Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes.

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio, Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio, with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.

Nutritional Blood Concentration Biomarkers in the Hispanic Community Health Study/Study of Latinos: Measurement Characteristics and Power.

Measurement error is a major issue in self-reported diet that can distort diet-disease relationships. Use of blood concentration biomarkers has the potential to mitigate the subjective bias inherent in self-reporting. As part of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline visit (2008-2011), self-reported information on diet was collected from all participants (n = 16,415). The HCHS/SOL also included annual telephone follow-up, as well as a second (2014-2017) and third (2020-2023) clinic visit. Blood concentration biomarkers for carotenoids, tocopherols, retinol, vitamin B12, and folate were measured in a subset of participants (n = 476) as part of the Study of Latinos: Nutrition and Physical Activity Assessment Study (SOLNAS) (2010-2012). We examined the relationships among biomarker levels, self-reported intake, Hispanic/Latino background (Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American), and other participant characteristics in this diverse cohort. We built regression calibration-based prediction equations for 10 nutritional biomarkers and used a simulation to study the power of detecting a diet-disease association in a multivariable Cox model using a predicted concentration level. Good statistical power was observed for some nutrients with high prediction model R2 values, but further research is needed to understand how best to realize the potential of these dietary biomarkers. This study provides a comprehensive examination of several nutritional biomarkers within the HCHS/SOL, characterizing their associations with subject characteristics and the influence of the measurement characteristics on the power to detect associations with health outcomes.

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study.

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: This study aimed to identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.

Associations of Biomarker-Calibrated Healthy Eating Index-2010 Scores with Chronic Disease Risk and Their Dependency on Energy Intake and Body Mass Index in Postmenopausal Women.

BACKGROUND: Prior studies examined associations between the Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction. OBJECTIVE: Our objective was to test associations between biomarker calibration of the food-frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) among Women's Health Initiative (WHI) participants. METHODS: Data were derived from WHI postmenopausal women (n = 100,374) aged 50-79 y at enrollment (1993-1998) at 40 US clinical centers, linked to nutritional biomarker substudies and outcomes over subsequent decades of follow-up. Baseline or year 1 FFQ-derived HEI-2010 scores were calibrated with nutritional biomarkers and participant characteristics (e.g., BMI) for systematic measurement error correction. Calibrated data were then used in HR models examining associations with incidence of CVD (total, subtypes, mortality), cancer (total, subtypes, mortality), and T2D in WHI participants with approximately 2 decades of follow-up. Models were multivariable-adjusted with further adjustment for BMI and doubly labeled water (DLW)-calibrated energy. RESULTS: Multivariable-adjusted HRs modeled a 20% increment in HEI-2010 score in relation to outcomes. HRs were modest using uncalibrated HEI-2010 scores (HRs = 0.91-1.09). Using biomarker-calibrated HEI-2010, 20% increments in scores yielded multivariable-adjusted HRs (95% CIs) of 0.75 (0.60, 0.93) for coronary heart disease; 0.75 (0.61, 0.91) for myocardial infarction; 0.96 (0.92, 1.01) for stroke; 0.88 (0.75, 1.02) for CVD mortality; 0.81 (0.70, 0.94) for colorectal cancer; 0.81 (0.74, 0.88) for breast cancer; 0.79 (0.73, 0.87) for cancer mortality; and 0.45 (0.36-0.55) for T2D. Except for cancer mortality and T2D incidence, results became null when adjusted for DLW-calibrated energy intake and BMI. CONCLUSIONS: Biomarker calibration of FFQ-derived HEI-2010 was associated with lower CVD and cancer incidence and mortality and lower T2D incidence in postmenopausal women. Attenuation after adjustment with BMI and DLW-calibrated energy suggests that energy intake and/or obesity are strong drivers of diet-related chronic disease risk in postmenopausal women. The Women's Health Initiative is registered at clinicaltrials.gov at NCT00000611.

Metabolomics-Based Biomarker for Dietary Fat and Associations with Chronic Disease Risk in Postmenopausal Women.

