancer risk. However, it is unknown whether the plasma metabolite profiles related to inflammatory diets, or to insulinemic diets, underlie this association. The aim of this study was to evaluate the association between metabolomic profile scores related to the food-based empirical dietary inflammatory patterns (EDIP), the empirical dietary index for hyperinsulinemia (EDIH), and plasma inflammation (CRP, IL-6, TNFα-R2, adiponectin) and insulin (C-peptide) biomarkers, and colorectal cancer risk. Elastic net regression was used to derive three metabolomic profile scores for each dietary pattern among 6840 participants from the Nurses’ Health Study and Health Professionals Follow-up Study, and associations with CRC risk were examined using multivariable-adjusted logistic regression, in a case-control study of 524 matched pairs nested in both cohorts. Among 186 known metabolites, 27 were significantly associated with both the EDIP and inflammatory biomarkers, and 21 were significantly associated with both the EDIH and C-peptide. In men, odds ratios (ORs) of colorectal cancer, per 1 standard deviation (SD) increment in metabolomic score, were 1.91 (1.31–2.78) for the common EDIP and inflammatory-biomarker metabolome, 1.12 (0.78–1.60) for EDIP-only metabolome, and 1.65 (1.16–2.36) for the inflammatory-biomarkers-only metabolome. However, no association was found for EDIH-only, C-peptide-only, and the common metabolomic signatures in men. Moreover, the metabolomic signatures were not associated with colorectal cancer risk among women. Metabolomic profiles reflecting pro-inflammatory diets and inflammation biomarkers were associated with colorectal cancer risk in men, while no association was found in women. Larger studies are needed to confirm our findings.

A South Asian Mediterranean‐style diet is associated with favorable adiposity measures and lower diabetes risk: The MASALA cohort

Abstract: The Mediterranean diet is associated with lower risks for type 2 diabetes (T2D) and cardiovascular disease in certain populations, although data among diverse groups are limited. This study evaluated cross‐sectional and prospective associations between a novel South Asian Mediterranean‐style (SAM) diet and cardiometabolic risk among US South Asian individuals.

Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

Abstract: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects.This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort.The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause.In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations.Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

Abstract P418: Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease and Mortality in Adults With Type 2 Diabetes

Abstract: Background: The potential health effects of dietary glutamine and glutamate have been studied in healthy populations, but evidence among individuals with type 2 diabetes (T2D) who have altered macronutrient metabolism and elevated cardiovascular disease (CVD) risk is limited. Objectives: We aimed to examine dietary glutamine and glutamate in relation to subsequent risk of CVD, including coronary heart disease and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods: We prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years since baseline. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. Results: During 196,955 and 225,371person-years of follow-up in participants with T2D, there were 2,927 incident CVD cases and 4,898 deaths, respectively. Higher intake of glutamine was associated with lower risk of incident CVD, total mortality and CVD mortality: comparing extreme quintiles, the HRs (95%CIs) were 0.88 (0.77, 0.99), 0.85 (0.77, 0.94), and 0.82 (0.69, 0.98), respectively (all P trend <0.05). In contrast, higher intake of glutamate was associated with higher risk of incident CVD, total mortality, and CVD mortality; the HRs were 1.30 (1.15, 1.46), 1.19 (1.08, 1.31), and 1.42 (1.21, 1.67), respectively (all P trend <0.05). Furthermore, comparing extreme quintiles, higher dietary glutamine-to-glutamate ratio was associated with lower risk of CVD incidence (0.84 (0.75, 0.95)), total mortality (0.83 (0.76, 0.91)), and CVD mortality (0.69 (0.59, 0.80)). In addition, compared with participants without increment in glutamine-to-glutamate ratio from pre- to post-diabetes diagnosis, those who increased the ratio had a 15% (3%, 25%) lower CVD mortality. Conclusions: In patients with T2D, dietary glutamine and glutamate demonstrated divergent associations with CVD incidence and mortality, and higher dietary glutamine-to-glutamate ratio was significantly associated with lower CVD incidence and mortality. These data suggest a potential critical role of these two amino acids in the etiology of cardiometabolic diseases and early deaths also among adults with T2D.

