Showing papers by "Frank B. Hu published in 2022"

The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases

Abstract: Sugar-sweetened beverages (SSBs) are a major source of added sugars in the diet. A robust body of evidence has linked habitual intake of SSBs with weight gain and a higher risk (compared with infrequent SSB consumption) of type 2 diabetes mellitus, cardiovascular diseases and some cancers, which makes these beverages a clear target for policy and regulatory actions. This Review provides an update on the evidence linking SSBs to obesity, cardiometabolic outcomes and related cancers, as well as methods to grade the strength of nutritional research. We discuss potential biological mechanisms by which constituent sugars can contribute to these outcomes. We also consider global trends in intake, alternative beverages (including artificially-sweetened beverages) and policy strategies targeting SSBs that have been implemented in different settings. Strong evidence from cohort studies on clinical outcomes and clinical trials assessing cardiometabolic risk factors supports an aetiological role of SSBs in relation to weight gain and cardiometabolic diseases. Many populations show high levels of SSB consumption and in low-income and middle-income countries, increased consumption patterns are associated with urbanization and economic growth. As such, more intensified policy efforts are needed to reduce intake of SSBs and the global burden of obesity and chronic diseases. Evidence from cohort studies and clinical trials supports an aetiological role of sugar-sweetened beverage (SSB) intake in the development of obesity and related chronic diseases. This Review provides an up-to-date view, considering the evidence, potential mechanisms and policy actions to reduce the global intake of SSBs.

Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies

Abstract: BACKGROUND Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted. PURPOSE To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes. DATA SOURCES We searched PubMed and Embase until 6 March 2021. STUDY SELECTION We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes. DATA EXTRACTION Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies. DATA SYNTHESIS A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate–corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07–2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69–0.90). LIMITATIONS Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites. CONCLUSIONS Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop

Abstract: Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

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

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

Stability and reproducibility of proteomic profiles in epidemiological studies: comparing the Olink and SOMAscan platforms

Abstract: Limited data exist on the performance of high‐throughput proteomics profiling in epidemiological settings, including the impact of specimen collection and within‐person variability over time. Thus, the Olink (972 proteins) and SOMAscan7Kv4.1 (7322 proteoforms of 6596 proteins) assays were utilized to measure protein concentrations in archived plasma samples from the Nurses’ Health Studies and Health Professionals Follow‐Up Study. Spearman's correlation coefficients (r) and intraclass correlation coefficients (ICCs) were used to assess agreement between (1) 42 triplicate samples processed immediately, 24‐h or 48‐h after blood collection from 14 participants; and (2) 80 plasma samples from 40 participants collected 1‐year apart. When comparing samples processed immediately, 24‐h, and 48‐h later, 55% of assays had an ICC/r ≥ 0.75 and 87% had an ICC/r ≥ 0.40 in Olink compared to 44% with an ICC/r ≥ 0.75 and 72% with an ICC/r ≥ 0.40 in SOMAscan7K. For both platforms, >90% of the assays were stable (ICC/r ≥ 0.40) in samples collected 1‐year apart. Among 817 proteins measured with both platforms, Spearman's correlations were high (r > 0.75) for 14.7% and poor (r < 0.40) for 44.8% of proteins. High‐throughput proteomics profiling demonstrated reproducibility in archived plasma samples and stability after delayed processing in epidemiological studies, yet correlations between proteins measured with the Olink and SOMAscan7K platforms were highly variable.

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial

Abstract: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT).In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues.Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models).A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.ClinicalTrials.gov , NCT03020186.

