Publications by authors named "Alexis C Wood"

55 Publications

Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations.

Commun Biol 2021 07 28;4(1):918. Epub 2021 Jul 28.

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.

Long chain polyunsaturated fatty acids (LC-PUFAs) have critical signaling roles that regulate dyslipidemia and inflammation. Genetic variation in the FADS gene cluster accounts for a large portion of interindividual differences in circulating and tissue levels of LC-PUFAs, with the genotypes most strongly predictive of low LC-PUFA levels at strikingly higher frequencies in Amerind ancestry populations. In this study, we examined relationships between genetic ancestry and FADS variation in 1102 Hispanic American participants from the Multi-Ethnic Study of Atherosclerosis. We demonstrate strong negative associations between Amerind genetic ancestry and LC-PUFA levels. The FADS rs174537 single nucleotide polymorphism (SNP) accounted for much of the AI ancestry effect on LC-PUFAs, especially for low levels of n-3 LC-PUFAs. Rs174537 was also strongly associated with several metabolic, inflammatory and anthropomorphic traits including circulating triglycerides (TGs) and E-selectin in MESA Hispanics. Our study demonstrates that Amerind ancestry provides a useful and readily available tool to identify individuals most likely to have FADS-related n-3 LC-PUFA deficiencies and associated cardiovascular risk.
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http://dx.doi.org/10.1038/s42003-021-02431-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319323PMC
July 2021

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.

Circ Genom Precis Med 2021 Aug 16;14(4):e003288. Epub 2021 Jul 16.

Department of Clinical Epidemiology (R.L.G., D.O.M.-K., F.R.R., R.dM.), Leiden University Medical Center, the Netherlands.

Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the locus and dyslipidemia.

Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.

Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; <0.0001), but not significantly among the lowest SSB consumers (=0.81; <0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (β, 0.06 [95% CI, 0.02-0.09] ln-mg/dL per allele, =0.001) but not the lowest SSB consumers (=0.84; =0.0005).

Conclusions: Our results identified genetic variants in the locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.
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http://dx.doi.org/10.1161/CIRCGEN.120.003288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373451PMC
August 2021

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Metabolites 2021 Jun 26;11(7). Epub 2021 Jun 26.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (prediabetes or newly diagnosed diabetes). In separate models, reduced insulin sensitivity, reduced disposition index, and reduced insulin clearance were associated with dysglycemia. In a joint model, only insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with insulin sensitivity, disposition index, or three insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.
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http://dx.doi.org/10.3390/metabo11070420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304591PMC
June 2021

Improvement in Total and Face-to-Face Provider Time in a Multidisciplinary Craniofacial Team Clinic: An Interventional Study.

Cleft Palate Craniofac J 2021 Jun 24:10556656211021705. Epub 2021 Jun 24.

Department of Pediatrics, The 22796Children's Hospital of San Antonio, Baylor College of Medicine, San Antonio, TX, USA.

Objective: Identify factors contributing to time a family spends in a Multidisciplinary Craniofacial Team Clinic (MDCT) and implement an intervention to reduce this time.

Design: Interventional: a restructuring of clinics to serve those patients requiring fewer provider encounters separately.

Setting: An American Cleft Palate-Craniofacial Association-accredited MDCT in an academic children's hospital.

Patients/participants: One hundred sixty-seven patients with craniofacial diagnoses.

Interventions: Time data were tabulated over ∼2 years. Following 9 months of data collection, patients requiring fewer provider encounters were scheduled to a separate clinic serving children with craniosynostosis, and data were collected in the same fashion for another 14 months.

Main Outcome Measures: Principal outcome measures included total visit time and proportion of the visit spent without a provider in the room before and after clinic restructuring.

Results: The average time spent by family in a clinic session was 161.53 minutes, of which 64.3% was spent without a provider in the room. Prior to clinic restructuring, a greater number of provider encounters was inversely associated with percentage of time spent without a provider ( < .001). Upon identifying this predictor, scheduling patients who needed fewer provider encounters to a Craniosynostosis Clinic session resulted in reduction in absolute and percentage of time spent without a provider ( < .001).

Conclusions: The number of provider encounters is a significant predictor of the proportion of a clinic visit spent without a provider. Clinic restructuring to remove patient visits that comprise fewer provider encounters resulted in a greater percentage of time spent with a provider in an MDCT.
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http://dx.doi.org/10.1177/10556656211021705DOI Listing
June 2021

Gadolinium is not necessary for surveillance MR imaging in children with chiasmatic-hypothalamic low-grade glioma.

