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There is concern that high iron uptake during the critical period of early brain development carries potential risks, especially for nonanemic infants. This study examined the neurocognitive functioning of 16-year-olds who were nonanemic as infants and received iron supplementation.We studied 562 Chilean adolescents (Compared to adolescents in the no-added iron condition in infancy, those in the iron-supplemented condition had poorer visual-motor integration, quantitative reasoning skills, and incurred more errors on neurocognitive tasks. Consuming larger amounts of iron-fortified formula in infancy was associated with lower arithmetic achievement. Of adolescents who had high hemoglobin at 6 months (Hb ≥ 125 g/L), those in the iron supplemented condition had poorer performance on arithmetic, quantitative reasoning, and response inhibition tests than those in the no-added iron condition. Of adolescents who had marginally low 6-month hemoglobin (Hb100 and110 g/L), those who received no-added iron incurred more errors on a visual searching task than those in the iron-supplemented condition.The physiologic need for iron during the period of rapid and critical brain development in young infants should be considered vis-à-vis the risks associated with supplementing nonanemic infants with high levels of iron.

OBJECTIVE: This study examined how the lower cognitive skills in children who consumed iron-fortified formula in infancy relate to outcomes in young adulthood. METHODS: Participants were 443 Chilean young adults (M age = 21.2y, 55% female) who took part in a randomized controlled iron-deficiency anemia preventive trial during infancy (6-12m). Slightly over half of participants (n = 237) received iron-fortified formula (12.7 mg/L) and 206 received a low-iron formula (2.3 mg/L). Spatial memory, IQ, and visual-motor integration were measured at age 10, and neurocognition, emotion regulation, educational level, and attainment of adult developmental milestones were assessed at age 21. RESULTS: Consumption of iron-fortified formula in infancy was associated with poorer performance on neurocognitive tests in childhood, and these effects related to poorer neurocognitive, emotional, and educational outcomes in young adulthood. Dosage effects associated with consumption of iron-fortified formula were found for lower educational attainment and, marginally, slower mental processing. Those who received iron-fortified formula and had low age 10 cognitive abilities performed most poorly on neurocognitive tests at age 21. CONCLUSION: Findings suggest that the long-term development of infants who consume iron-fortified formula may be adversely affected.

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991–1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N=537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16y) and these values after 6 years of follow-up (22y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16y BF% and 22y leptin levels (β(SE): 0.58(0.06) for females; 0.53(0.05) for males), between 16y PTF and 22y adiponectin levels (β(SE): −0.31(0.06) for females; −0.18(0.06) for males) and between 16y adiponectin levels and 22y BF% (β(SE): 0.12(0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

BACKGROUND Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

To determine whether iron deficiency in infancy is associated with sluggish cognitive tempo (SCT) or attention-deficit/hyperactive-impulsive (AD-HI) symptoms in childhood and adolescence, and whether such behaviors contribute concurrently and predictively to lower verbal and mathematical abilities.Chilean children (Adjusting for a comprehensive panel of covariates, greater severity of iron deficiency in infancy was associated with more frequent SCT and AD-HI symptoms at all ages studied. Most effects of iron deficiency on children's verbal and math skills were indirect, mediated through AD-HI behaviors. Children's AD-HI symptoms related to lower verbal and math test scores within age and across age.The long-term associations found between infant iron deficiency and SCT and AD-HI behaviors suggest that the neurodevelopmental alterations that stem from postnatal iron deficiency might play an etiological role in the development of ADHD. Screening for early-life nutritional deficiencies among children with SCT or ADHD symptoms might prove useful, and behavioral screening of children with a history of iron deficiency seems warranted. Interventions that support brain development after early nutritional deprivation also would be beneficial.