Toward healthy and sustainable diets for the 21st century: Importance of sociocultural and economic considerations

Abstract: Four years after the EAT-Lancet landmark report, worldwide movements call for action to reorient food systems to healthy diets that respect planetary boundaries. Since dietary habits are inherently local and personal, any shift toward healthy and sustainable diets going against this identity will have an uphill road. Therefore, research should address the tension between the local and global nature of the biophysical (health, environment) and social dimensions (culture, economy). Advancing the food system transformation to healthy, sustainable diets transcends the personal control of engaging consumers. The challenge for science is to scale-up, to become more interdisciplinary, and to engage with policymakers and food system actors. This will provide the evidential basis to shift from the current narrative of price, convenience, and taste to one of health, sustainability, and equity. The breaches of planetary boundaries and the environmental and health costs of the food system can no longer be considered externalities. However, conflicting interests and traditions frustrate effective changes in the human-made food system. Public and private stakeholders must embrace social inclusiveness and include the role and accountability of all food system actors from the microlevel to the macrolevel. To achieve this food transformation, a new “social contract,” led by governments, is needed to redefine the economic and regulatory power balance between consumers and (inter)national food system actors.

Abstract P214: The Portfolio Dietary Pattern and Risk of Cardiovascular Disease in US Adults

Abstract: Introduction: The plant-based portfolio dietary pattern includes recognized cholesterol-lowering foods shown to improve several cardiovascular disease (CVD) risk factors in clinical trials. Epidemiological evidence on the association between longer-term adherence to the portfolio dietary pattern and CVD risk remains more limited. Objective: To examine whether the portfolio dietary pattern is associated with the risk of total CVD, coronary heart disease (CHD, including myocardial infarction and fatal coronary deaths), and stroke. Methods: Participants included 73,925 women in the Nurses’ Health Study (NHS) (1984-2014), 92,354 women in the NHS2 (1991-2017) and 43,970 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) without CVD and cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every four years using a portfolio diet score (PDS) which positively ranks plant protein (soy & pulses), nuts, viscous fiber sources, phytosterols (mg/day) and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and dietary cholesterol. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for covariates. Results: During up to 30 years of follow-up, 16,917 incident CVD cases, including 10,666 CHD cases and 6,473 stroke cases, were documented. After multivariable adjustment of lifestyle and other dietary factors, comparing the highest to the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled HR: 0.84; 95% CI: 0.80-0.89, P trend<0.001), CHD (pooled HR: 0.82; 95% CI: 0.76-0.87, P trend<0.001) and stroke (pooled HR: 0.88; 95% CI: 0.81-0.97, P trend=0.001). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR: 0.91; 95% CI: 0.88-0.93), CHD (pooled HR: 0.89; 95% CI: 0.86-0.92) and stroke (pooled HR: 0.93; 95% CI: 0.89-0.97). Results remained largely consistent across sensitivity and subgroup analyses. Conclusions: Greater adherence to the portfolio dietary pattern was consistently associated with lower risk of CVD, including CHD and stroke, in three large prospective cohorts of U.S. men and women.

Low-Carbohydrate Diet Scores and Mortality Among Adults With Incident Type 2 Diabetes.

Abstract: OBJECTIVE The current study aims to prospectively examine the association between postdiagnosis low-carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D). RSEARCH DESIGN AND METHODS Among participants with incident diabetes identified in the Nurses' Health Study and Health Professionals Follow-up Study, an overall total LCD score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy LCDS (ULCDS) were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox models were used to assess the association between the LCDS and mortality. RESULTS Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10-point increment of postdiagnosis LCDS were 0.87 (0.82, 0.92) for TLCDS, 0.76 (0.71, 0.82) for VLCDS, and 0.78 (0.73, 0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10-point increase of TLCDS, VLCDS, and HLCDS from prediagnosis to postdiagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. CONCLUSIONS Among people with T2D, greater adherence to LCD patterns that emphasize high-quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality.

Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes

Abstract: Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, >24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, >14 y: p for trend <0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: <23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.

Abstract P221: Intake of Ultra-Processed Foods in Relation to Cardiovascular Disease Incidence in US Men and Women With Diabetes Mellitus

Abstract: Introduction: Recent evidence suggests that intake of ultra-processed foods (UPF) is related to unfavorable cardio-metabolic risk profiles among generally healthy populations. However, evidence on the relationship between UPF intake and cardiovascular disease (CVD) among patients with type 2 diabetes (T2D) is lacking. Hypothesis: We assessed the hypothesis that higher intake of dietary UPF is associated with higher risks of CVD among individuals with T2D. Methods: We prospectively followed 13,272 men and women participating in the Health Professionals Follow-Up Study (HPFS) and Nurses’ Health Study (NHS) with T2D at baseline and during follow-up (HPFS: 1986-2018; NHS: 1980-2014). Diet was repeatedly assessed using validated food frequency questionnaires every 2-4 years. UPF were categorized according to the Nova classification. CVD was defined as fatal and non-fatal coronary heart disease (CHD) (including nonfatal myocardial infarction, coronary artery bypass graft surgery, and coronary angioplasty and stent) and fatal and non-fatal stroke. Associations of UPF consumption with risks of CVD were assessed using Cox regression. Results: During 165,761 person-years of follow-up, 1,826 total CHD and 529 total stroke were identified and confirmed. After adjusting for demographics, lifestyle, medical history, dietary factors, and diabetes medication use, higher total intake of UPF was associated with higher risk of CHD. The multivariable-adjusted HRs (95% CIs) were 1.20 (1.02, 1.43) ( P trend = 0.03) when comparing the highest and lowest quintiles (Q5 vs. Q1) or 1.03 (1.01, 1.04) for each 1 serving/day increment of UPF. No association between UPF intake and risk of stroke was observed (Q5 vs. Q1: 0.92 (0.67, 1.24)). These results were consistent across subgroups in analyses stratified by age, sex, BMI, diet quality, physical activity, smoking, diabetes medication use, or diabetes duration. In addition, compared with participants who had a stable or decreased consumption of UPF (≤0 change in UPF) from pre- to post-diabetes diagnosis, participants who increased consumption of UPF (>0 increment of UPF intake) after diabetes diagnosis had a 15% (1%, 31%) higher risk of CHD. Conclusions: Among participants with T2D, higher dietary UPF consumption was associated with a higher risk of CHD, but not stroke. These results provide further support for the current recommendations to limit UPF consumption for the prevention of CHD among patients with diabetes.

Sex differences in the intergenerational link between maternal and neonatal whole blood DNA methylation: a genome-wide analysis in 2 birth cohorts

Abstract: Abstract Background The mother–child inheritance of DNA methylation (DNAm) variations could contribute to the inheritance of disease susceptibility across generations. However, no study has investigated patterns of mother–child associations in DNAm at the genome-wide scale. It remains unknown whether there are sex differences in mother–child DNAm associations. Results Using genome-wide DNAm profiling data (721,331 DNAm sites, including 704,552 on autosomes and 16,779 on the X chromosome) of 396 mother–newborn pairs (54.5% male) from the Boston Birth Cohort, we found significant sex differences in mother–newborn correlations in genome-wide DNAm patterns (Spearman’s rho = 0.91–0.98; p = 4.0 × 10 –8 ), with female newborns having stronger correlations. Sex differences in correlations were attenuated but remained significant after excluding X-chromosomal DNAm sites (Spearman’s rho = 0.91–0.98; p = 0.035). Moreover, 89,267 DNAm sites (12.4% of all analyzed, including 88,051 [12.5% of analyzed] autosomal and 1,216 [7.2% of analyzed] X-chromosomal sites) showed significant mother–newborn associations in methylation levels, and the top autosomal DNAm sites had high heritability than the genome-wide background (e.g., the top 100 autosomal DNAm sites had a medium h 2 of 0.92). Additionally, significant interactions between newborn sex and methylation levels were observed for 11 X-chromosomal and 4 autosomal DNAm sites that were mapped to genes that have been associated with sex-specific disease/traits or early development (e.g., EFHC2 , NXY , ADCYAP1R1 , and BMP4 ). Finally, 18,769 DNAm sites (14,482 [77.2%] on the X chromosome) showed mother–newborn differences in methylation levels that were significantly associated with newborn sex, and the top autosomal DNAm sites had relatively small heritability (e.g., the top 100 autosomal DNAm sites had a medium h 2 of 0.23). These DNAm sites were mapped to 2,532 autosomal genes and 978 X-chromosomal genes with significant enrichment in pathways involved in neurodegenerative and psychological diseases, development, neurophysiological process, immune response, and sex-specific cancers. Replication analysis in the Isle of Wight birth cohort yielded consistent results. Conclusion In two independent birth cohorts, we demonstrated strong mother–newborn correlations in whole blood DNAm on both autosomes and ChrX, and such correlations vary substantially by sex. Future studies are needed to examine to what extent our findings contribute to developmental origins of pediatric and adult diseases with well-observed sex differences.

