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Background: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake., Objectives: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults., Methods: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study (ARIC; n = 3776). Results from the 2 subgroups were meta-analyzed using fixed effects meta-analysis. Significant meta-analyzed associations in the ARIC study were then tested in the Bogalusa Heart Study (BHS; n = 785)., Results: In the ARIC study and BHS, the mean age was 54 and 48 years, 61% and 29% were Black, and the mean dairy intake was 1.7 and 1.3 servings/day, respectively. Twenty-nine significant associations between dietary intake of dairy and serum metabolites were identified in the ARIC study (total dairy, n = 14; low-fat dairy, n = 10; high-fat dairy, n = 5). Three associations were also significant in BHS: myristate (14:0) was associated with high-fat dairy, and pantothenate was associated with total dairy and low-fat dairy, but 23 of the 27 associations significant in the ARIC study and tested in BHS were not associated with dairy in BHS., Conclusions: We identified metabolomic associations with dietary intake of dairy, including 3 associations found in 2 independent cohort studies. These results suggest that myristate (14:0) and pantothenate (vitamin B5) are candidate biomarkers of dairy consumption., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults., Methods and Results: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%)., Conclusions: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs <3%), and protein (27% vs <3%). FMF infants are more likely to have an early introduction (<12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis., (Copyright © 2022 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Data are limited regarding differential and common effects of cardiovascular risk factors on subclinical changes in vascular structure and function. We aimed to examine the relationships of life-course cumulative burdens of cardiovascular risk factors with adult arterial pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) in a longitudinal cohort of the Bogalusa Heart Study., Methods: The cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors., Results: Adjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β] = 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β = 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β = 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β = 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups., Conclusions: The life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: To examine the associations between history of gestational diabetes mellitus (GDM) and breastfeeding with branched-chain amino acids (BCAA) and their metabolites in later life., Methods and Results: 638 women (mean age 48.0 y) who had participated in the Bogalusa Heart Study and substudies of pregnancy history had untargeted, ultrahigh performance liquid chromatography-tandem mass spectroscopy conducted by Metabolon© on serum samples. Metabolites were identified that were BCAA or associated with BCAA metabolic pathways. History of GDM at any pregnancy (self-reported, confirmed with medical records when possible) as well as breastfeeding were examined as predictors of BCAA using linear models, controlling for age, race, BMI, waist circumference, and menopausal status. None of the BCAA differed statistically by history of either GDM or breastfeeding, although absolute levels of each of the BCAA were higher with GDM and lower with breastfeeding. Of the 27 metabolites on the leucine, isoleucine and valine metabolism subpathway, 1-carboxyethylleucine, 1-carboxyethyvaline, and 3-hydroxy-2-ethylpropionate were higher in women with a history of GDM, but lower in women in women with a history of breastfeeding. Similar results were found for alpha-hydroxyisocaproate, 1-carboxyethylisoleucine, and N-acetylleucine., Conclusions: GDM and breastfeeding are associated in opposite directions with several metabolites on the BCAA metabolic pathway., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing., Methods: Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use., Results: Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change., Conclusions: EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits., Objectives: The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait., Methods: We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963)., Results: In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095)., Conclusions: Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle., (Copyright © American Society for Nutrition 2019.)