BACKGROUND: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern. OBJECTIVES: We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts. Corresponding studies for specific fatty acids will follow separately. METHODS: Prospective disease association results are presented using WHI cohorts of postmenopausal women, aged 50-79 y when enrolled at 40 United States clinical centers. Biomarker equations were developed using an embedded human feeding study (n = 153). Calibration equations were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with cancer, cardiovascular diseases, and diabetes incidence in WHI cohorts (n = 81,954) over an approximate 20-y follow-up period. RESULTS: A biomarker for fat density was developed by subtracting protein, carbohydrate, and alcohol densities from one. A calibration equation was developed for fat density. Hazard ratios (95% confidence intervals) for 20% higher fat density were 1.16 (1.06, 1.27) for breast cancer, 1.13 (1.02, 1.26) for CHD, and 1.19 (1.13, 1.26) for diabetes, in substantial agreement with findings from the DM trial. With control for additional dietary variables, especially fiber, fat density was no longer associated with CHD, with hazard ratio (95% confidence interval) of 1.00 (0.88, 1.13), whereas that for breast cancer was 1.11 (1.00, 1.24). CONCLUSIONS: WHI observational data support prior DM trial findings of low-fat dietary pattern benefits in this population of postmenopausal United States women. TRIAL REGISTRATION NUMBER: This study is registered with clinicaltrials.gov identifier: NCT00000611.

Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women.

BACKGROUND: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data. OBJECTIVES: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women's Health Initiative (WHI) cohorts. METHODS: Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153). Calibration equations were based on biomarker values in a WHI nutritional biomarker study (n = 436). Calibrated intakes were assessed in relation to disease incidence in larger WHI cohorts (n = 81,894). Participants were postmenopausal women, aged 50-79 when enrolled at 40 United States Clinical Centers (1993-1998), with a follow-up period of ∼20 y. RESULTS: Biomarker equations meeting criteria were developed for SFA, MUFA, and PUFA densities. That for SFA density depended somewhat weakly on metabolite profiles. On the basis of our metabolomics platforms, biomarkers were insensitive to trans fatty acid intake. Calibration equations meeting criteria were developed for SFA and PUFA density, but not for MUFA density. With or without biomarker calibration, SFA density was associated positively with risk of CVD, cancer, and T2D, but with small hazard ratios, and CVD associations were not statistically significant after controlling for other dietary variables, including trans fatty acid and fiber intake. Following this same control, PUFA density was not significantly associated with CVD risk, but there were positive associations for some cancers and T2D, with or without biomarker calibration. CONCLUSIONS: Higher SFA and PUFA diets were associated with null or somewhat higher risk for clinical outcomes considered in this population of postmenopausal United States women. Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components. This study is registered with clinicaltrials.gov identifier: NCT00000611.

Characterizing longitudinal change in accelerometry-based moderate-to-vigorous physical activity in the Hispanic Community Health Study/Study of Latinos and the Framingham Heart Study.

BACKGROUND: Physical activity promotes health and is particularly important during middle and older age for decreasing morbidity and mortality. We assessed the correlates of changes over time in moderate-to-vigorous physical activity (MVPA) in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL: mean [SD] age 49.2 y [11.5]) and compared them to a cohort of primarily White adults from the Framingham Heart Study (FHS: mean [SD] 46.9 y [9.2]). METHODS: Between 2008 and 2019, we assessed accelerometry-based MVPA at two time points with an average follow-up of: 7.6 y, SD 1.3 for HCHS/SOL, and 7.8 y, SD 0.7 for FHS. We used multinomial logistic regression to relate socio-demographic and health behaviors with changes in compliance with 2018 US recommendations for MVPA from time 1 to time 2 (remained active or inactive; became active or inactive) across the two cohorts. RESULTS: In HCHS/SOL mean MVPA was 22.6 (SD, 23.8) minutes at time 1 and dropped to 16.7 (19.0) minutes at time 2. In FHS Mean MVPA was 21.7 min (SD, 17.7) at time 1 and dropped to 21.3 min (SD, 19.2) at time 2. Across both cohorts, odds of meeting MVPA guidelines over time were about 6% lower in individuals who had lower quality diets vs. higher, about half in older vs. younger adults, about three times lower in women vs. men, and 9% lower in individuals who had a higher vs. lower BMI at baseline. Cohorts differed in how age, gender, income, education, depressive symptoms, marital status and perception of general health and pain associated with changes in physical activity. High income older Hispanics/Latino adults were more likely to become inactive at the follow-up visit as were HCHS/SOL women who were retired and FHS participants who had lower levels of education and income. Higher depressive symptomology was associated with becoming active only in HCHS/SOL women. Being male and married was associated with becoming inactive in both cohorts. Higher perception of general health and lower perception of pain were associated with remaining active only in FHS adults. CONCLUSIONS: These findings highlight potentially high-risk groups for targeted MVPA intervention.

