ABSTRACT
Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated "omic" fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.
Subject(s)
American Heart Association , Cardiovascular Diseases , Child , Adolescent , Humans , Risk Factors , Obesity/complications , Biomarkers , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & controlABSTRACT
Cardiorespiratory fitness (CRF) refers to the capacity of the circulatory and respiratory systems to supply oxygen to skeletal muscle mitochondria for energy production needed during physical activity. CRF is an important marker of physical and mental health and academic achievement in youth. However, only 40% of US youth are currently believed to have healthy CRF. In this statement, we review the physiological principles that determine CRF, the tools that are available to assess CRF, the modifiable and nonmodifiable factors influencing CRF, the association of CRF with markers of health in otherwise healthy youth, and the temporal trends in CRF both in the United States and internationally. Development of a cost-effective CRF measurement process that could readily be incorporated into office visits and in field settings to screen all youth periodically could help identify those at increased risk.
Subject(s)
American Heart Association , Cardiorespiratory Fitness , Exercise , Mental Health , Adolescent , Humans , United StatesABSTRACT
This scientific statement presents considerations for clinical management regarding the assessment and risk reduction of select pediatric populations at high risk for premature cardiovascular disease, including acquired arteriosclerosis or atherosclerosis. For each topic, the evidence for accelerated acquired coronary artery disease and stroke in childhood and adolescence and the evidence for benefit of interventions in youth will be reviewed. Children and adolescents may be at higher risk for cardiovascular disease because of significant atherosclerotic or arteriosclerotic risk factors, high-risk conditions that promote atherosclerosis, or coronary artery or other cardiac or vascular abnormalities that make the individual more vulnerable to the adverse effects of traditional cardiovascular risk factors. Existing scientific statements and guidelines will be referenced when applicable, and suggestions for risk identification and reduction specific to each setting will be described. This statement is directed toward pediatric cardiologists, primary care providers, and subspecialists who provide clinical care for these young patients. The focus will be on management and justification for management, minimizing information on pathophysiology and epidemiology.
Subject(s)
Atherosclerosis , Coronary Artery Disease , Adolescent , American Heart Association , Atherosclerosis/diagnosis , Atherosclerosis/therapy , Child , Child, Preschool , Coronary Artery Disease/diagnosis , Coronary Artery Disease/therapy , Female , Humans , Infant , Male , Practice Guidelines as Topic , Risk Factors , United StatesABSTRACT
Asthma in the obese is often severe, difficult to treat, and characterized by less eosinophilic inflammation than asthma in the nonobese. Obesity-associated metabolic dysregulation may be a causal factor. We previously reported that a nutrient- and fiber-dense bar [Children's Hospital Oakland Research Institute (CHORI)-bar], which was designed to fill gaps in poor diets, improved metabolism in healthy overweight/obese (OW/OB) adults. In this pilot trial, OW/OB adolescents with poorly controlled asthma were randomized to weekly nutrition/exercise classes with or without twice-daily CHORI-bar consumption. Intent-to-treat analysis did not indicate CHORI-bar-specific effects. However, restricting the analysis to participants with acceptable compliance and a relatively low fraction of exhaled nitric oxide (FENO; <50/ ppb, a surrogate for noneosinophilic asthma; study participants: CHORI-bar, n = 16; controls, n = 15) indicated that CHORI-bar-specific, significant improvements in lung function (forced vital capacity, percent-predicted forced expiratory volume in 1 s, and percent-predicted forced expiratory flow between 25 and 75% of forced vital capacity), primarily in participants with low chronic inflammation (high-sensitivity C-reactive protein <1.5 mg/L). (We previously observed that chronic inflammation blunted CHORI-bar-induced metabolic improvements in healthy OW/OB adults.) Lung function improvement occurred without weight loss and was independent of improvements in metabolic and anthropometric end points and questionnaire-based measures of asthma control and quality of life. This study suggests that a nutritional intervention can improve lung function in OW/OB adolescents with asthma and relatively low FENO without requiring major changes in dietary habits, lifestyle, or weight loss and that this effect is blunted by chronic inflammation.-Bseikri, M., McCann, J. C., Lal, A., Fong, E., Graves, K., Goldrich, A., Block, D., Gildengoren, G. L., Mietus-Snyder, M., Shigenaga, M., Suh, J., Hardy, K., Ames, B. N. A novel nutritional intervention improves lung function in overweight/obese adolescents with poorly controlled asthma: the Supplemental Nutrition in Asthma Control (SNAC) pilot study.