Pediatr Blood Cancer 2021 Oct 16;68(10):e29178. Epub 2021 Jun 16.

Department of Pediatrics, Division of Radiology, Texas Children's Hospital, Houston, Texas.

Background: Patients with chiasmatic-hypothalamic low-grade glioma (CHLGG) have frequent MRIs with gadolinium-based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in the brains of children is a potential concern. The purpose of this study is to evaluate whether MRI with GBCA is necessary for determining radiographic tumor progression in children with CHLGG.

Methods: Children who were treated for progressive CHLGG from 2005 to 2019 at Texas Children's Cancer Center were identified. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three dimensional measurements and tumor characteristics were evaluated. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared with baseline or best response after initiation of therapy.

Results: A total of 28 patients with progressive CHLGG were identified with a total of 683 MRIs with GBCA reviewed (mean 24 MRIs/patient; range, 11-43 MRIs). Radiographic progression was observed 92 times, 91 (99%) on noncontrast and 90 (98%) on contrast imaging. Sixty-seven progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (99%) contrast sequences. Tumor growth > 2 mm in any dimension was identified in 184/187 (98%) noncontrast and 181/187 (97%) with contrast imaging. Metastatic tumors were better visualized on contrast imaging in 4/7 (57%).

Conclusion: MRI without GBCA effectively identifies patients with progressive disease. When imaging children with CHLGG, eliminating GBCA should be considered unless monitoring patients with metastatic disease.
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http://dx.doi.org/10.1002/pbc.29178DOI Listing
October 2021

Challenges in Feeding Children Posed by the COVID-19 Pandemic: a Systematic Review of Changes in Dietary Intake Combined with a Dietitian's Perspective.

Curr Nutr Rep 2021 09;10(3):155-165

USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1000 Bates Street, Houston, TX, 77071, USA.

Purpose Of Review: To examine the evidence that the dietary quality of children changed between the period preceding the COVID-19 pandemic and the first year during the pandemic.

Recent Findings: A systematic review of the evidence for dietary changes occurring as a result of the pandemic-related restrictions, in Part I of this article, yielded 38 original research articles. These articles had conflicting results, some describing improvements in overall quality and some describing deteriorations. As a whole the studies were characterized by a low study quality, and children were poorly represented. Taken together, these studies do not provide enough evidence to draw conclusions about whether dietary habits changed or not as a result of the pandemic. However, in a wider, narrative review of the psychosocial changes occurring as a result of the COVID-19 pandemic, and the known associations of these factors with a dietary intake in Part II, we conclude that there is a reason to expect that the dietary quality of children might have been adversely affected by the COVID-19 pandemic. One the one hand, the literature fails to provide conclusive evidence on changes in the dietary quality of children resulting from the COVID-19 pandemic. On the other hand, the broader literature supports the hypothesis that children's dietary quality will have declined during the pandemic. Taken together, we urgently need more high-quality research on children's changes in dietary intake occurring over the pandemic. This will provide important information on whether any potential long-term consequences of such changes, if they exist, need to be examined and ameliorated.
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http://dx.doi.org/10.1007/s13668-021-00359-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123103PMC
September 2021

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

Rationale and design of the Baylor Infant Twin Study-A study assessing obesity-related risk factors from infancy.

Obes Sci Pract 2021 Feb 11;7(1):63-70. Epub 2020 Nov 11.

Department of Pediatrics USDA/ARS Children's Nutrition Research Center Baylor College of Medicine Houston Texas USA.

Background: Early childhood (0-3 years) is a critical period for obesity prevention, when tendencies in eating behaviors and physical activity are established. Yet, little is understood about how the environment shapes children's genetic predisposition for these behaviors during this time. The Baylor Infant Twin Study (BITS) is a two phase study, initiated to study obesity risk factors from infancy. Data collection has been completed for Phase 1 in which three sub-studies pilot central measures for Phase 2. A novel infant temperament assessment, based on observations made by trained researchers was piloted in (BOPP) study, a new device for measuring infant feeding parameters (the "orometer") in the (BIO), and methods for analyzing DNA methylation in twins of unknown chorionicity in

Methods: EpiTwin was a cross-sectional study of neonatal twins, while up to three study visits occurred for the other studies, at 4- (BOPP, BIO), 6- (BOPP), and 12- (BOPP, BIO) of age. Measurements for BOPP and BIO included temperament observations, feeding observations, and body composition assessments while EpiTwin focused on collecting samples of hair, urine, nails, and blood for quantifying methylation levels at 10 metastable epialleles. Additional data collected include demographic information, zygosity, chorionicity, and questionnaire-based measures of infant behaviors.