Association of Dietary Potassium Intake With Abdominal Aortic Calcification and Pulse Pressure in US Adults.

OBJECTIVES: Arterial calcification contributes to cardiovascular mortality. Based on a recent animal study, we hypothesized that higher dietary potassium intake was associated with less abdominal aortic calcification (AAC) and lower arterial stiffness among adults in the United States. METHODS: Cross-sectional analyses were performed on participants over 40 years old from the National Health and Nutrition Examination Survey 2013-2014. Dietary potassium intake was categorized into quartiles (Q1: <1911, Q2: 1911-2461, Q3: 2462-3119, and Q4: >3119 mg/d). Primary outcome AAC was quantified using the Kauppila scoring system. AAC scores were categorized into no AAC (AAC = 0, reference group), mild/moderate (AAC >0 to ≤ 6), and severe AAC (AAC >6). Pulse pressure was used as a surrogate for arterial stiffness and examined as a secondary outcome. RESULTS: Among 2,418 participants, there was not a linear association between dietary potassium intake and AAC. Higher dietary potassium intake was associated with less severe AAC when comparing dietary potassium intake in Q2 with Q1 (odds ratio 0.55; 95% confidence interval: 0.34 to 0.92; P = .03). Higher dietary potassium intake was significantly associated with lower pulse pressure (P = .007): per 1000 mg/d higher dietary potassium intake, pulse pressure was 1.47 mmHg lower in the fully adjusted model. Compared to participants with dietary potassium intake in Q1, pulse pressure was 2.84 mmHg lower in Q4 (P = .04). CONCLUSIONS: We did not find a linear association between dietary potassium intake and AAC. Dietary potassium intake was negatively associated with pulse pressure.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Four-Day Food Record Macronutrient Intake, With and Without Biomarker Calibration, and Chronic Disease Risk in Postmenopausal Women.

We recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women's Health Initiative (1993-present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables.

Association of Sugar-Sweetened Beverage Consumption with Prediabetes and Glucose Metabolism Markers in Hispanic/Latino Adults in the United States: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Both the incidence of diabetes mellitus and consumption of sugar-sweetened beverages are high in the Hispanic/Latino population in the United States. The associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers in the diverse Hispanic/Latino population in the United States are unknown. OBJECTIVES: The objective of this study was to examine the cross-sectional associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers such as fasting glucose and insulin, 2-h oral-glucose-tolerance test, HOMA-IR, HOMA index for ß-cell function (HOMA-B), and glycated hemoglobin (HbA1c) among US Hispanic/Latino adults. METHODS: Using baseline data from the Hispanic Community Health Study/Study of Latinos (2008-2011), beverage consumption was ascertained using two 24-h dietary recalls and a food propensity questionnaire. Diabetes/prediabetes status was defined by self-report, antihyperglycemic medication use, and American Diabetes Association laboratory criteria. Among 9965 individuals without diabetes (5194 normoglycemia, 4771 prediabetes) aged 18-74 y, the associations of beverage consumption with prediabetes and glucose metabolism markers were analyzed using logistic and linear regressions, respectively, accounting for complex survey design. RESULTS: Compared with individuals who consumed <1 serving/d (<240 mL/d) of sugar-sweetened beverages, individuals who consumed >2 servings/d (>480 mL/d) had 1.3 times greater odds of having prediabetes (95% CI: 1.06, 1.61) and higher glucose metabolism markers including fasting glucose, fasting insulin, HOMA-IR, and HbA1c. Consumption of artificially sweetened beverages showed an inverse association with ß-cell function (HOMA-B). Intake of 100% fruit juice was not significantly associated with prediabetes nor with glucose metabolism markers. CONCLUSIONS: Among US Hispanic/Latino adults, higher sugar-sweetened beverage consumption was associated with increased odds of prediabetes and higher glucose metabolism markers. Public health initiatives to decrease sugar-sweetened beverage consumption could potentially reduce the burden of diabetes among Hispanics/Latinos in the United States.

Biomarkers for Components of Dietary Protein and Carbohydrate with Application to Chronic Disease Risk in Postmenopausal Women.