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

Abstract: The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevención con Dieta Mediterránea (PREDIMED) trial participants and incidence of AF. We conducted a nested case-control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention.Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16-1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF.Current Controlled Trials number, ISRCTN35739639.

Abstract MP56: Intake of Ultra-Processed Foods is Associated With an Increase in Risk for Type Two Diabetes: Results From Three U.S. Cohort Studies and a Meta-Analysis

Abstract: Introduction: There is limited evidence on the association between long-term consumption of ultra-processed foods (UPF) and the risk of type 2 diabetes (T2D), among the U.S population. The overall strength of this association has also not been established. Hypothesis: Higher intake of UPF is associated with a higher risk of T2D in U.S. adults. The pooled risk estimates from published literature reinforce the positive relationship between the UPF intakes and T2D. Methods: We first assessed this relationship among 71,871 women from the Nurses’ Health Study (NHS, 1984-2016), 87,918 women from NHSII (1991-2017), and 38,847 men from the Health Professionals Follow-up Study (HPFS, 1986-2016) who were all free of T2D at baseline. Diet was assessed using food frequency questionnaires, every 2-4 years. UPF were categorized according to the Nova classification. Information on incident cases of T2D was obtained through follow-up questionnaires every 2 years. The association between UPF intake and incident T2D was examined using Cox proportional hazards models. Second, after conducting a systematic review of prospective cohort studies, risk estimates from all included cohorts were pooled in a random-effects, dose-response, meta-analysis to assess nonlinearity of the association between total UPF intake and T2D risk. Finally, the strength of the meta-evidence was assessed using NutriGrade. Results: During 5,187,678 person-years of follow-up across the three cohorts, 19,503 T2D cases were documented. The pooled multivariable-adjusted hazard ratios (HRs) for T2D between the extreme quintiles of total UPF intake (% of grams/day), was 1.36 (95% confidence interval (CI): 1.29, 1.44; P trend <0.0001). This relationship was driven by intakes of ultra-processed animal-based products, ready-to-eat mixed dishes and artificially- and sugar-sweetened beverages. Ultra-processed cereals and ultra-processed dark breads and whole-grain breads were inversely associated with T2D risk. In the meta-analysis (7 risk estimates, 415,554 participants and 21,932 T2D cases), a significant positive dose-response association between total UPF intake and T2D was observed (P=0.90 for non-linearity): a 10% increase in total UPF intake (% grams from UPF/day) was associated with a 10% higher risk of T2D (95%CI: 8%, 12%; I 2 =23.1%; P heterogeneity =0.25). Per NutriGrade, the evidence supporting the positive relationship between total UPF intake and T2D was of high quality. Conclusions: High quality evidence shows that total UPF consumption is associated with higher risk of T2D, although not all individual foods classified as ultra-processed were associated with a higher risk in these U.S. cohorts.

