Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Skin Carotenoid Scores Are A Valid Approximation Of Fruit And Vegetable Intake Among Adults With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Elizabeth Gates, Melissa N Laska, Andrew R Dinardo, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third …

Dose-Expansion Study Of Obi-999, A Globo H-Targeting Antibody-Drug Conjugate, In Patients With Advanced Solid Tumors, Apostolia Maria Tsimberidou, Darren Sigal, Anna Varghese, Daniel Vaena, Li-Yuan Bai, Ming-Huang Chen, Chun-Nan Yeh, Chia-Jui Yen, Mehmet A Baysal, Abhijit Chakraborty, Ingly Lee, Chi-Sheng Shia, Konul Ristoski, Dong Xu

Children’s Nutrition Research Center Staff Publications

Background: OBI-999 is an antibody-drug conjugate consisting of the Globo H-targeting antibody OBI-888 linked to the cytotoxic payload monomethyl auristatin E. In a dose-escalation study, the OBI-999 recommended phase 2 dose (RP2D) was 1.2 mg/kg every 3 weeks. This dose-expansion study evaluated the efficacy and safety of OBI-999 in patients with pancreatic cancer, colorectal cancer (CRC), or other tumor types ("basket cohort") and tumoral Globo H H-scores ≥100 (NCT04084366).

Patients and methods: Patients were treated at RP2D of OBI-999. We assessed response, progression-free survival (PFS), treatment-emergent adverse events (TEAEs), and pharmacokinetics of OBI-999.

Results: Of 29 patients treated, …

All-Cause And Cause-Specific Mortality In Gambling Disorder: Evidence From A Nation-Wide Matched And Sibling Cohort Study In Taiwan, Yang-Chieh Brian Chen, Chih-Wei Hsu, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Background and aims: Gambling disorder (GD) has been linked to suicidal ideation and suicide deaths; however, evidence on all-cause and cause-specific mortality-particularly in Asian populations-remains limited. Using a retrospective cohort study based on nationwide matched and sibling cohort, we investigated all-cause and cause-specific mortality risk in patients with GD.

Design, setting and participants: A retrospective cohort study was conducted using 2000-2022 data from Taiwan's National Health Insurance Research Database. A cohort of 961 individuals diagnosed with GD was identified. An age- and sex-matched control cohort (n = 3,844) and an unaffected sibling cohort (n = 675) were constructed. Cumulative survival …

All-Cause And Cause-Specific Mortality In Patients With Bipolar Ii Disorder, Chih-Wei Hsu, Yang-Chieh Brian Chen, Edward Chia-Cheng Lai, Andrew A Nierenberg, Michael Berk, Sheng-Yu Lee, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I).

Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I.

Design, setting, and participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons …

A Case Of Autosomal Dominant Polycystic Kidney Disease With Multiple Bilateral Spontaneous Retroperitoneal Hemorrhages, Masato Mizuta, Tatsuya Suwabe, Yuki Oba, Akinari Sekine, Masayuki Yamanouchi, Hiroki Mizuno, Eiko Hasegawa, Takehiko Wada, Makoto Fukuda, Motoaki Miyazono, Naoki Sawa, Yoshifumi Ubara

Children’s Nutrition Research Center Staff Publications

We experienced a 45-year-old male with ADPKD who developed spontaneous retroperitoneal hemorrhages with hypertension in the right subcapsular renal space without trauma. After his condition worsened with conservative management, he was treated by renal transarterial embolization (TAE). Over the next eight years, he experienced bilateral bleeding at three different sites and underwent repeated endovascular treatment with renal TAE to stop the bleeding. After the fourth occurrence, the patient underwent hemodialysis. Although renal cysts and urinary tract bleeding occur frequently in ADPKD, retroperitoneal hemorrhage is rare; however, TAE is both effective and a good way to preserve renal function.

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …

Perceptions And Use Of Behaviour Change Interventions For Physical Activity In Chronic Respiratory Disease In The Republic Of Ireland, Ciara Hanrahan, Joseph G Mcveigh, Terence M O'Connor, Thierry Troosters, Julie Broderick

Children’s Nutrition Research Center Staff Publications

Objectives: Behaviour change interventions may support physical activity behaviour in people with chronic respiratory disease. The most effective interventions for long-term physical activity behaviour change in this cohort remains unclear. This aim of this study was to explore the use and perceptions of behaviour change interventions by both providers of physical activity programmes for people with chronic respiratory disease and by people living with chronic obstructive pulmonary disease (COPD) in The Republic of Ireland.