Results: Recruitment for all three studies was completed in early 2020. EpiTwin recruited 80 twin pairs (50% monochorionic), 31 twin pairs completed the BOPP protocol, and 68 singleton infants participated in BIO.

Conclusions: The psychometric properties of the data from all three studies are being analyzed currently. The resulting findings will inform the development of the full BITS protocol, with the goal of completing assessments at 4-, 6-, 12-, and 14-month of age for 400 twin pairs.
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http://dx.doi.org/10.1002/osp4.463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909590PMC
February 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 05 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

On the joint role of non-Hispanic Black race/ethnicity and weight status in predicting postmenopausal weight gain.

PLoS One 2021 1;16(3):e0247821. Epub 2021 Mar 1.

Department of Epidemiology and Prevention, Wake Forest School of Medicine, Wake Forest, NC, United States of America.

Objectives: To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs).

Methods: Data were included from 70,750 NHW and NHB postmenopausal women from the Women's Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline.

Results: In both crude and adjusted models, NHBs were more likely to experience ≥10% weight gain than NHWs within the same category of baseline weight status. Moreover, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain in both crude and adjusted models. Age-stratified results were consistent with overall findings. In all age categories, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain. Based on the results of adjusted models, the joint influence of NHB race/ethnicity and weight status on risk of postmenopausal weight gain was both sub-additive and sub-multiplicative.

Conclusion: NHBs are more likely to experience postmenopausal weight gain than NHWs, and the disparity in risk is most pronounced among those who are normal weight at baseline. To address the disparity in postmenopausal obesity, future studies should focus on identifying and modifying factors that promote weight gain among normal weight NHBs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247821PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920337PMC
March 2021

Macro and micro sleep architecture and cognitive performance in older adults.

Nat Hum Behav 2021 01 16;5(1):123-145. Epub 2020 Nov 16.

Harvard Medical School, Boston, MA, USA.

We sought to determine which facets of sleep neurophysiology were most strongly linked to cognitive performance in 3,819 older adults from two independent cohorts, using whole-night electroencephalography. From over 150 objective sleep metrics, we identified 23 that predicted cognitive performance, and processing speed in particular, with effects that were broadly independent of gross changes in sleep quality and quantity. These metrics included rapid eye movement duration, features of the electroencephalography power spectra derived from multivariate analysis, and spindle and slow oscillation morphology and coupling. These metrics were further embedded within broader associative networks linking sleep with aging and cardiometabolic disease: individuals who, compared with similarly aged peers, had better cognitive performance tended to have profiles of sleep metrics more often seen in younger, healthier individuals. Taken together, our results point to multiple facets of sleep neurophysiology that track coherently with underlying, age-dependent determinants of cognitive and physical health trajectories in older adults.
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http://dx.doi.org/10.1038/s41562-020-00964-yDOI Listing
January 2021

Prevalence of Adrenal Insufficiency and Glucocorticoid Use in Pediatric Pseudotumor Cerebri Syndrome.

J Neuroophthalmol 2020 Oct 26. Epub 2020 Oct 26.

Department of Pediatrics, Section of Pediatric Diabetes and Endocrinology (AH-M, VEH), Baylor College of Medicine | Texas Children's Hospital, Houston, Texas; USDA/ARS Children's Nutrition Research Center (ACW), Houston, Texas; Department of Ophthalmology (VS), Baylor College of Medicine, Houston, Texas; Cincinnati Children's Hospital Medical Center (VS), Abrahamson Pediatric Eye Institute/Division of Pediatric Ophthalmology, Cincinnati, Ohio; and Department of Ophthalmology (VS), University of Cincinnati, Cincinnati, Ohio.

Background: The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship.