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants (N = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ± 3.8 years vs. 9.4 ± 3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The influence of childhood health on later-life health outcomes is increasingly hypothesized but rarely tested. We examined the relationship between cardiometabolic indicators in childhood and risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes., Methods: Childhood measurements from 755 women in the Bogalusa Heart Study included body mass index, systolic and diastolic blood pressure (SBP and DBP), low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, insulin, and glucose. Average childhood values were estimated by area under the curve computed from longitudinal quadratic random-effects growth models to account for the unequally spaced repeated measures. Women reported pregnancy complications, and medical records were linked to interview data where possible. Log-Poisson models predicted adjusted risk associated with an interquartile range increase in cardiometabolic indicators., Results: Elevated childhood insulin was associated with 10%-15% increased risk across the three outcomes. Elevated childhood SBP was associated with preeclampsia (SBP RR = 1.50, 95% CI: 1.13, 2.01) and SBP, DBP, and body mass index predicted pregnancy-induced hypertension (SBP RR = 2.15, 95% CI: 1.65, 2.82; DBP RR = 1.83, 95% CI: 1.38, 2.43; BMI RR = 1.67, 95% CI: 1.41, 1.98). Blood pressure mediated the association between childhood body mass index and pregnancy-induced hypertension., Conclusions: Results suggest the potential long-term impact of early-life cardiometabolic profiles on complications of pregnancy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to examine whether a history of asthma from childhood is associated with left ventricular (LV) mass in adulthood., Background: Asthma has been related to various cardiovascular risk factors affecting LV hypertrophy. The authors saw a need for a prospective study to analyze the relationship between a history of asthma from childhood and markers of LV mass among asymptomatic young adults., Methods: Prospective analyses were performed among 1,118 Bogalusa Heart Study participants (average age at follow-up 36.7 ± 5.1 years), with a baseline history of self-reported asthma collected since childhood (average age at baseline 26.8 ± 10.1 years). LV mass (g) was assessed using 2-dimensional guided M-mode echocardiography and was indexed for body height (m 2.7 ) as LV mass index (LVMI; g/m 2.7 ). A multivariate linear mixed model was fitted for the repeated measures., Results: After an average of 10.4 ± 7.5 years of follow-up, participants with a history of asthma from childhood had a greater LV mass (167.6 vs. 156.9; p = 0.01) and LVMI (40.7 vs. 37.7; p < 0.01) with adjustment for age, sex, race, smoking status, antihypertensive medication, heart rate, and systolic blood pressure (SBP). The difference of LVMI between group with asthma and the group without asthma remained significant after additional adjustment for body mass index (39.0 vs. 37.1; p = 0.03) and high-sensitivity C-reactive protein (38.4 vs. 36.6; p = 0.04). In addition, the authors found significant interactions between SBP and asthma on LV mass and LVMI (p for interaction <0.01, respectively). The associations between asthma and LV measures appeared to be stronger among pre-hypertensive and hypertensive participants (SBP ≥130 mm Hg) compared with participants with normal SBP (<130 mm Hg) (regression coefficient: 39.5 vs. 2.3 for LV mass and 9.0 vs. 0.9 for LVMI)., Conclusions: The findings of this study indicate that a history of asthma is associated with higher LVMI, and this association is stronger among participants with pre-hypertension and hypertension., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The relationship between dietary macronutrient composition and appetite is controversial. We examined the effects of a year-long low-carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite., Methods and Results: A total of 148 adults with a body mass index 30-45 kg/m(2), who were free of diabetes, cardiovascular disease and chronic kidney disease at baseline were randomly assigned to either a low-carbohydrate diet (carbohydrate [excluding dietary fiber]<40 g/day; N = 75) or a low-fat diet (<30% energy from fat, <7% from saturated fat; N = 73). Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity. Appetite and appetite-related hormones were measured at 0, 3, 6 and 12 months of intervention. At 12 months, mean changes (95% CI) in peptide YY were -34.8 pg/mL (-41.0 to -28.6) and in the low-carbohydrate group and -44.2 pg/mL (-50.4 to -38.0) in the low-fat group (net change: 9.54 pg/mL [0.6 to 18.2]; p = 0.036). Approximately 99% of dietary effects on peptide YY are explained by differences in dietary macronutrient content. There was no difference in change in ghrelin or self-reported change in appetite between the groups., Conclusions: A low-fat diet reduced peptide YY more than a low-carbohydrate diet. These findings suggest that satiety may be better preserved on a low-carbohydrate diet, as compared to a low fat diet., Trial Registration: clinicaltrials.gov Identifier: NCT00609271., (Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Left ventricular (LV) hypertrophy increases the risk of future cardiovascular events. The relationship between obesity in young adulthood and later LV geometry is unknown. We examined the association between long-term changes in measures of adiposity and subsequent LV geometry among 1073 young adults from the Bogalusa Heart Study., Methods and Results: Echocardiography-measured LV geometry was classified into normal (N = 796), concentric remodeling (N = 124), eccentric hypertrophy (N = 99), and concentric hypertrophy (N = 54) by integrating relative wall thickness and LV mass index. The mean age of our population was 38 years when the LV geometry was measured. Body mass index (BMI) increased by a mean of 4.9 kg/m(2) over a median of 20 years, waist circumference (WC) by 10.9 cm over 17 years, waist/hip ratio by 0.02 over 10 years, waist/height ratio by 0.06 over 17 years, abdominal height by 0.9 cm over 10 years, body fat (BF) percentage by 12.7% over 20 years, and Visceral Adiposity Index by 0.30 over 17 years. In polytomous logistic regression models corrected for multiple comparisons, participants with one-standard-deviation increases in BMI, WC, waist/height ratio, and BF had 2.00 (95% confidence interval (CI): 1.53-2.61), 1.33 (1.06-1.68), 1.35 (1.07-1.70), and 1.60 (1.26-2.03) times the risk of eccentric hypertrophy, respectively, after adjustment for demographic, lifestyle, metabolic risk factors, and follow-up time. Likewise, the rates of change in BMI, WC, waist/height ratio, and BF were associated with eccentric hypertrophy. There was no association with concentric remodeling or concentric hypertrophy., Conclusions: Our findings suggest that increases in BMI, WC, waist/height ratio, and BF were strong predictors of eccentric hypertrophy in middle age., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: Obesity is an important public health issue because of its high prevalence and concomitant increase in risk of cardiovascular diseases. Low carbohydrate diets are popular for weight loss and weight management but are not recommended in leading guidelines due to the perception that increases in dietary fat intake may lead to an adverse cardiovascular risk profile. To clarify the effects of a low-carbohydrate diet for weight loss on cardiovascular disease risk factors as compared to a low fat diet for weight loss, we systematically reviewed data from randomized controlled clinical trials and large observational studies., Data Synthesis: We searched the MEDLINE database (Jan 1966-Nov 2013) to identify studies that examined a low-carbohydrate diet as compared to a low-fat diet for weight loss or the improvement of cardiovascular disease risk factors., Conclusions: Recent randomized controlled trials document that low-carbohydrate diets not only decrease body weight but also improve cardiovascular risk factors. In light of this evidence from randomized controlled trials, dietary guidelines should be re-visited advocating a healthy low carbohydrate dietary pattern as an alternative dietary strategy for the prevention of obesity and cardiovascular disease risk factors., (Copyright © 2014. Published by Elsevier B.V.)

Background and Aims: Studies evaluating the effect of legume consumption on cholesterol have focused on soybeans, however non-soy legumes, such as a variety of beans, peas, and some seeds, are commonly consumed in Western countries. We conducted a meta-analysis of randomized controlled trials evaluating the effects of non-soy legume consumption on blood lipids., Methods and Results: Studies were retrieved by searching MEDLINE (from January 1966 through July 2009), EMBASE (from January 1980 to July 2009), and the Cochrane Collaboration's Central Register of Controlled Clinical Trials using the following terms as medical subject headings and keywords: fabaceae not soybeans not isoflavones and diet or dietary fiber and cholesterol or hypercholesterolemia or triglycerides or cardiovascular diseases. Bibliographies of all retrieved articles were also searched. From 140 relevant reports, 10 randomized clinical trials were selected which compared a non-soy legume diet to control, had a minimum duration of 3 weeks, and reported blood lipid changes during intervention and control. Data on sample size, participant characteristics, study design, intervention methods, duration, and treatment results were independently abstracted by 2 investigators using a standardized protocol. Data from 10 trials representing 268 participants were examined using a random-effects model. Pooled mean net change in total cholesterol for those treated with a legume diet compared to control was -11.8 mg/dL (95% confidence interval [CI], -16.1 to -7.5); mean net change in low-density lipoprotein cholesterol was -8.0mg/dL (95% CI, -11.4 to -4.6)., Conclusion: These results indicate that a diet rich in legumes other than soy decreases total and LDL cholesterol., (Copyright © 2009 Elsevier B.V. All rights reserved.)