ABSTRACT
PURPOSE AND OBJECTIVES: The objective of our study was to strengthen wellness policy in Title 1 schools by implementing a mentored behavior-change model that extends the continuum of care from academic to community settings and mobilizes existing public resources in accordance with US Preventive Services Task Force screening guidelines for childhood obesity management. INTERVENTION APPROACH: Team Kid POWER! (KiPOW!) health mentors (students and trainees in medical and health-related fields) in 2 geographically and demographically distinct school districts, the District of Columbia and Orange County, California, delivered standardized health curricular modules to fifth grade classrooms, modeled healthy eating behaviors during school lunchtime, and engaged in active play at recess. EVALUATION METHODS: Initial interventions in the the District of Columbia and Orange County delivered 10 sessions in which all participants received the intervention. Two subsequent interventions in Orange County, for 5 weeks (Lite) and 10 weeks (Full), included controls. Pre-post measurements of body mass index (BMI) and blood pressure were documented in all participants. A mixed linear regression model, which included a random effect for each school, estimated differences between Full and Lite interventions compared with controls, adjusting for site, sex, and baseline status of the dependent variable. RESULTS: KiPOW! Full, but not KiPOW! Lite, was associated with a modest reduction in BMI percentile compared with control (KiPOW! Full, P = .04; KiPOW! Lite, P = .41), especially in Orange County (P < .001). Systolic blood pressure improved in Full (P < .046) more than in Lite interventions (P = .11), and diastolic blood pressure improved in both Full (P = .02) and Lite (P = .03) interventions. Annual renewal of the school and volunteer commitment needed to maintain KiPOW! was found to be sustainable. IMPLICATIONS FOR PUBLIC HEALTH: KiPOW! is a generalizable academic-community partnership promoting face-to-face contact between students and trusted health mentors to reinforce school wellness policies and foster youth confidence in decision-making about nutrition- and activity-related behaviors to achieve reduced BMI percentile and lowered blood pressure.
Subject(s)
Health Policy , Health Promotion/organization & administration , Mentors , Pediatric Obesity/therapy , School Health Services , California , Child , Diet, Healthy , District of Columbia , Female , Health Behavior , Humans , Male , StudentsABSTRACT
Objectives: Evidence in adults suggests that improvements in cognitive performance may follow weight loss resulting from bariatric surgery, and baseline cognitive performance may be associated with weight loss following surgery. This has not been evaluated in adolescents. Method: Participants were 38 adolescents of age 14-21 years composed of three groups: (1) 12 adolescents with severe obesity who received vertical sleeve gastrectomy during the study (VSG); (2) 14 adolescents with severe obesity who were wait-listed for VSG (WL); and (3) 12 healthy weight controls (HC). Participants completed testing of visual memory, verbal memory, and executive functioning at baseline (T1), which occurred presurgery for the VSG group, and approximately 4 months after baseline (T2). Body mass index (BMI) was assessed at T1, T2, and additionally at 6 months following VSG for the adolescents who received surgery. Results: Although there was evidence of greater improvement for the VSG as compared with WL and HC groups in visual and verbal memory, group differences did not reach significance and effect sizes were small (η2 < 0.01). There was a significant positive association between indices of baseline executive functioning and excess BMI loss at 6 months postsurgery. Conclusions: This small pilot study showed no significant differences by group in cognitive performance post-VSG. There was a significant association of baseline cognitive performance with weight loss outcomes. Given the very preliminary nature of these results in a small sample, future research should examine these relationships in a larger sample and evaluate mechanisms of these associations (e.g., insulin resistance, sleep, physical activity).