Methods: We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-μg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol <16 μg/dL and AM cortisol <5 μg/dL), (2) at risk (peak cortisol 16-20 μg/dL, AM cortisol 5-13 μg/dL, or random <13 μg/dL), or (3) sufficient (peak cortisol >20 μg/dL and AM or random cortisol >13 μg/dL).

Results: A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test.

Conclusions: Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.
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http://dx.doi.org/10.1097/WNO.0000000000001111DOI Listing
October 2020

Rationale, design and baseline characteristics of the Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Diabetes Obes Metab 2020 11 20;22(11):1976-1984. Epub 2020 Aug 20.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Aim: To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D).

Materials And Methods: The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline.

Results: After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance.

Conclusions: The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.
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http://dx.doi.org/10.1111/dom.14145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444996PMC
November 2020

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med 2020 06 12;17(6):e1003102. Epub 2020 Jun 12.

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).

Methods And Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.

Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292352PMC
June 2020

Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality.

Circ Genom Precis Med 2020 08 11;13(4):e002766. Epub 2020 Jun 11.

The Cardiovascular Health Research Unit, University of Washington, Seattle, WA (S.A.G., N.S., J.A.B., C.M.S.).

Background: DNA methylation patterns associated with habitual diet have not been well studied.

Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.

Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected <1.6×10). Hypermethylation of cg18181703 () was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (=5.7×10). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR <4.5×10). For example, hypermethylation of cg11250194 () was associated with lower triglyceride concentrations (MR, =1.5×10).and hypermethylation of cg02079413 (; ) was associated with body mass index (corrected MR, =1×10).

Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.
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http://dx.doi.org/10.1161/CIRCGEN.119.002766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442697PMC
August 2020

Phenotypic and Genetic Characterization of Lower LDL Cholesterol and Increased Type 2 Diabetes Risk in the UK Biobank.

Diabetes 2020 10 3;69(10):2194-2205. Epub 2020 Jun 3.

U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX.

Although hyperlipidemia is traditionally considered a risk factor for type 2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL cholesterol (LDL-C) increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (odds ratio 0.41 [95% CI 0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank ( = 431,167) and the Global Lipids Genetics Consortium ( = 188,577), and data on T2D from the Diabetes Genetics Replication and Meta-Analysis consortium ( = 898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and nine have previously been implicated in nonalcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C-lowering medications.
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http://dx.doi.org/10.2337/db19-1134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506834PMC
October 2020

Caregiver Influences on Eating Behaviors in Young Children: A Scientific Statement From the American Heart Association.

J Am Heart Assoc 2020 05 11;9(10):e014520. Epub 2020 May 11.

A substantial body of research suggests that efforts to prevent pediatric obesity may benefit from targeting not just a child eats, but they eat. Specifically, child obesity prevention should include a component that addresses reasons why children have differing abilities to start and stop eating in response to internal cues of hunger and satiety, a construct known as . This review summarizes current knowledge regarding how caregivers can be an important influence on children's eating self-regulation during early childhood. First, we discuss the evidence supporting an association between caregiver feeding and child eating self-regulation. Second, we discuss what implications the current evidence has for actions caregivers may be able to take to support children's eating self-regulation. Finally, we consider the broader social, economic, and cultural context around the feeding environment relationship and how this intersects with the implementation of any actions. As far as we are aware, this is the first American Heart Association (AHA) scientific statement to focus on a psychobehavioral approach to reducing obesity risk in young children. It is anticipated that the timely information provided in this review can be used not only by caregivers within the immediate and extended family but also by a broad range of community-based care providers.
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http://dx.doi.org/10.1161/JAHA.119.014520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660848PMC
May 2020

Methylphenidate improves weight control in childhood brain tumor survivors with hypothalamic obesity.

Pediatr Blood Cancer 2020 07 8;67(7):e28379. Epub 2020 May 8.

Division of Diabetes and Endocrinology, Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.

Background: Hypothalamic obesity causes unrelenting weight gain for childhood brain tumor survivors. No single therapy has proven effective for treatment. We aimed to evaluate effectiveness of long-term methylphenidate therapy on body mass index (BMI) change in children with hypothalamic obesity.

Methods: A retrospective analysis included children with a history of brain tumor and hypothalamic obesity receiving methylphenidate (10-60 mg/day) for hypothalamic obesity. Subjects were evaluated for BMI trajectory before and after methylphenidate start. Given that z-scores can be skewed in severely obese children, we calculated BMI as a percent of the BMI at the 95th percentile for the child's age and gender (BMI% 95th).