BACKGROUND: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, whereas protein density associations were mixed. OBJECTIVES: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber. METHODS: Prospective disease association analyses were undertaken in Women's Health Initiative (WHI) cohorts of postmenopausal US women, aged 50-79 y when enrolled at 40 US clinical centers. Biomarkers were developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-y (median) follow-up period, using HR regression methods. RESULTS: Previously reported elevations in cardiovascular disease (CVD) with higher-protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had an HR of 1.20 (95% CI: 1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with a 20% increment HR factor of 0.89 (95% CI: 0.83, 0.94). Cancer risk showed little association with fiber density, whereas diabetes risk had a 20% increment HR of 0.93 (95% CI: 0.88, 0.98) relative to the HRs for total carbohydrate density. CONCLUSIONS: In a population of postmenopausal US women, CVD risk was associated with high-animal-protein and low-fiber diets, cancer risk was associated with low-carbohydrate diets, and diabetes risk was associated with low-fiber/low-carbohydrate diets.

Mortality Associated with Healthy Eating Index Components and an Empirical-Scores Healthy Eating Index in a Cohort of Postmenopausal Women.

BACKGROUND: Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among the dietary variables and by scoring dietary variables empirically. OBJECTIVES: To relate Healthy Eating Index (HEI)-2010 components and total energy intake to all-cause and cause-specific mortality in Women's Health Initiative (WHI) cohorts and to define and evaluate an associated Empirical-Scores Healthy Eating Index (E-HEI). METHODS: Analyses are conducted in WHI cohorts (n = 67,247) of healthy postmenopausal women, aged 50-79 y, when enrolled during 1993-1998 at 40 US clinical centers, with embedded nutrition biomarker studies. Replicate food-frequency assessments for HEI-2010 ratio variables and doubly labeled water total energy assessments, separated by ∼6 mo, are used as response variables to jointly calibrate baseline dietary data to reduce measurement error influences, using 2 nutrition biomarker studies (n = 199). Calibrated dietary variables are associated with mortality risk, and an E-HEI is defined, using cross-validated HR regression estimation. RESULTS: Of 15 dietary variables considered, all but empty calories calibrated well. Ten variables related significantly (P < 0.05) to total mortality, with favorable fruit, vegetable, whole grain, refined grain, and unsaturated fat associations and unfavorable sodium, saturated fat, and total energy associations. The E-HEI had cross-validated total mortality HRs (95% CIs) of 0.87 (0.82, 0.93), 0.80 (0.76, 0.86), 0.77 (0.72, 0.82), and 0.74 (0.69, 0.79) respectively, for quintiles 2 through 5 compared with quintile 1. These depart more strongly from the null than do HRs for HEI-2010 quintiles, primarily because of total energy. CONCLUSIONS: Mortality among US postmenopausal women depends strongly on diet, as evidenced by a new E-HEI that differs substantially from earlier dietary pattern score specifications.

Associations of steps per day and step intensity with the risk of diabetes: the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

BACKGROUND: Higher levels of moderate-to-vigorous physical activity have been associated with a lower risk of diabetes, but less is known about how daily step counts (steps/day) are associated with diabetes risk. Therefore, we examined the association of steps/day and step intensity with incident diabetes. METHODS: We included 6634 adults from the population-based prospective cohort Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (2008-2017). Cox proportional hazard models that accounted for complex survey design and sampling weights were used to estimate the association of baseline accelerometer-assessed steps/day and step intensity with 6-year risk of incident diabetes as hazard ratios (HR) and 95% confidence intervals (CI). We further examined whether the percent of intense steps at a given accumulation of steps/day was associated with diabetes risk, and if associations were modified by specific cohort characteristics. RESULTS: The average age of cohort members was 39 years and 52% were female. Adults had an average of 8164 steps/day and spent 12 min/day in brisk ambulation (> 100 steps/min). Over 6 years of follow-up, there were 1115 cases of diabetes. There was a suggestive lower risk of diabetes with more steps/day- adults had a 2% lower risk per 1000 steps/day (HR = 0.98 (95% CI 0.95, 1.00)). Inverse associations between average steps/day and diabetes incidence were observed across many cohort characteristics, but most importantly among adults at high risk for diabetes - those who were older, or had obesity or prediabetes. Adults who accumulated 17 min/day in brisk ambulation compared to < 2 min/day had a 31% lower risk of diabetes (HR = 0.69 (95% CI 0.53, 0.89)). A greater percent of intense steps for a given accumulation of steps/day was associated with further risk reduction. CONCLUSION: Adults who accumulate more daily steps may have a lower risk of diabetes. Accumulating more steps/day and greater step intensity appear to be important targets for preventing diabetes.