Greater psychosocial risk in childhood and adolescence predicts poorer cardiometabolic outcomes in adulthood. We assessed whether the timing of psychosocial risk from infancy through adolescence predicts cardiometabolic outcomes in young adulthood. Young adults and their mothers participated in a longitudinal study beginning in infancy in Santiago, Chile (N = 1040). At infancy, 5 years, 10 years, and adolescence, mothers reported on depressive symptoms, stressful experiences, support for child development in the home, father absence, parental education, and socioeconomic status (SES) to create a psychosocial risk composite at each time point. Young adults (52.1% female; 21–27 years) provided fasting serum samples and participated in anthropometric and blood pressure (BP) assessments, including a dual-energy X-ray absorptiometry (DXA) scan for measuring body fat. Greater infant psychosocial risk was associated with a greater young adult metabolic syndrome score (β = 0.07, 95% confidence intervals (CI): 0.01 to 0.13, p = 0.02), a higher body mass index and waist circumference composite (β = 0.08, 95% CI: 0.03 to 0.13, p = 0.002), and a higher body fat (DXA) composite (β = 0.07, 95% CI: 0.01 to 0.12, p = 0.02). No psychosocial risk measure from any time point was associated with BP. Infant psychosocial risk predicted cardiometabolic outcomes in young adulthood better than psychosocial risk at 5 years, 10 years, or adolescence, mean of psychosocial risk from infancy through adolescence, and maximum of psychosocial risk at any one time. Consistent with the Developmental Origins of Health and Disease model, findings suggest that infancy is a sensitive period for psychosocial risk leading to poorer cardiometabolic outcomes in young adulthood.

Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

Objective Many children and adolescents are assessed for potential psychological and behavioral problems through the parent-completed Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) questionnaires. However, because these assessments are based on individual reports, they are subject to disagreement. This study considered multiple family factors and aspects of mothers' mental health in discrepancies between mothers' and youths' ratings on the CBCL and YSR. Method This study involved 926 mothers and their adolescent children (48.7% female children, mean age = 14.4 years) who completed the CBCL and YSR questionnaires, respectively. Results Mothers who experienced more severe mental health problems reported more internalizing symptoms of their adolescent relative to the adolescent's ratings. Conclusion Findings indicate that mothers' poor mental health is related to their reports of more frequent psychological problems in their adolescents. To verify the accuracy of maternal reports, additional raters and additional methods, such as behavioral observation and clinical interview, would be helpful.

Introduction This study examined changes in substance use from adolescence to young adulthood as related to adolescents’ risk taking, sensation seeking, antisocial activities, and personality traits. Methods Chilean youth (N = 890, 52% female) were studied in adolescence (14.5 and 16.2 years) and young adulthood (M age 21.3 years). Risk taking was assessed via a laboratory-based performance task (Balloon Analogue Risk Task), and self-administered questionnaires assessed sensation seeking, antisocial behaviors, personality and substance use. Results Frequent involvement in sensation seeking and antisocial activities were associated with increased odds of continued marijuana use from adolescence to young adulthood and of illicit substance use at young adulthood. High risk taking was associated with a reduced likelihood of discontinuing marijuana use at young adulthood, and high agreeableness and conscientiousness were associated with reduced likelihood of new onset marijuana use and illicit substance use at young adulthood. Conclusions Results highlight specific risk-taking tendencies and personality characteristics that relate to initiating, continuing, or discontinuing substance use at entry into adulthood. Sensation seeking and involvement in antisocial activities were the two foremost risk factors for continued use, which is a forecaster of drug dependence. Findings suggest potential prevention and intervention targets for abstaining from or discontinuing substance use as youth transition to adulthood.

Objective The aim of this study was to investigate whether the level, rate, and acceleration of BMI growth differ according to the presence or absence of adult cardiometabolic (CM) risks. Methods BMI was measured in 1,000 Chileans at nine time points from birth to 23 years, and metabolic syndrome and its components were assessed at young adulthood. BMI growth was analyzed in the following three developmental periods: birth to 6 months, 6 months to 5 years, and 5 to 23 years. Results Individuals with CM risks had a specific constellation of early-life growth (faster growth after infancy, lower BMI decline approaching age 5, absence of a definitive BMI nadir in early childhood, higher 5-year BMI) and distinct young adult growth (larger BMI increases from childhood to young adulthood and lower levels of expected growth deceleration approaching young adulthood). Those with CM risks also attained BMI ≥ 25 at significantly younger ages than those absent risks (metabolic syndrome: 12.3 years vs. 20.1 years; hyperglycemia: 13.1 years vs. 18.9 years; hypertension: 13.2 years vs. 19.4 years; hypertriglyceridemia: 14.3 years vs. 19.5 years; inflammation: 15.9 years vs. 20.6 years). Conclusions Larger and faster increases in BMI and a failure of BMI growth to decline or decelerate at specific developmental periods distinguished individuals who would and would not have adult CM risks.