Plasma metabolite profiles related to plant-based diets and the risk of type 2 diabetes

Abstract: Plant-based diets, especially when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes. However, whether plasma metabolite profiles related to plant-based diets reflect this association was unknown. The aim of this study was to identify the plasma metabolite profiles related to plant-based diets, and to evaluate the associations between the identified metabolite profiles and the risk of type 2 diabetes.Within three prospective cohorts (Nurses' Health Study, Nurses' Health Study II and Health Professionals Follow-up Study), we measured plasma metabolites from 10,684 participants using high-throughput LC MS. Adherence to plant-based diets was assessed by three indices derived from the food frequency questionnaire: an overall Plant-based Diet Index (PDI), a Healthy Plant-based Diet Index (hPDI), and an Unhealthy Plant-based Diet Index (uPDI). Multi-metabolite profiles related to plant-based diet were identified using elastic net regression with a training/testing approach. The prospective associations between metabolite profiles and incident type 2 diabetes were evaluated using multivariable Cox proportional hazards regression. Metabolites potentially mediating the association between plant-based diets and type 2 diabetes risk were further identified.We identified multi-metabolite profiles comprising 55 metabolites for PDI, 93 metabolites for hPDI and 75 metabolites for uPDI. Metabolite profile scores based on the identified metabolite profiles were correlated with the corresponding diet index (Pearson r = 0.33-0.35 for PDI, 0.41-0.45 for hPDI, and 0.37-0.38 for uPDI, all p<0.001). Metabolite profile scores of PDI (HR per 1 SD higher = 0.81 [95% CI 0.75, 0.88]) and hPDI (HR per 1 SD higher = 0.77 [95% CI 0.71, 0.84]) showed an inverse association with incident type 2 diabetes, whereas the metabolite profile score for uPDI was not associated with the risk. Mutual adjustment for metabolites selected in the metabolite profiles, including trigonelline, hippurate, isoleucine and a subset of triacylglycerols, attenuated the associations of diet indices PDI and hPDI with lower type 2 diabetes risk. The explainable proportion of PDI/hPDI-related diabetes risk by these metabolites ranged between 8.5% and 37.2% (all p<0.05).Plasma metabolite profiles related to plant-based diets, especially a healthy plant-based diet, were associated with a lower risk of type 2 diabetes among a generally healthy population. Our findings support the beneficial role of healthy plant-based diets in diabetes prevention and provide new insights for future investigation.

Dietary lignans, plasma enterolactone levels, and metabolic risk in men: exploring the role of the gut microbiome

Abstract: Abstract Background The conversion of plant lignans to bioactive enterolignans in the gastrointestinal tract is mediated through microbial processing. The goal of this study was to examine the relationships between lignan intake, plasma enterolactone concentrations, gut microbiome composition, and metabolic risk in free-living male adults. Results In 303 men participating in the Men’s Lifestyle Validation Study (MLVS), lignan intake was assessed using two sets of 7-day diet records, and gut microbiome was profiled through shotgun sequencing of up to 2 pairs of fecal samples ( n = 911). A score was calculated to summarize the abundance of bacteria species that were significantly associated with plasma enterolactone levels. Of the 138 filtered species, plasma enterolactone levels were significantly associated with the relative abundances of 18 species at FDR < 0.05 level. Per SD increment of lignan intake was associated with 20.7 nM (SEM: 2.3 nM) higher enterolactone concentrations among participants with a higher species score, whereas the corresponding estimate was 4.0 nM (SEM: 1.7 nM) among participants with a lower species score ( P for interaction < 0.001). A total of 12 plasma metabolites were also significantly associated with these enterolactone-predicting species. Of the association between lignan intake and metabolic risk, 19.8% (95%CI: 7.3%-43.6%) was explained by the species score alone, 54.5% (95%CI: 21.8%-83.7%) by both species score and enterolactone levels, and 79.8% (95%CI: 17.7%-98.6%) by further considering the 12 plasma metabolites. Conclusion We identified multiple gut bacteria species that were enriched or depleted at higher plasma levels of enterolactone in men. These species jointly modified the associations of lignan intake with plasma enterolactone levels and explained the majority of association between lignan intake and metabolic risk along with enterolactone levels and certain plasma metabolites.

Protein intake and risk of frailty among older women in the Nurses' Health Study

Abstract: There is evidence that an overall healthy diet is associated with lower risk of frailty. However, the effect of diet composition, specifically the role of protein intake on frailty, is mostly unclear. The aim of this study was to evaluate the intake of protein, including total, plant, animal, and dairy protein, in relation to frailty incidence in a large cohort of older women.

Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study

Abstract: Abstract Objectives To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, US. Participants 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. Main outcome measure Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifthsof the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). Results Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (Ptrend<0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (Ptrend<0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. Conclusions Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.

Association between ultra-processed food consumption and gut microbiota in senior subjects with overweight/obesity and metabolic syndrome

Abstract: The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects (n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55–75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and <40 kg/m2) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 ± 5.0 % kcal/day) presented lower adherence to MedDiet (p < 0.001) and higher total energy intake (p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive association between specific taxa and tertiles (T) of UPF consumption: Alloprevotella (p = 0.041 vs. T2; p = 0.065 vs. T3), Negativibacillus (p = 0.096 vs. T3), Prevotella (p = 0.116 vs. T3), and Sutterella (p = 0.116 vs. T2). UPF consumption was positively associated with lower adherence to MedDiet and higher total energy intake in senior subjects with overweight obesity and metabolic syndrome. In addition, positive association with specific fecal microbiota taxa related to inflammatory gastro-intestinal diseases and low consumption of fruits and vegetables, was observed.

Polygenic scores, diet quality, and type 2 diabetes risk: An observational study among 35,759 adults from 3 US cohorts

Abstract: Background Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findings We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. Conclusions These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.

Intrapersonal Stability of Plasma Metabolomic Profiles over 10 Years among Women

Abstract: In epidemiological studies, samples are often collected long before disease onset or outcome assessment. Understanding the long-term stability of biomarkers measured in these samples is crucial. We estimated within-person stability over 10 years of metabolites and metabolite features (n = 5938) in the Nurses’ Health Study (NHS): the primary dataset included 1880 women with 1184 repeated samples donated 10 years apart while the secondary dataset included 1456 women with 488 repeated samples donated 10 years apart. We quantified plasma metabolomics using two liquid chromatography mass spectrometry platforms (lipids and polar metabolites) at the Broad Institute (Cambridge, MA, USA). Intra-class correlations (ICC) were used to estimate long-term (10 years) within-person stability of metabolites and were calculated as the proportion of the total variability (within-person + between-person) attributable to between-person variability. Within-person variability was estimated among participants who donated two blood samples approximately 10 years apart while between-person variability was estimated among all participants. In the primary dataset, the median ICC was 0.43 (1st quartile (Q1): 0.36; 3rd quartile (Q3): 0.50) among known metabolites and 0.41 (Q1: 0.34; Q3: 0.48) among unknown metabolite features. The three most stable metabolites were N6,N6-dimethyllysine (ICC = 0.82), dimethylguanidino valerate (ICC = 0.72), and N-acetylornithine (ICC = 0.72). The three least stable metabolites were palmitoylethanolamide (ICC = 0.05), ectoine (ICC = 0.09), and trimethylamine-N-oxide (ICC = 0.16). Results in the secondary dataset were similar (Spearman correlation = 0.87) to corresponding results in the primary dataset. Within-person stability over 10 years is reasonable for lipid, lipid-related, and polar metabolites, and varies by metabolite class. Additional studies are required to estimate within-person stability over 10 years of other metabolites groups.

Dietary lignans, plasma enterolactone levels, and metabolic risk in men: exploring the role of the gut microbiome