Results: Twelve patients with hypothalamic obesity completed methylphenidate therapy for at least 6 months (median 3.1 years, range 1.0-5.8 years). All subjects had a suprasellar tumor (nine [75%] with craniopharyngioma) and pituitary dysfunction. Pretreatment median BMI percent of the 95th percentile was 125.6% (interquartile range [IQR] 25-75: 115.3-138.3%) with BMI z-score of 2.4 (IQR 25-75: 2.1-2.6). Following methylphenidate treatment, there was a 69.9% reduction in the median slope of BMI change. Eleven of 12 patients (92%) had a reduction in the slope of their BMI change on methylphenidate treatment. Postmethylphenidate median BMI percent of the 95th percentile decrease to 115.2% (IQR 25-75: 103.6-121.2%) with median BMI z-score of 2.1 (IQR 25-75: 1.8-2.2). Mild side effects were noted in six patients.

Conclusions: Methylphenidate use reduced and sustained BMI change in children with hypothalamic obesity. Stimulant therapy is an effective first-line agent for treatment of hypothalamic obesity.
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http://dx.doi.org/10.1002/pbc.28379DOI Listing
July 2020

Salivary AMY1 Copy Number Variation Modifies Age-Related Type 2 Diabetes Risk.

Clin Chem 2020 05;66(5):718-726

USDA Agricultural Research Service, Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

Background: Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain.

Methods: We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk.

Results: We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR.

Conclusions: We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.
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http://dx.doi.org/10.1093/clinchem/hvaa072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192522PMC
May 2020

Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

Genet Epidemiol 2020 03 12;44(2):208-217. Epub 2019 Dec 12.

Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.

25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n = 1,099) or European (n = 8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p = 3.3 × 10 , p =  2.1 × 10 , and p =  2.4 × 10 , respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D ( >20 ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p = .018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.
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http://dx.doi.org/10.1002/gepi.22272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028464PMC
March 2020

Ancestry-specific polygenic scores and SNP heritability of 25(OH)D in African- and European-ancestry populations.

Hum Genet 2019 Oct 24;138(10):1155-1169. Epub 2019 Jul 24.

Department of Population Health Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, 53706, USA.

Vitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D has been discovered. Therefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of downstream morbidity and mortality. Using PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors in those of European (n = 9569) or African ancestry (n = 2761) from three cohort studies. The PGS for African ancestry was derived using all input SNPs (a p value cutoff of 1.0) and had an R of 0.3%; for European ancestry, the optimal PGS used a p value cutoff of 3.5 × 10 in the target/tuning dataset and had an R of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/mL lower than those with lowest genetic risk (p = 0.0463-3.2 × 10), requiring an additional 467-500 IU of vitamin D intake to maintain equivalent 25(OH)D. PGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.
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http://dx.doi.org/10.1007/s00439-019-02049-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041489PMC
October 2019

Genetic overlap between executive functions and BMI in childhood.

Am J Clin Nutr 2019 10;110(4):814-822

Department of Psychology, University of Texas at Austin, Austin, TX, USA.

Background: Executive functions (EFs) comprise a group of cognitive processes that selectively control and regulate attention. Inverse relations have been reported between EFs and BMI. However, the mechanisms underlying this association are not well understood.

Objectives: We aimed to decompose the inverse relation between EFs and BMI into genetic and environmental components.

Methods: We employed a cross-sectional analysis of data from 869 twins aged 7-15 y from the Texas Twin Project, who completed a neuropsychological test battery measuring 4 EFs (switching, inhibitory control, working memory, and updating); academic achievement (reading and mathematics); and general cognitive abilities (general intelligence/intelligence quotient; crystallized and fluid intelligence; and processing speed). Participants also had their height and weight measured.

Results: After controlling for age, sex, and race/ethnicity, BMI was inversely associated with a general EF factor representing the capacity to control and regulate goal-oriented behaviors (r = -0.125; P = 0.01; Q = 0.04). This inverse BMI-EF association was due to a significant overlap in genetic factors contributing to each phenotype (genetic correlation, rA, = -0.15; P < 0.001). Shared genetic influences accounted for 80% of the phenotypic association.