BACKGROUND: Obesity is a risk factor for insulin resistance (IR) and metabolic disease. OBJECTIVE: To examine potential metabolic pathways linking childhood weight status to adolescent IR and metabolic risk. METHODS: Participants were 600 low- to middle-income Chilean adolescents from a cohort studied since infancy as part of an iron deficiency anemia preventive trial and follow-up study. We examined body mass index z-score at 10 years (BMIz-10y) and blood pressure, total fat, and fasting glucose, adiponectin to leptin ratio (A:L), ghrelin, and HOMA-IR at 16 years. A total count for metabolic risk factors (MRF) was calculated using the International Diabetes Federation criteria. We used path analysis to estimate pathways and model indirect effects from BMIz-10y, controlling for child age and sex and maternal body mass index (BMI). RESULTS: Participants were 54% male; mean BMIz-10y of 0.53 (SD=1.02); mean MRF of 1.3 (SD=0.9); mean HOMA-IR of 1.8 (SD=1.3). Path analysis showed that BMIz-10y directly and indirectly related to increased MRF via A:L and HOMA-IR. Ghrelin was not in the metabolic pathway from BMIz-10y to MRF but was related to MRF via HOMA-IR. CONCLUSION: These results elucidate metabolic pathways involving child weight status, IR and metabolic risk in adolescents. Childhood BMI was an indirect risk factor for adolescent cardiometabolic risk via several pathways that involved BMI, appetite hormones, markers of inflammation, and insulin resistance during adolescence. Findings illustrate the adverse effect that childhood obesity has on adolescent health outcomes, which sets precedence for health outcomes over the life course.

Obesity is the most important predisposing factor for cardiovascular disease and type-2 diabetes. We explored the relationship between the age at onset of obesity and selected cardiometabolic parameters in young adults. Longitudinal study of n = 1,039 participants (48% males) in their early twenties. BMI was measured at birth, 1–5–10–12–14–16–23 years. BMI trajectories were interpolated. Five groups were identified: never obese (never-OB); early childhood obesity transitioning to non-obesity before adolescence (former-OB); obesity starting in preadolescence transitioning to non-obesity as adolescents (transient-OB); obesity from adolescence into early adulthood (recent-onset-OB); participants who were obese in early childhood and remained obese into adulthood (persistent-OB). Waist circumference (WC), blood pressure, lipids, glucose, and insulin were measured at 23 years. HOMA-IR and the Metabolic Syndrome Risk Z-Score were estimated. In the sample, 47% were obese during at least one time-point. Mean obesity duration was 20.7 years, 8.5 years, 6.2 years, and 3.3 years in persistent-OBs, recent-onset-OBs, former-OBs, and transient-OBs, respectively. The cardiometabolic profile was more adverse in recent-onset-OBs (12%) and persistent-OBs (15%) compared to never-OB participants (53%). Although former-OBs (15%) and transient-OBs (4%) had higher WC values than never-OBs, no differences were seen in other biomarkers. Both persistent and recent-onset obesity led to a cardiometabolic profile of risk in early adulthood, as suggested by values of WC, HOMA-IR, and hs-CRP above normal limits and HDL-chol values below normal limits. Participants who had obesity in early childhood or preadolescence but transitioned to a non-obesity status had a cardiometabolic profile similar to participants who were never obese and within normal limits. Obesity leads to risky values in a number of cardiometabolic biomarkers in young adulthood independent of age at obesity onset. Likewise, overcoming obesity during the pediatric age leads to a cardiometabolic profile within normal ranges at 23 years of age.