Abstract: Abstract Background The conversion of plant lignans to bioactive enterolignans in the gastrointestinal tract is mediated through microbial processing. The goal of this study was to examine the relationships between lignan intake, plasma enterolactone concentrations, gut microbiome composition, and metabolic risk in free-living male adults. Results In 303 men participating in the Men’s Lifestyle Validation Study (MLVS), lignan intake was assessed using two sets of 7-day diet records, and gut microbiome was profiled through shotgun sequencing of up to 2 pairs of fecal samples ( n = 911). A score was calculated to summarize the abundance of bacteria species that were significantly associated with plasma enterolactone levels. Of the 138 filtered species, plasma enterolactone levels were significantly associated with the relative abundances of 18 species at FDR < 0.05 level. Per SD increment of lignan intake was associated with 20.7 nM (SEM: 2.3 nM) higher enterolactone concentrations among participants with a higher species score, whereas the corresponding estimate was 4.0 nM (SEM: 1.7 nM) among participants with a lower species score ( P for interaction < 0.001). A total of 12 plasma metabolites were also significantly associated with these enterolactone-predicting species. Of the association between lignan intake and metabolic risk, 19.8% (95%CI: 7.3%-43.6%) was explained by the species score alone, 54.5% (95%CI: 21.8%-83.7%) by both species score and enterolactone levels, and 79.8% (95%CI: 17.7%-98.6%) by further considering the 12 plasma metabolites. Conclusion We identified multiple gut bacteria species that were enriched or depleted at higher plasma levels of enterolactone in men. These species jointly modified the associations of lignan intake with plasma enterolactone levels and explained the majority of association between lignan intake and metabolic risk along with enterolactone levels and certain plasma metabolites.

Avocado Consumption and Risk of Cardiovascular Disease in US Adults

Abstract: Background Epidemiologic studies on the relationship between avocado intake and long‐term cardiovascular disease (CVD) risk are lacking. Methods and Results This study included 68 786 women from the NHS (Nurses’ Health Study) and 41 701 men from the HPFS (Health Professionals Follow‐up Study; 1986–2016) who were free of cancer, coronary heart disease, and stroke at baseline. Diet was assessed using validated food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios and 95% CIs. A total of 14 274 incident cases of CVD (9185 coronary heart disease events and 5290 strokes) were documented over 30 years of follow‐up. After adjusting for lifestyle and other dietary factors, compared with nonconsumers, those with analysis‐specific higher avocado intake (≥2 servings/week) had a 16% lower risk of CVD (pooled hazard ratio, 0.84; 95% CI, 0.75–0.95) and a 21% lower risk of coronary heart disease (pooled hazard ratio, 0.79; 95% CI, 0.68–0.91). No significant associations were observed for stroke. Per each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80 (95% CI, 0.71–0.91). Replacing half a serving/day of margarine, butter, egg, yogurt, cheese, or processed meats with the equivalent amount of avocado was associated with a 16% to 22% lower risk of CVD. Conclusions Higher avocado intake was associated with lower risk of CVD and coronary heart disease in 2 large prospective cohorts of US men and women. The replacement of certain fat‐containing foods with avocado could lead to lower risk of CVD.

Healthful eating patterns, serum metabolite profile and risk of diabetes in a population-based prospective study of US Hispanics/Latinos

Abstract: We aimed to evaluate associations of multiple recommended dietary patterns (i.e. the alternate Mediterranean diet [aMED], the Healthy Eating Index [HEI]-2015 and the healthful Plant-based Diet Index [hPDI]) with serum metabolite profile, and to examine dietary-pattern-associated metabolites in relation to incident diabetes.We included 2842 adult participants free from diabetes, CVD and cancer during baseline recruitment of the Hispanic Community Health Study/Study of Latinos. Metabolomics profiling of fasting serum was performed using an untargeted approach. Dietary pattern scores were derived using information collected by two 24 h dietary recalls. Dietary-pattern-associated metabolites were identified using multivariable survey linear regressions and their associations with incident diabetes were assessed using multivariable survey Poisson regressions with adjustment for traditional risk factors.We identified eight metabolites (mannose, γ/β-tocopherol, N1-methylinosine, pyrraline and four amino acids) that were inversely associated with all dietary scores. These metabolites were detrimentally associated with various cardiometabolic risk traits, especially insulin resistance. A score comprised of these metabolites was associated with elevated risk of diabetes (RRper SD 1.54 [95% CI 1.29, 1.83]), and this detrimental association appeared to be attenuated or eliminated by having a higher score for aMED (pinteraction = 0.0001), HEI-2015 (pinteraction = 0.020) or hPDI (pinteraction = 0.023). For example, RR (95% CI) of diabetes for each SD increment in the metabolite score was 1.99 (1.44, 2.37), 1.67 (1.17, 2.38) and 1.08 (0.86, 1.34) across the lowest to the highest tertile of aMED score, respectively.Various recommended dietary patterns were inversely related to a group of metabolites that were associated with elevated risk of diabetes. Adhering to a healthful eating pattern may attenuate or eliminate the detrimental association between metabolically unhealthy serum metabolites and risk of diabetes.

