Tanya L. Alderete, Ph.D.

OBJECTIVE Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery …

Although pediatric growth curves provide clinical utility, using these metrics for within‐person change over time can be misleading. As research is focused on understanding cardiometabolic consequences of weight gain, it is important to use precise metrics to analyze these longitudinal research questions. Despite several foundational recommendations to limit the use of reference pediatric growth curves (e.g., BMI z scores) for within‐person longitudinal research, it has evolved into the “gold standard” for using growth curves for pediatric weight gain analyses. Therefore, the objective of this paper is to discuss (A) the methodology used to create reference growth curves; (B) the appropriate use of reference pediatric BMI growth curves within the context of cross‐sectional and longitudinal analyses in research; and (C) how to select metrics based on desired evaluations. Careful consideration using standardized …

Introduction Shift work disorder (SWD) is a circadian rhythm sleep disorder associated with increased chance of experiencing poor mental health symptoms and physical health complaints. Traditional protective factors, such as resilience, as well as the ability to sleep at different times of the day, known as sleep flexibility, are known to reduce the risk of SWD, and to protect against poor mental health. However, more research is needed to understand how protective factors and SWD risk interact to predict health and wellbeing outcomes. The current study aimed to explore the role of traditional and sleep-specific protective factors in buffering the impact of high SWD risk on mental health and physical health complaints. Methods One hundred and twenty-six permanent nightshift workers or those working rotating shift schedules including nightshifts participated in an online cross …

BackgroundThe taxonomic composition of the gut microbiome undergoes rapid development during the first 2–3 y of life. Poor diet during complementary feeding has been associated with alterations in infant growth and compromised bone, immune system, and neurodevelopment, but how it may affect gut microbial composition is unknown.ObjectivesThis cross-sectional study aimed to examine the associations between early-life nutrition and the developing infant gut microbiota at 6 mo of age.MethodsLatino mother–infant pairs from the Mother’s Milk Study (n = 105) were included. Infant gut microbiota and dietary intake were analyzed at 6 mo of age using 16S ribosomal RNA amplicon sequencing and 24-h dietary recalls, respectively. Poisson generalized linear regression analysis was performed to examine associations between dietary nutrients and microbial community abundance while adjusting for infants …

BackgroundPer- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood.ObjectivesTo examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic).MethodsOverweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were …

Objective This study explores the impact of maternal pre‐pregnancy BMI on infant neurodevelopment at 24 months in low‐income Latino families. It also investigates whether infant diet mediates this relationship. Methods Latino mother‐infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6‐month intervals. Maternal pre‐pregnancy anthropometrics were self‐reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)‐2015 and HEI‐Toddlers‐2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations. Results Pre‐pregnancy BMI showed significant negative associations with child cognitive scores (β = −0.1, 95% CI: −0.2 to −0 …

IntroductionExposure to metals is associated with increased risk of type 2 diabetes (T2D). Potential mechanisms for metals-T2D associations involve biological processes including oxidative stress and disruption of insulin-regulated glucose uptake. In this study, we assessed whether associations between metal exposure and metabolite profiles relate to biological pathways linked to T2D.Materials and methodsWe used data from 29 adults rural Colorado residents enrolled in the San Luis Valley Diabetes Study. Urinary concentrations of arsenic, cadmium, cobalt, lead, manganese, and tungsten were measured. Metabolic effects were evaluated using untargeted metabolic profiling, which included 61,851 metabolite signals detected in serum. We evaluated cross-sectional associations between metals and metabolites present in at least 50% of samples. Primary analyses adjusted urinary heavy metal concentrations …

Background Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver. Objective The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies. Methods PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human …

BackgroundPer- and polyfluoroalkyl substances (PFAS) are pollutants linked to adverse health effects. Diet is an important source of PFAS exposure, yet it is unknown how diet impacts longitudinal PFAS levels.ObjectiveTo determine if dietary intake and food sources were associated with changes in blood PFAS concentrations among Hispanic young adults at risk of metabolic diseases.MethodsPredominantly Hispanic young adults from the Children’s Health Study who underwent two visits (CHS; n = 123) and young adults from NHANES 2013–2018 who underwent one visit (n = 604) were included. Dietary data at baseline was collected using two 24-hour dietary recalls to measure individual foods and where foods were prepared/consumed (home/restaurant/fast-food). PFAS were measured in blood at both visits in CHS and cross-sectionally in NHANES. In CHS, multiple linear regression assessed associations of …