Subject(s)
Bariatric Surgery , Cognition/physiology , Obesity, Morbid/surgery , Adolescent , Adult , Body Mass Index , Female , Humans , Male , Obesity, Morbid/psychology , Pilot Projects , Postoperative Period , Treatment Outcome , Weight Loss , Young AdultABSTRACT
This study determined if twice-daily consumption of a nutrient-dense bar intended to fill gaps in Western diets, without other dietary/lifestyle requirements, favorably shifted metabolic/anthropometric indicators of dysregulation in a healthy direction. Three 8-wk clinical trials in 43 healthy lean and overweight/obese (OW/OB) adults, who served as their own controls, were pooled for analysis. In less inflamed OW/OB [high-sensitivity C-reactive protein (hsCRP) <1.5], statistically significant decreases occurred in weight (-1.1 ± 0.5 kg), waist circumference (-3.1 ± 1.4 cm), diastolic blood pressure (-4.1 ± 1.6 mmHg), heart rate [HR; -4.0 ± 1.7 beats per minute (bpm)], triglycerides (-72 ± 38.2 mg/dl), insulin resistance (homeostatic model of insulin resistance) (-0.72 ± 0.3), and insulin (-2.8 ± 1.3 mU/L); an increase in HDL-2b (+303 ± 116 nM) and realignment of LDL lipid subfractions toward a less atherogenic profile [decreased small LDL IIIb (-44 ± 23.5 nM), LDL IIIa (-99 ± 43.7 nM), and increased large LDL I (+66 ± 28.0 nM)]. In the more inflamed OW/OB (hsCRP >1.5), inflammation was reduced at 2 wk (-0.66 mg/L), and HR at 8 wk (-3.4 ± 1.3 bpm). The large HDL subfraction (10.5-14.5 nm) increased at 8 wk (+346 ± 126 nM). Metabolic improvements were also observed in lean participants. Thus, favorable changes in measures of cardiovascular health, insulin resistance, inflammation, and obesity were initiated within 8 wk in the OW/OB by replacing deficiencies in Western diets without requiring other dietary or lifestyle modifications; chronic inflammation blunted most improvements.
Subject(s)
Dyslipidemias/physiopathology , Inflammation/physiopathology , Insulin Resistance/physiology , Obesity/physiopathology , Overweight/physiopathology , Weight Loss/physiology , Adult , Blood Glucose/metabolism , Blood Pressure/physiology , Body Mass Index , C-Reactive Protein/metabolism , Cardiovascular System/metabolism , Cardiovascular System/physiopathology , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Dyslipidemias/metabolism , Female , Food , Heart Rate/physiology , Humans , Inflammation/metabolism , Insulin/metabolism , Male , Middle Aged , Obesity/metabolism , Overweight/metabolism , Triglycerides/metabolismABSTRACT
INTRODUCTION: Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents. METHODS: We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. We used logistic regression to examine the relationship between household food security status and the odds of having abnormalities with fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, and apolipoprotein B (Apo B). Models included age, sex, race/ethnicity, smoking status, partnered status in the household, and maternal education, with additional adjustment for adiposity. RESULTS: Household food security status was not associated with elevated TC or LDL-C. Adolescents with marginal food security were more likely than food-secure peers to have elevated TGs (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.14-3.05), TG/HDL-C ratio (OR = 1.74; 95% CI, 1.11-2.82), and Apo B (OR = 1.98; 95% CI, 1.17-3.36). Female adolescents with marginal food security had greater odds than male adolescents of having low HDL-C (OR = 2.69; 95% CI, 1.14-6.37). No elevated odds of dyslipidemia were found for adolescents with low or very low food security. Adjustment for adiposity did not attenuate estimates. CONCLUSION: In this nationally representative sample, low-income adolescents living in households with marginal food security had increased odds of having a pattern consistent with atherogenic dyslipidemia, which represents a cardiometabolic burden above their risk from adiposity alone.
Subject(s)
Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dyslipidemias/epidemiology , Food Supply/statistics & numerical data , Triglycerides/blood , Adolescent , Apolipoproteins B/blood , Child , Female , Humans , Logistic Models , Male , Nutrition Surveys , Odds Ratio , Poverty , Risk Factors , Self Report , United StatesABSTRACT
OBJECTIVE: To examine whether longitudinal changes in relative weight category (as indicated by change in body mass index [BMI] classification group) were associated with changes in nuclear magnetic resonance (NMR)-derived lipoprotein particles among US youth. STUDY DESIGN: Secondary analysis of data from a clustered randomized controlled trial. BMI and fasting blood samples were obtained from 2069 participants at the start of the 6th grade and end of the 8th grade. BMI was categorized as normal weight, overweight, or obese at both time points. Lipoprotein particle profiles were measured with NMR spectroscopy at both time points. Regression models were used to examine changes in relative weight group and change in lipoprotein variables. RESULTS: A total of 38% of participants changed relative weight category (BMI group) during the 2.5-year study period. Low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (HDL) cholesterol decreased almost universally, but more with improved BMI category. There were adverse effects on LDL size and total LDL particles, HDL size, and cholesterol for participants who remained obese or whose relative weight group worsened. Changes in relative category had no impact on HDL particles. CONCLUSION: Improvement in relative weight group from 6th to 8th grade was associated with favorable changes in non-HDL cholesterol, very low-density lipoprotein size, LDL size, HDL size, and LDL particles but had no effect on HDL particles. Findings indicate that an improvement in relative weight group between 6th and 8th grade had an effect on NMR-derived particles sizes and concentrations among a large group of adolescents, which overrepresented low-income minorities.