Association between the quality of plant‐based diets and risk of frailty

Abstract: The Mediterranean diet and other dietary patterns rich in fruits and vegetables have been linked to lower risk of frailty in older adults. However, not all plant‐based diets are necessarily healthful, and no previous study has evaluated the role of the quality of plant‐based dietary patterns in frailty risk. Our aim was to assess the association between plant‐based diet quality and risk of frailty.

White rice, brown rice and the risk of type 2 diabetes: a systematic review and meta-analysis

Abstract: Objective Intake of white rice has been associated with elevated risk for type 2 diabetes (T2D), while studies on brown rice are conflicting. To inform dietary guidance, we synthesised the evidence on white rice and brown rice with T2D risk. Design Systematic review and meta-analysis. Data sources PubMed, EMBASE and Cochrane databases were searched through November 2021. Eligibility criteria Prospective cohort studies of white and brown rice intake on T2D risk (≥1 year), and randomised controlled trials (RCTs) comparing brown rice with white rice on cardiometabolic risk factors (≥2 weeks). Data extraction and synthesis Data were extracted by the primary reviewer and two additional reviewers. Meta-analyses were conducted using random-effects models and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the Newcastle Ottawa Scale for prospective cohort studies and the Cochrane Risk of Bias Tool for RCTs. Strength of the meta-evidence was assessed using NutriGrade. Results Nineteen articles were included: 8 cohort studies providing 18 estimates (white rice: 15 estimates, 25 956 cases, n=5 77 426; brown rice: 3 estimates, 10 507 cases, n=1 97 228) and 11 RCTs (n=1034). In cohort studies, white rice was associated with higher risk of T2D (pooled RR, 1.16; 95% CI: 1.02 to 1.32) comparing extreme categories. At intakes above ~300 g/day, a dose–response was observed (each 158 g/day serving was associated with 13% (11%–15%) higher risk of T2D). Intake of brown rice was associated with lower risk of T2D (pooled RR, 0.89; 95% CI: 0.81 to 0.97) comparing extreme categories. Each 50 g/day serving of brown rice was associated with 13% (6%–20%) lower risk of T2D. Cohort studies were considered to be of good or fair quality. RCTs showed an increase in high-density lipoprotein-cholesterol (0.06 mmol/L; 0.00 to 0.11 mmol/L) in the brown compared with white rice group. No other significant differences in risk factors were observed. The majority of RCTs were found to have some concern for risk of bias. Overall strength of the meta-evidence was moderate for cohort studies and moderate and low for RCTs. Conclusion Intake of white rice was associated with higher risk of T2D, while intake of brown rice was associated with lower risk. Findings from substitution trials on cardiometabolic risk factors were inconsistent. PROSPERO registration number CRD42020158466.

Effects of a Low-Carbohydrate Dietary Intervention on Hemoglobin A1c

Abstract: Key Points Question What is the effect of a dietary intervention promoting a low-carbohydrate diet compared with usual diet on 6-month change in hemoglobin A1c among adults with untreated hemoglobin A1c of 6.0% to 6.9%? Findings In this randomized clinical trial that included 150 adults, the low-carbohydrate diet intervention significantly reduced hemoglobin A1c by 0.23% compared with usual diet over 6 months. Meaning These findings suggest that a low-carbohydrate diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed.

Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program

Abstract: Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.

Association between a lifestyle-based healthy heart score and risk of frailty in older women: a cohort study.