To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 …

The assessment of “omics” signatures may contribute to personalized medicine and precision nutrition. However, the existing literature is still limited in the homogeneity of participants’ characteristics and in limited assessments of integrated omics layers. Our objective was to use post-prandial metabolomics and fasting proteomics to identify biological pathways and functions associated with diet quality in a population of primarily Hispanic young adults. We conducted protein and metabolite-wide association studies and functional pathway analyses to assess the relationships between a priori diet indices, Healthy Eating Index-2015 (HEI) and Dietary Approaches to Stop Hypertension (DASH) diets, and proteins (n = 346) and untargeted metabolites (n = 23,173), using data from the MetaAIR study (n = 154, 61% Hispanic). Analyses were performed for each diet quality index separately, adjusting for demographics and BMI. Five proteins (ACY1, ADH4, AGXT, GSTA1, F7) and six metabolites (undecylenic acid, betaine, hyodeoxycholic acid, stearidonic acid, iprovalicarb, pyracarbolid) were associated with both diets (p < 0.05), though none were significant after adjustment for multiple comparisons. Overlapping proteins are involved in lipid and amino acid metabolism and in hemostasis, while overlapping metabolites include amino acid derivatives, bile acids, fatty acids, and pesticides. Enriched biological pathways were involved in macronutrient metabolism, immune function, and oxidative stress. These findings in young Hispanic adults contribute to efforts to develop precision nutrition and medicine for diverse populations.

Human milk oligosaccharides (HMOs) impact neonate immunity and health outcomes. However, the environmental factors influencing HMO composition remain understudied. This study examined the associations between ambient air pollutant (AAP) exposure and HMOs at 1-month postpartum. Human milk samples were collected at 1-month postpartum (n = 185). AAP (PM2.5, PM10, NO2) exposure included the 9-month pregnancy period through 1-month postpartum. Associations between AAP with (1) HMO diversity, (2) the sum of sialylated and fucosylated HMOs, (3) 6 a priori HMOs linked with infant health, and (4) all HMOs were examined using multivariable linear regression and principal component analysis (PCA). Exposure to AAP was associated with lower HMO diversity. PM2.5 and PM10 exposure was positively associated with the HMO 3-fucosyllactose (3FL); PM2.5 exposure was positively …

Methods: MetaAir study participants (n= 154, 61% Hispanic) completed a clinical visit between 2014-2018. The Healthy Eating Index-2015, Dietary Approaches to Stop Hypertension, and Mediterranean diet scores were calculated from two 24-hour dietary recalls. Targeted proteomics (346 proteins) were measured in a cardiometabolic panel and untargeted metabolomics were assessed using LC-HRMS. The results of metabolite-and protein-wide association studies were used in functional pathway analysis with MetaboAnalyst and Reactome, respectively. Analyses were performed for each diet index separately, adjusting for demographics and BMI.Results: 16.4% of metabolite and 20% of protein features were significantly (p< 0.05) associated with at least one diet index. Two annotated metabolites (L-methionine, prostaglandin F2α) and four proteins (ACY1, ADH4, AGXT, GSTA1) were associated with all three dietary indices. These features are involved in amino acid metabolism, liver function, and inflammation, and are involved in biological pathways like arachidonic acid metabolism, prostaglandin formation, and biological oxidations. Overall, 21 metabolomics and 84 proteomics pathways were associated with at least one diet index and had similar functions, including those related to cell signaling and growth, hemostasis, immune function, and hormone regulation.Discussion: Adherence to healthy dietary patterns influences biological pathways involved in disease development and progression. Omics analyses may provide information about the mechanisms by which a healthy diet improves human health.