Little is known regarding the relationship between adverse home environments and hormones important in regulation of appetite and their impact on obesity in children and adolescents. In this study, we examined the impact of socioeconomic economic status, family stress and maternal depressive symptoms on appetite hormones, adipokines and adiposity. To determine whether adverse home environments in childhood and adolescence relate to adiposity in adolescence and disruptions in appetite hormones and adipokines, specifically lower levels of adiponectin and ghrelin and elevated levels of leptin and orexin. Adversity in the home (maternal depressive symptoms, family stress, socioeconomic disadvantage) was measured in the households of 593 Chilean youth at age 10 years (52.3% male) and in 606 youth at 16 years. At 16 years, participants provided fasting blood samples for assessment of adipokines and appetite hormones. Waist-to-height ratio was used to assess central adiposity. Correlational analyses examined associations between continuous levels of adversity in childhood and adolescence and appetite hormones and adiposity in adolescence. Multinomial logistic regressions compared hormone levels by tertiles of adversity. Participants were 52% male, with average age at the 16 years hormone assessment being 16.8 (n = 606, SD = 0.26). Those with highest maternal depression at age 10 had lower adiponectin OR = 0.95 [95% CI: 0.91, 0.99], p = 0.005) and ghrelin levels (OR = 0.98 [95% CI: 0.98, 1.00), p = 0.022) than those in the lowest maternal depression group at age 16. Those with the highest family stress at 16 years had lower adiponectin levels (OR = 0.93 [95% CI: 0.89, 0.98), p = 0.004) and higher central adiposity (OR = 1.05 [1.01, 1.08], p = 0.009) than the lowest family stress group. There were no significant associations found between socioeconomic status at either 10 or 16 years and appetite hormones. Results add new evidence regarding the relationship between household adversity to appetite hormones and adipokines, with the most consistent results for adiponectin. Current findings suggest that the relationship between home environment and adipokines and appetite hormones may play a role in altered adiposity in children and adolescents.

This study examines the extent to which iron deficiency in infancy contributes to adverse neurocognitive and educational outcomes in young adulthood directly and indirectly, through its influence on verbal cognition and attention problems in childhood. Young adults (N = 1,000, M age = 21.3 years, 52% female; of Spanish or indigenous descent) from working-class families in Santiago, Chile, completed instruments assessing memory, processing speed, mental flexibility, and educational attainment. Iron status was assessed at ages 6, 12, and 18 months, and verbal intelligence, inattention, and sluggish cognitive tempo (SCT) symptoms were assessed at age 10. Results indicated that young adults who had iron-deficiency in infancy had poor executive control at age 21. Severity of iron deficiency during infancy was associated with lower verbal IQ and more frequent inattention and SCT symptoms in childhood, and with lower educational attainment in young adulthood through its effect on inattention. No additional indirect effects were found. Interventions directed toward improving cognitive and attention deficits linked to early-life iron deficiency appear warranted and could alter the course to adult functioning. Further research on the impact of such interventions would be helpful. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Appetite regulation is integral to food intake and is modulated by complex interactions between internal and external stimuli. Hormonal mechanisms which stimulate or inhibit intake have been characterized, but the physiologic effects of serum levels of such hormones in short-term appetite regulation have received little attention.To evaluate whether fasting levels of orexigenic/anorexigenic hormones were associated with energy intake at breakfast, served soon after drawing a fasting blood sample, in a group of adolescents.Anthropometry, body composition and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured in 655 Chilean adolescents aged 16.8 ± 0.3 years (52% males). Energy intake was measured at a semi-standardized breakfast. Associations between hormone levels and energy intake were studied using multivariate linear models.Thirty nine percent of participants were overweight/ obese. After an overnight fast, median values for leptin, insulin, ghrelin and orexin-A were 7.3 ng/mL, 6.7 IU/dL, 200.8 pg/mL, and 16.1 pg/mL, respectively. Participants ate on average 637 ± 239 calories at breakfast. In multivariable models, insulin levels were inversely and independently associated with caloric intake at breakfast (β = -18.65; p0.05), whereas leptin, ghrelin and orexin-A levels were positively and independently associated with intake: β= 5.56, β = 0.34 and β = 8.40, respectively, p0.05.Fasting leptin, ghrelin and orexin-A were positively associated with energy intake during breakfast provided soon after the blood draw. Insulin was negatively associated with energy intake. Modifiable factors influencing levels of appetite regulating hormones could be a potential target for influencing food intake.