Subject(s)
Cholesterol, HDL/chemistry , Cholesterol, LDL/chemistry , Cholesterol, VLDL/chemistry , Particle Size , Pediatric Obesity/blood , Weight Gain , Weight Loss , Adolescent , Biomarkers/blood , Biomarkers/chemistry , Body Mass Index , Child , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cholesterol, VLDL/blood , Female , Follow-Up Studies , Humans , Linear Models , Magnetic Resonance Spectroscopy , Male , Overweight/blood , Thinness/bloodABSTRACT
OBJECTIVES: To characterize lipids and lipoproteins in a diverse school-based cohort and identify features associated with discordance between low-density lipoprotein cholesterol (LDL-C) and LDL particle (LDL-P). STUDY DESIGN: Sixth-grade children enrolled in the HEALTHY trial (n = 2384; mean age 11.3 ± 0.6 years; 54.2% female) were evaluated for standard lipids, lipoprotein particles measured by nuclear magnetic resonance, and homeostatic model of insulin resistance. Characteristics of subgroups with values of LDL-C and LDL-P discordant by >20 percentile units, an amount reasoned to be clinically significant, were compared. RESULTS: Four-hundred twenty-eight (18%) of children were in the LDL-P < LDL-C subgroup and 375 (16%) in the LDL-P > LDL-C subgroup. Those with LDL-P > LDL-C had significantly greater body mass index, waist circumference, homeostatic model of insulin resistance, triglycerides, systolic and diastolic blood pressure, and reflected a greater Hispanic ethnic composition but fewer of black race than both the concordant (LDL-P â LDL-C) and opposite discordant (LDL-P < LDL-C) subgroups. CONCLUSIONS: There is as much lipoprotein cholesterol compositional heterogeneity in sixth graders as has been described in adults and a discordant atherogenic phenotype of LDL-P > LDL-C, common in obesity, is often missed when only LDL-C is considered. Conversely, many children with moderate-risk cholesterol measures (75th to 99th percentile) have a lower LDL-P burden.
Subject(s)
Cholesterol, LDL/blood , Lipoproteins, LDL/blood , Child , Female , Humans , Male , Particle SizeABSTRACT
Dietary intake modulates disease risk, but little is known how components within food mixtures affect pathophysiology. A low-calorie, high-fiber, fruit-based nutrient-dense bar of defined composition (e.g., vitamins and minerals, fruit polyphenolics, ß-glucan, docosahexaenoic acid) appropriate for deconstruction and mechanistic studies is described and evaluated in a pilot trial. The bar was developed in collaboration with the U.S. Department of Agriculture. Changes in cardiovascular disease and diabetes risk biomarkers were measured after 2 wk twice-daily consumption of the bar, and compared against baseline controls in 25 healthy adults. Plasma HDL-cholesterol (HDL-c) increased 6.2% (P=0.001), due primarily to a 28% increase in large HDL (HDL-L; P<0.0001). Total plasma homocysteine (Hcy) decreased 19% (P=0.017), and glutathione (GSH) increased 20% (P=0.011). The changes in HDL and Hcy are in the direction associated with decreased risk of cardiovascular disease and cognitive decline; increased GSH reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed. A defined food-based supplement can, within 2 wk, positively impact metabolic biomarkers linked to disease risk. These results lay the groundwork for mechanistic/deconstruction experiments to identify critical bar components and putative synergistic combinations responsible for observed effects.
Subject(s)
Dietary Fiber/administration & dosage , Dietary Supplements , Fruit , Adult , Aged , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Female , Glutathione/blood , Homocysteine/blood , Humans , Lipoproteins, HDL/blood , Male , Middle Aged , Pilot Projects , RiskABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0240437.].
ABSTRACT
The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents.
Subject(s)
Biomarkers , Cardiology/standards , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Pediatrics/standards , Adolescent , Child , Humans , Risk FactorsABSTRACT
Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (-0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.