Conclusions: Children with higher general EF have lower BMIs, and this association is primarily attributable to shared genetic influences on both phenotypes. The results emphasize that higher weight associates not only with physical sequelae, but also with important cognitive attributes. This work adds to a growing body of research suggesting there are sets of genetic variants common across physical health and cognitive functioning.
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http://dx.doi.org/10.1093/ajcn/nqz109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766443PMC
October 2019

Metabolomic Insights into the Effects of Breast Milk Versus Formula Milk Feeding in Infants.

Curr Nutr Rep 2019 09;8(3):295-306

USDA / ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, TX, 77030, USA.

Purpose Of Review: This review summarizes the latest scientific evidence for the presence of metabolomic differences between infants fed breast milk (I-BM) and infants fed formula milk (I-FM).

Recent Findings: Across the studies included in this review, a total of 261 metabolites were analyzed, of which 151 metabolites were reported as significantly associated with infant feeding modality (BM versus FM). However, taken as a whole, the relevant literature was notable both for methodological limitations, such as small sample sizes, and heterogeneity between the studies. This may be why many associations between infant metabolite profile and feeding modality have not replicated across studies. To our knowledge, this is the first review to integrate the available literature on metabolomic differences between I-BM versus I-FM. This narrative review synthesized the data across studies and identified those metabolites which show the most robust associations with infant feeding modality. Methodological limitations of the current studies are identified, followed by recommendations for how to address these in future studies.
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http://dx.doi.org/10.1007/s13668-019-00284-2DOI Listing
September 2019

A genomic atlas of systemic interindividual epigenetic variation in humans.

Genome Biol 2019 06 3;20(1):105. Epub 2019 Jun 3.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Background: DNA methylation is thought to be an important determinant of human phenotypic variation, but its inherent cell type specificity has impeded progress on this question. At exceptional genomic regions, interindividual variation in DNA methylation occurs systemically. Like genetic variants, systemic interindividual epigenetic variants are stable, can influence phenotype, and can be assessed in any easily biopsiable DNA sample. We describe an unbiased screen for human genomic regions at which interindividual variation in DNA methylation is not tissue-specific.

Results: For each of 10 donors from the NIH Genotype-Tissue Expression (GTEx) program, CpG methylation is measured by deep whole-genome bisulfite sequencing of genomic DNA from tissues representing the three germ layer lineages: thyroid (endoderm), heart (mesoderm), and brain (ectoderm). We develop a computational algorithm to identify genomic regions at which interindividual variation in DNA methylation is consistent across all three lineages. This approach identifies 9926 correlated regions of systemic interindividual variation (CoRSIVs). These regions, comprising just 0.1% of the human genome, are inter-correlated over long genomic distances, associated with transposable elements and subtelomeric regions, conserved across diverse human ethnic groups, sensitive to periconceptional environment, and associated with genes implicated in a broad range of human disorders and phenotypes. CoRSIV methylation in one tissue can predict expression of associated genes in other tissues.

Conclusions: In addition to charting a previously unexplored molecular level of human individuality, this atlas of human CoRSIVs provides a resource for future population-based investigations into how interindividual epigenetic variation modulates risk of disease.
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http://dx.doi.org/10.1186/s13059-019-1708-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545702PMC
June 2019

Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes: a pooled analysis of prospective cohort studies.

Am J Clin Nutr 2019 04;109(4):1216-1223

Cardiovascular Health Research Unit.

Background: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed.

Objective: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies.

Methods: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants.

Results: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides.

Conclusions: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.
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http://dx.doi.org/10.1093/ajcn/nqz005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500926PMC
April 2019

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Circulation 2019 05;139(21):2422-2436

Benjamin Leon for Geriatrics Research and Education, Herbert Wertheim College of Medicine, Florida International University, Miami (P.H.M.C.).

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582360PMC
May 2019

The Need for Greater Rigor in Childhood Nutrition and Obesity Research.

JAMA Pediatr 2019 04;173(4):311-312

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington.

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http://dx.doi.org/10.1001/jamapediatrics.2019.0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259342PMC
April 2019

Spot Urine Sodium-to-Potassium Ratio Is a Predictor of Stroke.

Stroke 2019 02;50(2):321-327

Department of Epidemiology and Nutritional Sciences Program (A.D.), University of Washington, Seattle, WA.

Background and Purpose- Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods- The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results- Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07-2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions- The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.
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http://dx.doi.org/10.1161/STROKEAHA.118.023099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349502PMC
February 2019
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