Design: Two anonymous online and paper-copy cross-sectional surveys, piloted and mapped to the COM-B model of behaviour change, were distributed via social media and relevant gate-keepers …

Catatonia And Elevated Mortality: A Population-Wide Cohort Study With Healthy, Sibling, And Schizophrenia Spectrum Controls, Chih-Wei Hsu, Yang-Chieh Brian Chen, Marco Solmi, Chih-Sung Liang, Mu-Hong Chen, Yao-Hsu Yang, Liang-Jen Wang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aim: To determine whether catatonia is associated with increased long-term all-cause and cause-specific mortality.

Methods: Using Taiwan's National Health Insurance Database (2000-2022), we assembled a population-based cohort of all adults (≥18 years) with catatonia and matched each to four controls without catatonia on sex and birthdate. Mortality was compared between (1) individuals with catatonia and their unaffected siblings and (2) individuals with schizophrenia spectrum disorders with catatonia and those with schizophrenia spectrum disorders without catatonia. The primary outcome was all-cause mortality; secondary outcomes were natural- and unnatural-cause deaths. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with …

Uncovering Predictors Of Bipolar Ii Conversion To Bipolar I: A Machine Learning Analysis Of National Health Records In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Kuo-Chuan Hung, Mu-Hong Chen, Eduard Vieta, Chien-Yuan Chen, Chih-Sung Liang, Andre F Carvalho

Children’s Nutrition Research Center Staff Publications

Background: Bipolar II disorder (BD-II) can progress to bipolar I disorder (BD-I), carrying profound psychosocial consequences. However, limited research has investigated the transition from BD-II to BD-I. Our study uses machine learning to predict the conversion using real-world data.

Methods: We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database (2000-2013) to identify adults diagnosed with BD-II. A predictive model for BD-I conversion was developed using extreme gradient boosting (XGBoost), incorporating demographic factors, healthcare utilization, comorbidities, and psychotropic medication use. The dataset was randomly divided into development (80 %) and test (20 %) sets. Model performance …

N-Palmitoyl Glutamine Is A Candidate Mediator Of Cardiorespiratory Fitness, Jeremy M Robbins, Mark Benson, Anthony R P Verkerke, Gaurav Tiwari, Shuliang Deng, Prashant Rao, Usman A Tahir, Julian Avila-Pacheco, Xu Shi, Yuntian Guan, Foje-Geh Tendoh, Jacob L Barber, Patricia E Miller, Andrew S Perry, Michael E Hall, Alexis C Wood, Kent D Taylor, Wendy S Post, Stephen S Rich, Matthew Nayor, James G Wilson, Gregory D Lewis, Ravi V Shah, Jerome I Rotter, Scott A Summers, Laura M Raffield, Shingo Kajimura, Claude Bouchard, Clary B Clish, Mark A Sarzynski, Robert E Gerszten

Children’s Nutrition Research Center Staff Publications

Background: Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Methods: We performed nontargeted liquid chromatography mass spectrometry-based plasma metabolomics in 654 participants (mean age, 35 years; 55% women) from the HERITAGE Family Study (Health, Risk Factors, Exercise Training, and Genetics) who had cardiorespiratory fitness (maximal oxygen uptake [VO2max]) measured by cardiopulmonary exercise testing and underwent 20 weeks of supervised endurance training. Metabolite-VO2max relationships were assessed using linear regression …

Insulinemic And Inflammatory Dietary Patterns And Colorectal Cancer Risk: A Dietary Data Harmonization Study Of One Million Participants In The Consortium Of Metabolomics Studies (Comets), Ni Shi, Rachel Hoobler, Rhea Harewood, Amanda E Toland, Demetrius Albanes, Emmanouil Bouras, Marc J Gunter, Linda M Liao, Steven C Moore, Fulvio Ricceri, Jerome I Rotter, Rashmi Sinha, Rachael Stolzenberg-Solomon, Anne Tjønneland, Alexis C Wood, Danxia Yu, Mary C Playdon, Fred K Tabung

Children’s Nutrition Research Center Staff Publications

Background: Inflammatory and insulinemic dietary patterns have been associated with colorectal cancer (CRC) risk, but generalizability across diverse populations with heterogeneous food supplies and dietary behaviors has not been established.

Objectives: We harmonized disparate dietary and covariate data on a large scale to compute the reverse Empirical Dietary Index for Hyperinsulinemia (rEDIH), reverse Empirical Dietary Inflammatory Pattern (rEDIP), and Healthy Eating Index (HEI)-2015 scores, and tested their associations with CRC risk.