Nuts and Cardiovascular Disease Outcomes: A Review of the Evidence and Future Directions

Abstract: Nuts are nutrient-rich foods that contain many bioactive compounds that are beneficial for cardiovascular health. Higher consumption of nuts has been associated with a reduced risk of several cardiovascular diseases (CVD) in prospective cohort studies, including a 19% and 25% lower risk of CVD incidence and mortality, respectively, and a 24% and 27% lower risk of coronary heart disease incidence and mortality, respectively. An 18% lower risk of stroke mortality, a 15% lower risk of atrial fibrillation, and a 19% lower risk of total mortality have also been observed. The role of nuts in stroke incidence, stroke subtypes, peripheral arterial disease and heart failure has been less consistent. This narrative review summarizes recommendations for nuts by clinical practice guidelines and governmental organizations, epidemiological evidence for nuts and CVD outcomes, nut-containing dietary patterns, potential mechanisms of nuts and CVD risk reduction, and future research directions, such as the use of biomarkers to help better assess nut intake. Although there are still some uncertainties around nuts and CVD prevention which require further research, as summarized in this review, there is a substantial amount of evidence that supports that consuming nuts will have a positive impact on primary and secondary prevention of CVD.

Abstract MP22: Plasma Metabolomic Profiles Associated With Mortality and Longevity in a Prospective Study of 13,401 Individuals

Abstract: Background: Recent advances in metabolomic studies have shown promise in elucidating the biological pathways underpinning aging processes and mortality in animal models, but data in humans are lacking. We aimed to evaluate the associations between metabolite profiles, all-cause and cause-specific mortality, and longevity. Methods: Within three prospective cohorts (Nurses’ Health Study [NHS], NHSII, and Health Professional’s Follow-up Study), we measured plasma metabolites from 11,523 participants (mean age 54 years, 86% female) using high-throughput liquid chromatography-mass spectrometry. Participants were free of cardiovascular disease and cancer at blood collection. Metabolome-wide association analyses were conducted for all-cause, cardiovascular, and cancer mortality using Cox proportional hazards regression and longevity (attaining 85 years of age) using logistic regression. Both pre-defined and data-driven metabolite groups were also evaluated. We further developed a multi-metabolite profile score for all-cause mortality using an elastic-net regularized Cox model and assessed its associations with mortality and longevity. Results for all-cause mortality were replicated among 1878 participants (mean age 67 years, 58% female) from the PREDIMED trial. Results: We documented 4252 deaths (including 864 cardiovascular deaths and 1070 cancer deaths) and 3048 achieving longevity over a median follow-up of 22.6 years in the NHS/NHSII/HPFS, and 126 deaths during a follow-up of 4.7 years in the PREDIMED. Higher levels of three nucleosides (N2,N2-dimethylguanosine, pseudouridine, and N4-acetylcytidine), 4-acetamidobutanoic acid, triacylglycerols with ≤56 carbons and ≤3 double bonds, and several other lipids were associated with increased risk of all-cause mortality and corresponding decreased likelihood of longevity; whereas L-serine, L-glutamine, and TAGs with >56 carbons or >3 double bonds were associated with lower mortality risk and higher odds of achieving longevity. A multi-metabolite profile score comprising 73 metabolites was positively associated with all-cause (HR per 1-SD increment=1.25 [95% CI: 1.21, 1.30] in NHS/NHSII/HPFS and 1.47 [95% CI: 1.22, 1.78] in PREDIMED), cardiovascular (HR=1.34 [95% CI:1.24, 1.45]), and cancer mortality (HR=1.15 [95% CI:1.08, 1.24]) and inversely associated with longevity (OR=0.79 [95% CI: 0.74, 0.86]). Conclusions: We identified multiple metabolites associated with mortality and longevity. Our findings provide insights into the biological pathways that lead to death and open up new avenues to incorporate these metabolomic markers in clinical and research settings.