Neighborhood built environments and Hispanic/Latino adults' physical activity in the U.S.: The Hispanic community health study/study of Latinos community and surrounding areas study.

Despite experiencing health inequities, less is known about neighborhood environments and physical activity among Hispanic/Latino adults compared to other populations. We investigated this topic in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanic/Latino adults in the San Diego, California area of the U.S. completed measures of overall moderate-to-vigorous physical activity (MVPA) via accelerometry and domain-specific MVPA via questionnaire at Visits 1 (2008-2011; n = 4086) and 2 (2014-2017; n = 1776), ~6 years apart. 800-m home neighborhood buffers were used to create objective measures of residential, intersection, and retail density, bus/trolley stops, greenness, parks, and recreation area at Visit 1. Regression models tested the association of each neighborhood feature with MVPA at Visit 1 and over 6 years, adjusting for individual characteristics and neighborhood socioeconomic deprivation. At Visit 1, those in neighborhoods with higher vs. lower retail density or recreation area (+1 vs. -1 standard deviation from the mean) engaged in 10% more overall MVPA and 12-22% more active transportation. Those in neighborhoods with higher vs. lower residential density engaged in 22% more active transportation. Those in neighborhoods with higher vs. lower greenness and park count engaged in 14-16% more recreational MVPA. Neighborhood features were unassociated with changes in MVPA over 6 years. Although changes in MVPA over time were similar across neighborhoods, Hispanic/Latino adults living in neighborhoods with design features supportive of walking and recreational activity (e.g., greater residential and retail density, more parks and recreation facilities) were consistently more active. Improving neighborhood environments appears important for supporting physical activity among Hispanic/Latino adults.

Association of sleep duration and insomnia with metabolic syndrome and its components in the Women's Health Initiative.

BACKGROUND: Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women's Health Initiative (WHI). METHODS: The study included postmenopausal women (ages 50-79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated. RESULTS: In cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12-2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01-1.40 and OR = 1.23; 95%CI 1.05-1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99-1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03-1.34 and OR = 1.17; 95%CI 1.02-1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01-1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08-2.03). CONCLUSIONS: Among postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.

Associations of sodium and potassium intake with chronic kidney disease in a prospective cohort study: findings from the Hispanic Community Health Study/Study of Latinos, 2008-2017.

BACKGROUND: According to dietary recommendations, reduction of sodium intake has potential to reduce Chronic Kidney Disease (CKD) risk; however the role of dietary potassium and the sodium -to- potassium ratio in the development of CKD is unclear. METHODS: We studied 9778 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from four US urban communities. Participants were aged 18-74 yrs., free from CKD at baseline in 2008-2011 and re-examined between 2014 and - 2017. Dietary intake of sodium, potassium and the ratio of dietary sodium -to- potassium were measured from two baseline 24-h dietary recalls. Incident CKD was defined as: 1) estimated glomerular filtration rate (eGFR) decline of 1 unit per year and eGFR < 60 ml/min/1.73m2 or 2) albumin to creatinine ratio ≥ 30 mg/g at the follow-up visit. We used multivariable survey weighted Poisson regression to estimate adjusted incident rates of incident CKD. RESULTS: At baseline, mean age was 41 years. Average follow up time was 6.2 years. From fully adjusted Poisson regression analyses, self-reported sodium intake was not associated with incident CKD. However, for each 500 mg decrement in potassium intake, there was an 11% increase risk of incident CKD (IRR = 1.11, 95% CI = 1.00, 1.24). Additionally, every 1 M ratio increment of sodium -to -potassium ratio was associated with a 21% increased risk of incident CKD (IRR = 1.21, 95% CI = 1.02, 1.45), p < 0.05). CONCLUSIONS: We conclude that diets low in potassium and high in sodium are associated with increased risk of developing chronic kidney disease among healthy US Hispanic/Latino adults.

Predictors of incident diabetes in two populations: framingham heart study and hispanic community health study / study of latinos.