Methods: We leveraged data among 501,892 women and 407,390 men from 6 cohorts across the United States (NIH-AARP, Multi-Ethnic Study of Atherosclerosis, Prostate, Lung, Colorectal, and Ovarian, SCCS) and …

“Shaking The Ladder” Reveals How Analytic Choices Can Influence Associations In Nutrition Epidemiology: Beef Intake And Coronary Heart Disease As A Case Study, Colby J Vorland, Lauren E O'Connor, Beate Henschel, Cuiqiong Huo, James M Shikany, Carlos A Serrano, Robert Henschel, Stephanie L Dickinson, Keisuke Ejima, Aurelian Bidulescu, David B Allison, Andrew W Brown

Children’s Nutrition Research Center Staff Publications

Nutrition epidemiological models involve many analytic decisions, such as defining exposures, selecting which covariates to include, or configuring variables in different ways. We explored the impact of analytical decisions on conclusions in nutrition epidemiology using self-reported beef intake and incident coronary heart disease as a case study. We used REasons for Geographic and Racial Differences in Stroke (REGARDS) data, and selected covariates and their configurations from published literature to recapitulate common models used to assess associations between meat intake and health outcomes. Three model sets were designed: sets one and two used continuous and quintile-defined beef intakes, respectively, each with …

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

Dna Methylation Markers Of Insulin Resistance Surrogate Measures In The Atherosclerosis Risk In Communities (Aric) Study, Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski

Faculty, Staff and Student Publications

Insulin resistance (IR) is a risk factor for cardiovascular diseases and type 2 diabetes. Associations between DNA methylation (DNAm) and IR have been less studied in African ancestry (AA) populations than those of European ancestry (EA). We aimed to identify associations between whole blood DNAm and IR in up to 1,811 AA and 964 EA participants from the Atherosclerosis Risk in Communities (ARIC) study. We quantified IR using three surrogate measures: the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose index (TyG), and the triglyceride glucose-body mass index (TyG-BMI). We used ancestry-stratified linear regression models to conduct epigenome-wide association …

All-Cause And Cause-Specific Mortality Among Patients With Narcolepsy., Chih-Wei Hsu, Yen-Shan Yang, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Importance: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

Objective: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

Design, setting, and participants: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 …

Menopause Factors And Alterations In Gut Microbiota And Insulin Homeostasis: A Cross-Sectional Analysis Of The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Vincent J Maffei, Alain G Bertoni, Alexis C Wood, Jerome I Rotter, Osa Crago, Yii-Der I Chen, Joseph F Petrosino, Kristi L Hoffman, Mark O Goodarzi, Elizabeth T Jensen

Children’s Nutrition Research Center Staff Publications

Aim: To assess the risk for impaired insulin homeostasis as a function of menopause-related factors and gut microbiota dysbiosis in non-diabetic, post-menopausal women.

Materials and methods: Baseline data (n = 175 women) from the Microbiome and Insulin Longitudinal Evaluation Study (MILES) were used, including insulin and dysglycaemia indices calculated from a 2-h oral glucose tolerance test, untargeted peripheral metabolomics, targeted peripheral short chain fatty-acid levels and faecal bacterial microbiota surveyed by whole-metagenomic sequencing.

Results: After adjustment for covariates, menopause age < 50 years and use of hormone replacement therapy (HRT) were associated with lower Matsuda et al. insulin sensitivity index levels (β = -0.232, confidence interval (CI) = [-0.450, -0.014] and β = -0.275, CI = [-0.444, -0.107], respectively) but not pre-menopausal gynaecologic surgery. Pre-menopausal gynaecologic surgery was significantly associated with faecal microbiota beta diversity driven by a relative increase in diabetogenic Ruminococcus gnavus and Clostridium species and a decrease in protective Alistipes species and Akkermansia muciniphila relative abundances. A reduction in two glycerophospholipids in the plasmalogen class significantly statistically mediated an inverse association between gynaecologic surgery before menopause and insulin sensitivity.

Conclusions: Menopause age and history of HRT are more strongly associated with insulin resistance than gynaecologic surgery before menopause. However, …

Amino Acids And Cart Distinguish A-Β+ Ketosis-Prone Diabetes From Type 1 And Type 2 Diabetes During Hyperglycemic Crises, Farook Jahoor, Jean W Hsu, Kelly R Keene, W Frank Peacock, Xiaofang Huang, Danielle Guffey, Jinyoung Byun, Rasmus Bennet, Ake Lernmark, Mustafa Tosur, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Context: When clinically stable, patients with A-β+ ketosis-prone diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D, and T2D patients during hyperglycemic crises, and utilize classification and regression tree (CART) modeling to distinguish these forms of diabetes.