Abstract: BACKGROUND Evidence on the comprehensive role of lifestyle in frailty risk is scarce. To assess the association between a lifestyle-based Healthy Heart Score (HHS), which estimates the 20-year risk of cardiovascular disease (CVD), and risk of frailty among older women. METHODS Prospective cohort study in 121,700 nurses from the USA participating at the Nurses' Health Study. This study included 68,416 women aged ≥60 year with a follow-up from 1990 to 2014. The HHS was computed using the gender-specific beta-coefficients of the nine lifestyle factors, including current smoking, high body mass index, low physical activity, lack of moderate alcohol intake and unhealthy diet. Frailty incidence was assessed every 4 years from 1992 to 2014 as having ≥3 of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses and weight loss ≥5%. RESULTS During 22 years of follow-up, 11,041 total incident cases of frailty were ascertained. Compared to women in the lowest quintile of the HHS (lowest estimated CVD risk), the multivariable-adjusted hazard ratio of frailty across quintiles was: Q2:1.67 (95% confidence interval 1.53, 1.82); Q3: 2.34 (2.15, 2.53); Q4: 3.54 (3.28, 3.83) and Q5: 5.92 (5.48, 6.38); P-trend > 0.001. Results were consistent for each frailty criterion, among participants with 0 frailty criteria at baseline, when using only baseline exposure or in 6-year-, 10-year- and 14-year-exposure lagged analyses, and after excluding participants with diabetes and CVD at baseline. CONCLUSIONS The HHS, based on a set of modifiable-lifestyle factors, is strongly associated with risk of frailty in older women.

Abstract 020: Healthy Dietary Patterns And Risk Of Cardiovascular Disease In Us Hispanics/latinos: The Hispanic Community Health Study/study Of Latinos (HCHS/SOL)

Abstract: Introduction: Multiple healthy eating patterns have been recommended by the Dietary Guidelines for Americans (2015-2020) for the prevention of cardiovascular disease (CVD). However, adherence to these dietary patterns and its relationship with risk of CVD remains unclear among US Hispanic/Latinos. Hypothesis: We aimed to evaluate three healthy eating patterns measured by three dietary quality indices (the Alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful Plant-based Diet Index (hPDI)), and assessed the hypothesis that higher adherence to healthy eating patterns is associated with lower risk of CVD in US Hispanic/Latinos. Methods: We included 10,766 adult participants representing six Hispanic/Latino backgrounds (Mexican, Puerto Rican, Cuban, Dominican, Central American and South American), free of CVD or cancer at baseline, from the Hispanic Community Health Study/Study of Latinos. Dietary pattern scores were derived using information collected by two 24-hour dietary recalls at baseline (2008-11). The primary outcome was major incident CVD (n=248), comprised of coronary heart disease and stroke, during an average 6-year follow-up period. Relative risks for CVD were estimated using survey Poisson regression after adjustment for demographic, socioeconomic, and behavioral variables and sampling weights. Results: Mean scores of all three dietary quality indices were significantly different across six Hispanic/Latino background groups (all P <0.001), with the highest (healthier) in Mexicans and lowest in Puerto Ricans. Compared to Hispanics/Latinos who were born outside the mainland US, US-born Hispanics/Latinos had significantly lower dietary quality scores (all P <0.001), especially in Mexican, Dominican, and Central American background groups. The differences in dietary scores between the non-US-born and US-born Hispanics/Latinos were primarily driven by intakes of healthy plant-based foods (e.g., whole grains, fruits, vegetables, legumes and nuts). We found significant inverse associations across tertiles of the three dietary indices with risk of CVD. After multivariable adjustment, the relative risk of CVD was 0.54 (95% CI 0.37-0.81; P -trend=0.002) for aMED, 0.64 (95% CI 0.39-1.05; P -trend=0.033) for HEI-2015, and 0.56 (95% CI, 0.35-0.88; P -trend=0.009) for hPDI when comparing highest to lowest tertiles in the overall sample. The associations between dietary quality scores and risk of CVD were not different across Hispanic/Latino backgrounds (all P for interaction ≥0.24) or not by US-born status (all P for interaction ≥0.25). Conclusions: Adherence to healthy eating patterns reflected by three diet quality indices varied by Hispanic/Latino background and immigrant generation, and higher compliance to healthy eating patterns was associated with lower risk of CVD risk in the US Hispanic/Latino population.