AimTo explore the association of selected cardiometabolic biomarkers and metabolic syndrome (MetS) with educational outcomes in adolescents from Chile.MethodsOf 678 participants, 632 (52% males) met criteria for the study. At 16 years, waist circumference (WC), systolic blood pressure, triglycerides (TG), high-density lipoprotein and glucose were measured. A continuous cardiometabolic risk score (zMetS) using indicators of obesity, lipids, glucose and blood pressure was computed, with lower values denoting a healthier cardiometabolic profile. MetS was diagnosed with the International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute joint criteria. Data on high school (HS) graduation, grade point average (GPA), college examination rates and college test scores were collected. Data were analysed controlling for sociodemographic, lifestyle and educational confounders.ResultzMetS, WC, TG and homeostatic model assessment of insulin resistance at 16 years were negatively and significantly associated with the odds of completing HS and taking college exams. Notably, for a one-unit increase in zMetS, we found 52% (OR: 0.48, 95% CI 0.227 to 0.98) and 39% (OR: 0.61, 95% CI 0.28 to 0.93) reduction in the odds of HS completion and taking college exams, respectively. The odds of HS completion and taking college exams in participants with MetS were 37% (95% CI 0.14 to 0.98) and 33% (95% CI 0.15 to 0.79) that of participants with no cardiometabolic risk factors. Compared with adolescents with no risk factors, those with MetS had lower GPA (515 vs 461 points; p=0.002; Cohen’s d=0.55). Adolescents having the MetS had significantly lower odds of passing the mathematics exam for college compared with peers with no cardiometabolic risk factors (OR: 0.49; 95% CI 0.16 to 0.95).ConclusionIn Chilean adolescents, cardiometabolic health was associated with educational outcomes.

Background: The contribution of long-term vs. recent-onset obesity to cardiometabolic risk in adolescence remains controversial. Objective: To investigate the association of time of onset and length of obesity with the cardiometabolic profile of adolescence. Methods: Prospective study in 678 16-year-olds. BMI was measured at birth-1-5-10-16y and BMI trajectories were interpolated using cubic splines. BMI >2 sd at

The purpose of this study was to assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of 21-year-olds from Santiago, Chile, a setting where laws relating to marijuana cultivation have recently been relaxed. Participants (n=654) reported marijuana use frequency, age of first use and whether use led to problems in their lives and participated in cognitive testing of learning and memory—Cogstate International Shopping List. Marijuana use was reported as ever (69.5%), during past year (45.8%), and past 30 days (27.0%). Those who used during the past 30 days scored lower on delayed recall (p

Background: We aimed to determine the sensitivity and specificity of selected anthropometric indicators as predictors of cardiovascular risk in adolescents. Methods: Cross-sectional study in 678 adolescents (16.8y ± 0.3) from an infancy cohort. Weight, height, waist circumference (WC) and hip circumference were measured. Body-Mass Index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated. MetS was diagnosed with IDF/AHA/NHLBI. Optimal cutoffs of BMI, WC, WHR and WHtR for diagnosing MetS were determined using ROC analysis. Results: In males, WHtR (0.96) had the greatest area under the ROC curve, followed by WC (0.95) and BMI (0.93). In females, BMI (0.84) had the greatest area under the ROC curve (0.84), followed by WHtR (0.83) and WC (0.83). In both sexes, the optimal WHtR cutoff for MetS diagnosis was 0.54. A BMI of 26.9 in males and 26.3 in females were the optimal cutoffs for diagnosing MetS. Finally, WC values of 92 and 81.6 cm in males and females, respectively, were the optimal cutoffs for MetS diagnosis. Conclusions: In both sexes, a WHtR value of 0.54 was a good predictor of MetS. In males and females, the optimal cutoff of BMI for Mets diagnosis was below the values for diagnosing obesity.