Methods: At an urban hospital emergency center, adults with KPD, T1D, and T2D during hyperglycemic crises with or without diabetic ketoacidosis (DKA), and healthy controls, underwent comparisons of serum metabolite and hormonal profiles and CART analyses. …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

Patient-Centered, Theory-Based, Online Intervention To Promote A Physically Active Lifestyle For People With Multiple Sclerosis: Protocol For A Randomized Controlled Trial, Chungyi Chiu, Vaishnavi Sridharan, Mojtaba Khaliji, Md Refat Uz Zaman Sajib, Xiaotian Gao, Kathleen Zackowski

Children’s Nutrition Research Center Staff Publications

Background: People with multiple sclerosis (MS) experience life challenges due to the nature of disease progression. Although an active lifestyle has been shown effective for symptom and relapse management, most people with MS lead a sedentary lifestyle and do not reach the recommended physical activity (PA) guidelines.

Objective: This study aims to test the preliminary efficacy of a codeveloped, online self-management intervention based on the health action process approach (HAPA) adapted for people with MS to cultivate a physically active lifestyle.

Methods: The 8-week intervention program was developed using community-based participatory research based on the HAPA. The program includes increasing …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

The Overlooked Impact Of Background Diet And Adherence In Nutrition Trials, Javier I Ottaviani, Hagen Schroeter, Dennis M Bier, John W Erdman, Howard D Sesso, Joann E Manson, Gunter G C Kuhnle

Children’s Nutrition Research Center Staff Publications

Randomised controlled trials in nutrition (RCTN) face unique challenges, including the considerable influence of the background diet and the challenge of assuring intervention adherence by participants. The impact of these factors on the outcome of RCTNs has been difficult to quantify, but nutritional biomarkers represent a valuable tool to address these challenges. Using flavanols as a model dietary intervention and a set of recently validated flavanol biomarkers, we here investigated the impact of background diet and adherence on the outcomes of a subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS, NCT 02422745). We found that 20% of participants …

Defining Lipedema’S Molecular Hallmarks By Multi-Omics Approach For Disease Prediction In Women, Leon G Straub, Jan-Bernd Funcke, Nolwenn Joffin, Chanmin Joung, Sara Al-Ghadban, Shangang Zhao, Qingzhang Zhu, Ilja L Kruglikov, Yi Zhu, Paul R Langlais, Ruth Gordillo, Karen L Herbst, Philipp E Scherer

Children’s Nutrition Research Center Staff Publications

Lipedema is a chronic disease in females characterized by pathologic subcutaneous adipose tissue expansion and hitherto remains without druggable targets. In this observational study, we investigated the molecular hallmarks of lipedema using an unbiased multi-omics approach. We found adipokine dysregulation in lipedema patients participating in a cross-sectional clinical study (ClinicalTrial.gov, NCT02838277), pointing towards the adipocyte as a key player. Analyses of newly generated transcriptomic (SRA, PRJNA940039) and proteomic (ProteomeXchange, PXD058489) datasets of early- and late-stage lipedema samples revealed a local downregulation of factors involved in inflammation. Concomitantly, factors involved in cellular respiration, oxidative phosphorylation, as well as in mitochondrial …

Time To Weight Plateau With Tirzepatide Treatment In The Surmount-1 And Surmount-4 Clinical Trials, Deborah B Horn, Scott Kahan, Rachel L Batterham, Dachuang Cao, Clare J Lee, Madhumita Murphy, Sylvia Gonsahn-Bollie, Farai Chigutsa, Adam Stefanski, Julia P Dunn