PurposeThe Cook Stove Pregnancy Cohort Study (CSPCS) was designed to assess the effects of biomass fuel use on household air pollution (HAP) as well as the effects of HAP (fine particulate matter, PM2.5) on birth outcomes and acute lower respiratory infection (ALRI) among infants in Bangladesh.ParticipantsWe recruited 903 women within 18 weeks of pregnancy from rural and semiurban areas of Bangladesh between November 2016 and March 2017. All women and their infants (N=831 pairs) were followed until 12 months after delivery and a subset have undergone respiratory and gut microbiota analysis.MethodsQuestionnaires were administered to collect detailed sociodemographic, medical, nutritional and behavioural information on the mother–child dyads. Anthropometric measurements and biological samples were also collected, as well as household PM2.5 concentrations.Findings to datePublished …

BackgroundExposure to ambient air pollution has been linked to asthma, allergic rhinitis, and other inflammatory disorders, but little is known about the underlying mechanisms.ObjectiveWe studied the potential mechanisms leading from prenatal ambient air pollution exposure to asthma and allergy in childhood.MethodsLong-term exposure to nitrogen dioxide (NO2) as well as to particulate matter with a diameter of ≤2.5 and ≤10 μm (PM2.5 and PM10) were modeled at the residence level from conception to 6 years of age in 700 Danish children followed clinically for development of asthma and allergy. Nasal mucosal immune mediators were assessed at age 4 weeks and 6 years, inflammatory markers in blood at 6 months, and nasal epithelial DNA methylation and gene expression at age 6 years.ResultsHigher prenatal air pollution exposure with NO2, PM2.5, and PM10 was associated with an altered nasal …

Purpose: The Cook Stove Pregnancy Cohort Study (CSPCS) was designed to assess the effects of biomass fuel use on household air pollution (HAP) as well as the effects of HAP (fine particulate matter, PM2.5) on birth outcomes and acute lower respiratory infection (ALRI) among infants in Bangladesh. Participants: We recruited 903 women within 18 weeks of pregnancy from rural and semiurban areas of Bangladesh between November 2016 and March 2017. All women and their infants (N=831 pairs) were followed until 12 months after delivery and a subset have undergone respiratory and gut microbiota analysis. Methods: Questionnaires were administered to collect detailed sociodemographic, medical, nutritional and behavioural information on the mother-child dyads. Anthropometric measurements and biological samples were also collected, as well as household PM2.5 concentrations. Findings to date …

Background and AimAmbient air pollution (AAP) exposure has been associated with altered blood lipids and liver fat in young adults. MicroRNAs regulate gene expression and may mediate these relationships. This work investigated associations between AAP exposure, serum microRNA networks, lipid profiles, and non-alcoholic fatty liver disease (NAFLD) risk in young adults.MethodsParticipants were 170 young adults (17–22 years) from the Meta-AIR cohort of the Children’s Health Study (CHS). Residential AAP exposure (PM2.5, PM10, NO2, 8-hour maximum O3, redox-weighted oxidative capacity [Oxwt]) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Fasting serum lipids were assayed. Liver fat was imaged by MRI and NAFLD was defined by ≥ 5.5% hepatic fat fraction. Serum microRNAs were measured via NanoString and microRNA networks were constructed by …

Background Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and has been associated with an increased risk of several cardiometabolic diseases. However, the metabolic pathways linking PFAS exposure and human disease are unclear. Objective We examined associations of PFAS mixtures with alterations in metabolic pathways in independent cohorts of adolescents and young adults. Methods Three hundred twelve overweight/obese adolescents from the Study of Latino Adolescents at Risk (SOLAR) and 137 young adults from the Southern California Children’s Health Study (CHS) were included in the analysis. Plasma PFAS and the metabolome were determined using liquid-chromatography/high-resolution mass spectrometry. A metabolome-wide association study was performed on log-transformed metabolites using Bayesian regression with a g-prior specification and g-computation for modeling …

BackgroundSocial determinants of health (SDoH) describe the complex network of circumstances that impact an individual before birth and across the lifespan. SDoH contextualize factors in a community that are associated with chronic disease risk and certain health disparities. The main objective of this study was to explore the impact of SDoH on the prevalence of obesity and diabetes, and whether these factors explain disparities in these health outcomes among Latinos in Southern California.MethodsWe utilized three composite indices that encompass different SDoH: the Healthy Places Index (HPI), Social Vulnerability Index (SVI), and CalEnviroScreen (CES). Univariate linear regression models explored the associations between index scores with adult obesity, adult diabetes, and childhood obesity.ResultsCommunities with lower HPI scores were associated with higher prevalence of metabolic disease and a …

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother’s Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may …