Introduction: Adipose tissue secretes adipokines such as adiponectin and leptin playing important roles in energy metabolism. Adiponectin has a protective effect against cardiometabolic diseases (CMD), whereas leptin increases risk of CMD. Although associations between plasma adipokines and body fat mass have been established, most have been cross-sectional, limiting causal inferences. Hypothesis: We hypothesize that 1. adipokines can affect body fat accumulation via the regulation of energy homeostasis and 2. adipose tissue can affect the amount of adipokines secreted. Thus, we assessed the associations between body fat percent (BF%) and adipokines during adolescence and 6 years later. Methods: Measurements for plasma leptin (N=622) and adiponectin (N=565) were available at age 16 and 22 in participants from the Santiago Longitudinal Study. BF% was measured by dual X-ray absorptiometry. Structural equation models were used to estimate longitudinal associations of BF% and adipokines at baseline and with 6-year changes in these values, adjusted for sex, time to follow-up, baseline age, physical activity, nutrition quality, smoking status, and alcohol consumption. Results: Effect estimates are shown in Figure 1 . We found evidence of association between baseline adipokine and BF% change and baseline BF% and adipokine change with the one notable exception a lack of association between baseline BF% and adiponectin change. Conclusions: Leptin and BF% were positively associated longitudinally, but the longitudinal associations between adiponectin and BF% were counterintuitive or non-significant. While there might be a close long-term relationship between leptin levels and body fat accumulation, the long-term relationship between adiponectin levels and body fat accumulation might develop after the adolescence and young adulthood transition.

Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors.We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling.We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels.The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers.This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Background: Stress can affect appetite via disruptions in appetite hormones and adipokines. Stress triggered by an adverse home environment might also relate to appetite. Objective: To determine whether adverse home environments in childhood and adolescence relate to disruptions in appetite hormones in adolescence, or specifically, lower levels of adiponectin and ghrelin and higher levels of leptin and orexin. Methods: Home environments were measured for forms/types of adversity (i.e., depression, family stress, …

To compare approaches for adjusting serum ferritin concentrations for inflammation in Chilean adolescents with overweight and obesity.Cross-sectional data from 518 adolescents (aged 16-17 years; 48% females) from Santiago, Chile were analyzed. Several approaches were compared for estimating the prevalence of depleted iron stores (defined as serum ferritin15 μg/L), including unadjusted prevalence and higher cutoffs for various subgroups (excluding participants with inflammation), correction factors, and regression corrections. A "reference" prevalence estimate was calculated as the prevalence of serum ferritin15 μg/L in normal weight individuals without inflammation. Each adjustment approach was compared with this reference prevalence.The sample comprised 61.2% normal weight, 23.7% overweight, and 15.1% obese individuals. The prevalence of inflammation (marked by C-reactive protein level5.0 mg/L) was 6.3%, 8.1%, and 14.1% in the 3 groups, respectively. The correction factor approaches produced adjusted estimates closest to the reference estimate (24.1%-24.7% vs 22.9%), followed by the regression corrections (24.7%-25.1% vs 22.9%). Applying a higher serum ferritin cutoff (30 μg/L) to all participants or to participants with overweight/obesity produced adjusted estimates farthest from the reference (59.5% and 35.3%, respectively).Adjusting serum ferritin concentration may be necessary when assessing iron status in populations with high rates of overweight/obesity. After reviewing 6 approaches for adjusting for the influence of inflammation, this study suggests that using correction factors may be the most appropriate approach for adjusting serum ferritin in Chilean adolescents. Further research is needed to determine the optimal approach for adjusting serum ferritin concentrations for weight-related inflammation in broader populations.