Subject(s)
Ceramides , Fructose , Pediatric Obesity , Biomarkers/metabolism , Cardiometabolic Risk Factors , Ceramides/metabolism , Child , Fructose/administration & dosage , Humans , Insulin Resistance/physiology , Lipogenesis , Liver/metabolismABSTRACT
Background: Myriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth. Methods: A pediatric cohort (N = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified. Clinical data were collected from the medical record and reserve plasma aliquots were assessed for lipoproteins by NMR spectroscopy and assayed for HDL functional cholesterol efflux capacity (CEC). Findings were compared by COVID-19 status and symptom severity. Lipoprotein, NMR spectroscopy and CEC data were compared with 30 outpatient COVID negative children. Results: Decreasing HDL cholesterol (HDL-c), apolipoprotein AI (ApoA-I), total, large and small HDL particles and HDL CEC showed a strong and direct linear dose-response relationship with increasing severity of COVID-19 symptoms. Youth with mild or no symptoms closely resembled the uninfected. An atypical lipoprotein that arises in the presence of severe hepatic inflammation, lipoprotein Z (LP-Z), was absent in COVID-19 negative controls but identified more often in youth with the most severe infections and the lowest HDL parameters. The relationship between HDL CEC and symptom severity and ApoA-I remained significant in a multiply adjusted model that also incorporated age, race/ethnicity, the presence of LP-Z and of GlycA, a composite biomarker reflecting multiple acute phase proteins. Conclusion: HDL parameters, especially HDL function, may help identify youth at risk of more severe consequences of COVID-19 and other novel infectious pathogens.
ABSTRACT
BACKGROUND: Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. METHODS: Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. RESULTS: The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. CONCLUSIONS: The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.
ABSTRACT
BACKGROUND: Poor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT). METHODS: Overweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured. RESULTS: In the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia. CONCLUSION: Nutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.
Subject(s)
Exercise Therapy/methods , Metabolomics/methods , Overweight/therapy , Plasma/chemistry , Adolescent , Adult , Counseling , Dietary Supplements , Family , Female , Humans , Life Style , Male , Middle Aged , Plasma/drug effects , Treatment OutcomeABSTRACT
AIM: To examine efficacy and predictors of response to a lifestyle intervention for obese youth. METHODS: Retrospective chart review of 214 children and adolescents aged 8-19 years. Linear regression identified baseline predictors of response (delta BMI z-score) at first and ultimate follow-up visits. RESULTS: Mean delta BMI z-score from baseline was -0.04 (p < 0.001) at first follow-up and -0.09 (p < 0.001) at ultimate follow-up (median time 10 mo) among 156 children and adolescents. Higher baseline BMI z-score predicted poor response at first and ultimate follow-up, explaining 10% of variance in response. Fasting insulin explained 6% of response variance at first follow-up. delta BMI z-score at the first visit along with baseline BMI z-score explained up to 50% of variance in response at ultimate visit. CONCLUSION: Clinic-based interventions improve weight status. Baseline variables predict only a small proportion of response; response at the first visit is a more meaningful tool to guide clinical decisions.
Subject(s)
Adolescent Behavior/physiology , Ambulatory Care , Behavior Therapy/methods , Biomarkers/analysis , Obesity/diagnosis , Obesity/therapy , Risk Reduction Behavior , Adolescent , Adult , Biomarkers/blood , Child , Diet Therapy , Female , Follow-Up Studies , Humans , Male , Motor Activity , Obesity/blood , Obesity/psychology , Prognosis , Retrospective Studies , Television , Treatment Outcome , Young AdultABSTRACT
This JCL Roundtable discussion probes the knowledge of 3 experts in pediatric lipidology, an emerging discipline both in the United States and internationally. In the 1990s, only 3 US institutions could be said to have dedicated pediatric lipid clinics; that number has grown to 25 today. The Pediatric Atherosclerosis Prevention and Lipidology Group of the National Lipid Association has regular teleconferences to support advocacy and convey best practices. Guidelines for pediatric lipidology initially focused on low-density lipoprotein cholesterol in 1992 as part of the National Cholesterol Education Program. Today the most comprehensive coverage comes from the 2011 National Heart Lung and Blood Institute Pediatric Guidelines. Universal screening was recommended for children between ages 9 and 11 years and teenagers/young adults between 17 to 21 years, a position echoed as "may be recommended" by the 2018 AHA/ACC/Multisociety Cholesterol Guidelines. While pediatric lipidologists continue to treat uncommon genetic disorders, they increasingly confront an issue of epidemic proportions-dyslipidemia as the initial presentation of metabolic dysregulation associated with obesity. Consequences of such altered metabolism extend to atherosclerosis, diabetes, liver disease, and other serious problems in adult life. Pediatric lipid science and practice differ from adult experience in several ways, including importance of family and birth history as well as genetics/epigenetics, lack of general pediatricians' familiarity with lipid drugs, value of family counseling, need for biomarkers of early metabolic dysregulation, and anticipation of endpoints in adult life not fully defined by randomized clinical trials in children.