BACKGROUND: Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly. METHODS: Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry. Among individuals without diabetes, Cox proportional hazards regression models (both age- and sex-adjusted, and then multivariable-adjusted for all candidate predictors) identified predictors of incident diabetes over a decade of follow-up, defined using clinical history or laboratory assessments. RESULTS: Four independent predictors were shared between FHS and HCHS/SOL. In each cohort, the multivariable-adjusted hazard of diabetes increased by approximately 50% for every ten-year increment of age and every five-unit increment of body mass index (BMI), and was 50-70% higher among hypertensive than among non-hypertensive individuals (all P < 0.01). Compared with full-time employment status, the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for part-time employment was 0.61 (0.37,1.00) in FHS and 0.62 (0.41,0.95) in HCHS/SOL. Moderate-to-vigorous physical activity (MVPA) was an additional predictor in common observed in age- and sex-adjusted models, which did not persist after adjustment for other covariates (compared with MVPA ≤ 5 min/day, HR for MVPA level ≥ 30 min/day was 0.48 [0.31,0.74] in FHS and 0.74 [0.56,0.97] in HCHS/SOL). Additional predictors found in sex- and age-adjusted analyses among the FHS participants included male gender and lower education, but these predictors were not found to be independent of others in multivariable adjusted models, nor were they associated with diabetes risk among HCHS/SOL adults. CONCLUSIONS: The same four independent predictors - age, body mass index, hypertension and employment status - were associated with diabetes risk across two disparate US populations. While the reason for elevated diabetes risk in full-time workers is unclear, the findings suggest that diabetes may be part of the work-related burden of disease. Our findings also support prior evidence that differences by gender and socioeconomic position in diabetes risk are not universally present across populations.

Marital Status and Gender Associated with Sleep Health among Hispanics/Latinos in the US: Results from HCHS/SOL and Sueño Ancillary Studies.

Poor sleep and different patterns of marital status among Hispanics/Latinos have been documented, yet the extent to which marital status is associated with sleep health and the moderating role of gender in this association among Hispanics/Latinos is poorly understood.Demographic and sleep data were obtained from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL: n= 16,415), an epidemiological cohort study, and the Sueño Study (n= 2,252) that is an ancillary to HCHS/SOL. Sleep duration, insomnia symptoms, daytime sleepiness, napping, and snoring were self-reported and drawn from HCHS/SOL. Sleep efficiency, sleep fragmentation, and inter-day stability were objectively assessed in the Sueño Study.Complex sample analyses indicated that being married or cohabiting was associated with better sleep health in general, including having normal sleep duration, fewer insomnia symptoms, and higher sleep efficiency (F> 2.804, p< .044). These associations were more prominent in objectively measured sleep indices and among females.Findings suggest being in a committed relationship associated with better sleep health in Hispanics/Latinos in the US, a diverse and under-represented population. Findings may have implications for tailoring sleep health interventions to at-risk populations who may less likely to be in a committed relationship.

Diet quality comparisons in Hispanic/Latino siblings: Results from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

The objective of this study was to determine how well Hispanic/Latino siblings' diet quality correlate with each other and whether social and environmental factors explained potential differences. Hispanic/Latino 8-16-year-olds from the cross-sectional Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth) with at least one sibling enrolled in the study were examined (n = 740). Diet quality was assessed with the Healthy Eating Index 2010 (HEI-2010), calculated from two 24-h recalls. Mixed effects models were used with HEI-2010 score as the outcome, and correlations in siblings' diet quality were assessed with intraclass correlation coefficients (ICCs). All models were examined stratified by age and sex. Diet-related social and environmental measures were added as fixed effects in a secondary analysis. Mean (standard deviation) overall HEI-2010 score was 53.8 (13.0). The ICC for siblings' HEI-2010 score was 0.31 (95% CI: 0.25, 0.38). Siblings who were born <3 vs. ≥3 years apart had stronger correlations in overall diet quality (0.47 [95% CI: 0.37, 0.58] vs. 0.21 [95% CI: 0.13, 0.30]), but no differences were observed in overall HEI-2010 score according to sex. Greater peer support for fruit and vegetable intake (ß = 1.42 [95% CI: 0.62, 2.21]) and greater away-from-home food consumption (ß = -1.24 [95% CI: -2.15, -0.32]) were associated with differences in siblings' diet quality. Overall diet quality scores of Hispanic/Latino siblings in this study were slightly correlated, with stronger correlations among siblings closer in age. Differences in peer support and foods consumed outside the home may explain differences in siblings' diet quality. Future research should investigate additional determinants of differences in siblings' diets.