Abstract MP66: The Interplay Between Diet, Circulating Indolepropionate Concentrations, and Cardiometabolic Health in US Populations

Abstract: Background: Indolepropionate (IPA), a tryptophan metabolite of human gut microbiota origin, is associated with lower risk of type 2 diabetes (T2D) in humans. The complex interplay among tryptophan intake, the gut microbiome, prebiotics, circulating IPA concentrations, and T2D risk has not been investigated. Objectives: We aimed to identify IPA-producing gut microbiota species and investigate potential diet-microbiota interaction on circulating IPA concentrations. Methods: We included 287 men from the Men’s Lifestyle Validation Study, a sub-study of the Health Professionals Follow-Up Study (HPFS), who provided up to two pairs of fecal samples and two blood samples approximately six months apart. Dietary intake was assessed using 7-day diet records. We identified microbial taxonomic features associated with plasma IPA concentrations using generalized linear regression and calculated a rank-based species score to reflect IPA-producing potential. Associations between plasma concentrations of tryptophan metabolites and T2D risk were examined in 13,032 participants from Nurses’ Health Study (NHS), NHSII, and HPFS. Results: Plasma IPA concentrations were associated with overall gut microbial profiles (permutational analysis of variance test, p=0.001). We identified 17 microbial species, such as Eubacterium eligens, Butyrivibrio crossotus , and Faecalibacterium prausnitzii , whose abundance was significantly associated with increased plasma IPA concentrations (false discovery rate < 0.05). A significant association between higher tryptophan intake and higher IPA concentrations was only observed among men who had higher fiber intake and a higher microbial species score consisting of the 17 species (p-interaction < 0.01). Similar modulation was also observed for major tryptophan food contributors including vegetables (p-interaction < 0.01), red/processed meat (p-interaction = 0.02), egg (p-interaction 0.01), dairy (p-interaction = 0.01), and whole grain (p-interaction < 0.01). Moreover, interactions persisted for all fiber subtypes (soluble/insoluble fiber and pectin). We documented 1,744 incident T2D cases during 218,603 person-years of follow-up. Plasma concentrations of tryptophan and three kynurenine-pathway metabolites (kynurenine, xanthurenate, and quinolinate) were positively associated with T2D risk while an inverse association was found for IPA. Conclusions: Specific microbial species and dietary fiber jointly modulate the associations between tryptophan intake and circulating IPA concentrations. In a subsequent analysis, IPA levels were predictive of lower T2D risk. Our findings suggest that the health effects of dietary tryptophan may depend on both gut microbiome composition and prebiotic consumption.

Urinary metabolomics of phenolic compounds reveals biomarkers of type-2 diabetes within the PREDIMED trial.

Abstract: Phenolic compounds have been associated with protective effects against type-2 diabetes (T2D). We used a metabolomics approach to determine urinary phenolic metabolites associated with T2D and fasting plasma glucose.This case-control study within the PREDIMED trial included 200 participants at high cardiovascular risk, 102 of whom were diagnosed with T2D. A panel of urinary phenolic compounds were analysed using a novel method based on liquid chromatography coupled to mass spectrometry. Multivariate statistics and adjusted logistic regressions were applied to determine the most discriminant compounds and their association with T2D. The relationship between the discriminant phenolic compounds and plasma glucose was assessed using multivariable linear regressions.A total of 41 phenolic compounds were modeled in the orthogonal projection to latent structures discriminant analysis, and after applying adjusted logistic regressions two were selected as discriminant: dihydrocaffeic acid (OR = 0.22 (CI 95 %: 0.09; 0.52) per 1-SD, p-value = 0.021) and genistein diglucuronide (OR = 0.72 (CI 95%: 0.59; 0.88) per 1-SD, p-value = 0.021). Both metabolites were associated with a lower risk of suffering from T2D, but only dihydrocaffeic acid was inversely associated with plasma glucose (β = -17.12 (95 % CI: -29.92; -4.32) mg/dL per 1-SD, p-value = 0.009).A novel method using a metabolomics approach was developed to analyse a panel of urinary phenolic compounds for potential associations with T2D, and two metabolites, dihydrocaffeic acid and genistein diglucuronide, were found to be associated with a lower risk of this condition.