Insulin measurements are not advised for cardiometabolic risk screening in large groups. Here we assessed the accuracy of the single-point insulin sensitivity estimator (SPISE) to diagnose cardiometabolic risk in Chilean adolescents. In 678 post-pubertal adolescents (52% males, M(SD) age = 16.8 (0.2) years), height, weight, waist circumference, blood lipids, glucose, insulin, and blood pressure were measured. BMI, HOMA-IR, and SPISE were estimated; HOMA-IR values ≥ 2.6 were considered insulin resistance (IR). Metabolic syndrome (MetS) was defined with the joint IDF/AHA/NHBLI standard. Using receiver operating characteristic curves, we obtained optimal SPISE cutpoints for IR and MetS diagnosis. The prevalence of MetS and IR was 8.2% and 17.1%, respectively. In males, the optimal cutoff for MetS diagnosis was 5.0 (sensitivity: 97%; specificity: 82%), and the optimal cutoff for IR diagnosis was 5.9 (sensitivity: 71%; specificity: 83%). In females, a SPISE of 6.0 had the highest sensitivity (90%) and specificity (74%) for MetS diagnosis. A SPISE of 6.4 was the optimal cutoff for IR diagnosis; however, sensitivity and specificity were 61% and 75%. In males and female post-pubertal adolescents, SPISE had a very good and good diagnostic performance, respectively, in predicting MetS. It was an accurate diagnostic tool for IR prediction in males, but not necessarily in females.

BACKGROUND: The genetic underpinnings of glycemic traits have been understudied in adolescent and Hispanic/Latino (H/L) populations in comparison to adults and populations of European ancestry. OBJECTIVE: To identify genetic factors underlying glycemic traits in an adolescent H/L population. METHODS: We conducted a genome-wide association study (GWAS) of fasting glucose (FG) and fasting insulin (FI) in H/L adolescents from the Santiago Longitudinal Study. RESULTS: We identified one novel variant positioned in the CSMD1 gene on chromosome 8 (rs77465890, effect allele frequency=0.10) that was associated with FI (β=−0.299, SE=0.054, p=2.72×10(−8)) and was only slightly attenuated after adjusting for body mass index z-scores (β=−0.252, SE=0.047, p=1.03×10(−7)). We demonstrated directionally consistent, but not statistically significant results in African and Hispanic adults of the Population Architecture Using Genomics and Epidemiology Consortium. We also identified secondary signals for two FG loci after conditioning on known variants, which demonstrate allelic heterogeneity in well-known glucose loci. CONCLUSION: Our results exemplify the importance of including populations with diverse ancestral origin and adolescent participants in GWAS of glycemic traits to uncover novel risk loci and expand our understanding of disease etiology.

An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) as the reference. The study was conducted in youths from an ongoing cohort study. Clinical validation was performed, using receiver operating characteristic analysis, in n = 60 participants (22.6y; 50% males). Abdominal ultrasound was carried out with liver brightness (score 0–3), diaphragm attenuation (0–2) and liver vessel blurring (0–1) scored by two observers. Liver fat was estimated using MRS. Then, analytical validation was conducted in the remaining participants (n = 555; 22.7y; 51% males) using effects size estimates. An ultrasound score ≥4.0 had the highest sensitivity (78%) and specificity (85%) for NAFLD diagnosis. An area under the curve of 86% denotes a good diagnostic performance of the test, whereas a Kappa of 0.63 suggests substantial agreement of ultrasound vs. MRS. The analytical validation showed that participants having NAFLD according to ultrasound had an unhealthier cardiometabolic profile than participants without the condition. Abdominal ultrasound, combined with a semi-quantitative score system, is a reliable method to determine liver fat infiltration in young adults and should be encouraged whenever MRS is unavailable.