Faculty, Staff and Student Publications

The rate of weight reduction during obesity treatment declines over time and eventually reaches a weight plateau. We investigated factors associated with time to weight plateau (TTWP) in tirzepatide-treated participants with obesity or overweight in a post-hoc analysis of SURMOUNT-1 and SURMOUNT-4 trials. Participants adherent to tirzepatide treatment and achieving ≥5% weight loss by primary endpoint (week 72 SURMOUNT-1; week 88 SURMOUNT-4) were included. Weight plateau was defined as a weight change < 5% over a 12-week interval and all subsequent 12-week intervals. TTWP was time from randomization to the start of the first 12-week interval. Association between baseline characteristics and TTWP was assessed. Overall, 1438 participants in SURMOUNT-1 and 259 in SURMOUNT-4 were included. Across BMI categories (overweight, class I, II, and III), median TTWP in SURMOUNT-1 was 24.3, 26.0, 36.1, and 36.1 weeks, respectively (p < .05, class II and III vs. overweight). By week 72, 90.2%, 88.9%, 87.6%, and 87.8% of participants in SURMOUNT-1 had reached a weight plateau across respective BMI categories [Correction added on 22 January 2025, after first online publication: The "72%" has been changed to "72" in this version.]. Higher doses of tirzepatide (10/15 mg), younger age, and female sex were more likely to reach a weight plateau later. Results in SURMOUNT-4 were similar. In this post-hoc analysis, most participants reached a weight plateau by week 72. Higher doses of tirzepatide, younger age, and female sex were associated with a longer TTWP. Further research into modifiers of weight reduction phases with tirzepatide may inform treatment decisions for its use in chronic weight management. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT04184622 (SURMOUNT-1) and NCT04660643 (SURMOUNT-4), available at http://www.clinicaltrials.gov/.

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

Adipose Progenitor Cell-Derived Extracellular Vesicles Suppress Macrophage M1 Program To Alleviate Midlife Obesity, Qing Zhou, Jia Gao, Guorao Wu, Chenwei Wang, Yan Yang, Teng Huang, Yi Wang, Tiantian Yue, Zhichao Gao, Hao Xie, Fei Xiong, Ke Xiang, Tuying Yong, Wanguang Zhang, Tongtong Zhang, Wen Kong, Cai Chen, Shu Zhang, Qilin Yu, Xuemei Fan, Shiwei Liu, Yanjun Liu, Cong-Yi Wang

Children’s Nutrition Research Center Staff Publications

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs …

Exploring Profiles Of Fathers Integrating Food And Physical Activity Parenting Practices, John A Jimenez-Garcia, Louise C Mâsse, Robert L Newton, Salma M Musaad, Alicia Beltran, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Objective: This study aims to identify fathers' profiles integrating food parenting practices (FPP) and physical activity parenting practices (PAPP).

Design: We analysed cross-sectional data. The fathers completed the reduced FPP and PAPP item banks and socio-demographic and family dynamics (co-parenting and household responsibility) questionnaires. We identified fathers' profiles via latent profile analysis. We explored the influence of social determinants, child characteristics and family dynamics on fathers' profiles using multinomial logistic regression.

Setting: Online survey in the USA.

Participants: Fathers of 5-11-year-old children.

Results: We analysed data from 606 fathers (age = 38 ± 8·0; Hispanic = 37·5 %). Most fathers …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

A Reflection-Spectroscopy Measured Skin Carotenoid Score Strongly Correlates With Plasma Concentrations Of All Major Dietary Carotenoid Species Except For Lycopene, Qiang Wu, Cheryl Webb Cherry, Stephanie Jilcott Pitts, Melissa N Laska, Neal Craft, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoids can be measured non-invasively using spectroscopy methods to provide a biomarker of total dietary carotenoid and carotenoid-rich fruit and vegetable intake. However, the degree to which skin carotenoid biomarkers reflect intakes of specific carotenoids must be determined for specific devices. Previously, findings were mixed regarding the correlation between reflection spectroscopy (RS)-assessed skin carotenoids and individual plasma carotenoid concentrations. The current study expands on prior analyses to examine the cross-sectional associations between adult RS-assessed skin carotenoids and individual carotenoid species intakes and plasma concentrations, controlling for potential covariates. We hypothesized that RS-assessed skin carotenoid scores would strongly correlate with …

Untargeted Metabolome Atlas For Sleep-Related Phenotypes In The Hispanic Community Health Study/Study Of Latinos, Ying Zhang, Brian W Spitzer, Yu Zhang, Danielle A Wallace, Bing Yu, Qibin Qi, Maria Argos, M Larissa Avilés-Santa, Eric Boerwinkle, Martha L Daviglus, Robert Kaplan, Jianwen Cai, Susan Redline, Tamar Sofer

Faculty, Staff and Student Publications

BACKGROUND: Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep-related phenotypes and blood metabolites.

METHODS: Utilising data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep-related phenotypes, grouped in several domains (sleep disordered breathing (SDB), sleep duration, sleep timing, self-reported insomnia symptoms, excessive daytime sleepiness (EDS), and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualise and interpret the associations between sleep phenotypes …