Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity

Insulin resistance (IR) affects a quarter of the world’s adult population and is a major factor in the pathogenesis of cardio-metabolic disease. In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from obese pre-diabetic Hispanic adolescents as indicators of abnormal metabolic regulation. Using the ReCIVA breathalyzer device for breath collection, we have identified a signature of 10 breath metabolites (breath-IR model), which correlates with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (R = 0.95, p < 0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R = 0.91, p < 0.001 and fasting glucose R = 0.80, p < 0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p = 0.003, p = 0.002, and p < 0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an AUC-ROC curve of 0.87, after cross-validation. Identification of a breath signature indicative of IR shows utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has potential as a diagnostic tool for monitoring IR progression, allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity

ABSTRACT Background: Insulin Resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. Non-invasive sampling of exhaled breath contains metabolic markers indicative of underlying systemic metabolic abnormality. Method: In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from pre-diabetic Hispanic adolescents with obesity as indicators of abnormal metabolic regulation. Findings: Exhaled breath collection using the ReCIVA breathalyzer is feasible in an adolescent population. We have identified a signature of breath metabolites (breath-IR model) which correlates with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R = 0.95, p <0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R=0.91, p <0.001 and fasting glucose R=0.80, p <0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p =0.003, p =0.002, and p<0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an area under the receiver operating characteristic curve of 0.87, after cross-validation. Interpretation: Identification of a breath metabolite signature indicative of IR in prediabetic Hispanic adolescents with obesity provides evidence of the utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has utility as a diagnostic tool for monitoring IR progression, potentially allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

PNPLA3 Genotype, Arachidonic Acid Intake, and Unsaturated Fat Intake Influences Liver Fibrosis in Hispanic Youth with Obesity

Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (β = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (βCC/CG = −0.0007, βGG = 0.03, p-value = 0.004), polyunsaturated fat (βCC/CG = −0.01, βGG = 0.02, p-value = 0.01), and omega-6 (βCC/CG = −0.0102, βGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.

Depressive Symptoms Among Hispanic Adolescents and Effect on Neonatal Outcomes

Introduction: Hispanics have the highest birth rate among adolescents and may be vulnerable to experience depression. The purpose of this study was to explore the prevalence of perinatal depression and effects upon neonatal outcomes among Hispanic adolescents 13–19 years old. Methods: Available data from a previously conducted study examining the prevalence of adolescent depression and post-traumatic stress were used for the current secondary analysis. Perinatal data reflected a rating of prenatal depression and scores from the Edinburgh Postpartum Depression Scale (EPDS). Adverse infant outcomes included preterm birth, low birth weight, and neonatal complications. Results: Over 20% of adolescents reported an adverse infant outcome. About one third of adolescents reported perinatal depression: prenatally (14%) and postnatally (14% minor depression/12.7% major depression). Significant associations were found between EPDS scores, gestational age, and feelings during pregnancy; however, perinatal depression was not found to predict adverse infant outcomes. Conclusion: Prenatally depressed adolescents are vulnerable to postpartum depression and if experience an adverse infant outcome, postpartum depression may be more likely reported. Therefore, prenatal- and afterbirth-focused assessments and care, including plans for follow-up, are essential.

Experienced, Anticipated, and Vicarious Discrimination: Consequences and Resilience for Minority Adolescents’ School Engagement

Racial discrimination presents challenges for children of color, particularly with regard to their schooling. Experiences of rejection and unfairness because of one’s race can prompt students to disengage from academics. The expansive discrimination literature finds that such experiences are commonplace. So much so that researchers have begun asking a new question: does one need to experience discrimination first-hand to feel its consequences? The current study continues in this direction by examining school attitudes as a potential outcome of anticipated and vicarious discrimination. Data are from black and Hispanic adolescents in the Project on Human Development in Chicago Neighborhoods. Results indicate that anticipated discrimination has the strongest and most direct associations with attitudes among African Americans, particularly when the police represent the discrimination source. However, parents can neutralize the impact of anticipated discrimination if they encourage reading at high levels. Experienced and vicarious discrimination exhibit weaker effects. Overall, the results confirm that the consequences of interpersonal discrimination do not stop with the intended victims. Instead, there are ripple effects that can negatively impact the worldviews of racial minority adolescents without them ever personally experiencing discrimination.