ObjectivesInfant anthropometric growth varies across socioeconomic factors, including maternal education and income, and may serve as an indicator of environmental influences in early life with long-term health consequences. Previous research has identified sociodemographic gradients in growth with a focus on the first year and beyond, but estimates are sparse for growth before 6 months. Thus, our objective was to examine the relationship between sociodemographic factors and infant growth patterns between birth and 5 months of age.DesignProspective cohort study.SettingsLow-income to middle-income neighbourhoods in Santiago, Chile (1991–1996).Participants1412 participants from a randomised iron-deficiency anaemia preventive trial in healthy infants.Main outcome measuresLongitudinal anthropometrics including monthly weight (kg), length (cm) and weight-for-length (WFL) values. For each measure, we estimated three individual-level growth parameters (size, timing and velocity) from SuperImposition by Translation and Rotation models. Size and timing changes represent vertical and horizontal growth curve shifts, respectively, and velocity change represents growth rate shifts. We estimated the linear association between growth parameters and gestational age, maternal age, education and socioeconomic position (SEP).ResultsLower SEP was associated with a slower linear (length) velocity growth parameter (−0.22, 95% CI –0.31 to –0.13)—outcome units are per cent change in velocity from the average growth curve. Lower SEP was associated with later WFL growth timing as demonstrated through the tempo growth parameter for females (0.25, 95% CI 0.05 to 0.42)—outcome units are shifts in days from the average growth curve. We found no evidence of associations between SEP and the weight size, timing or velocity growth rate parameters.ConclusionPrevious research on growth in older infants and children shows associations between lower SEP with slower length velocity. We found evidence supporting this association in the first 5 months of life, which may inform age-specific prevention efforts aimed at infant length growth.

Aim We investigated the relation of time of onset and length of obesity with biomarkers of β-cell function in early adulthood in an infancy cohort. Material and methods In 1039 23-year-olds, body-mass index (BMI) was measured at multiple time-points from enrollment. BMI trajectories were interpolated with cubic polynomials. Fasting glucose, insulin and adiponectin were measured at 23 years. Homeostatic model assessment-insulin resistance (HOMA-IR), HOMA-S, HOMA-β, HOMA-adiponectin (AD) and disposition index (DI) were estimated. IR and non-alcoholic fatty liver (NAFL) were diagnosed. According to the BMI trajectory, five groups were defined: participants who were never obese (NOB); participants with obesity starting in adolescence and remained obese into adulthood (recent-onset obesity, ROB); participants who were obese in early childhood but transitioned to non-obesity as preadolescents (former obesity, FOB); participants who were obese in early childhood and remained obese into adulthood (persistent obesity, POB); participants with obesity starting in preadolescence and transitioned to non-obesity as adolescents (transient obesity; TOB). Results Obesity was present in 47% of participants during at least one time-point. ROBs and POBs had higher insulin, HOMA-IR and HOMA-β, lower HOMA-S and DI, and higher prevalence of IR and NAFL at 23 years than NOBs, TOBs and FOBs. No differences were found in the β-cell functionality of NOBs, TOBs and FOBs. Conclusions Persistent and recent obesity are both related to IR, NAFL and a decline of β-cell function in emerging adulthood. Defeating obesity in childhood or adolescence allows reaching emerging adulthood with β-cell functioning similar to that of subjects who were NOB.

ObjectiveThe present longitudinal study assessed whether changes in socio-economic status (SES) from infancy to adolescence were associated with plasma lipoprotein concentrations in adolescence, of which low HDL-cholesterol (HDL-C) and high LDL-cholesterol (LDL-C), TAG and total cholesterol (TC) concentrations are associated with higher cardiovascular risk.DesignSES, assessed using the modified Graffar Index, was calculated at 1, 5, 10 and 16 years. Principal components factor analysis with varimax rotation extracted two orthogonal SES factors, termed ‘environmental capital’ and ‘social capital’. Generalized linear models were used to analyse associations between environmental and social capital at 1 and 16 years and outcomes (HDL-C, LDL-C, TAG, TC) at 16 years, as well as changes in environmental and social capital from 1–5, 5–10, 10–16 and 1–16 years, and outcomes at 16 years.SettingSantiago, Chile.ParticipantsWe evaluated 665 participants from the Santiago Longitudinal Study enrolled at infancy in Fe-deficiency anaemia studies and examined every 5 years to age 16 years.ResultsSocial capital in infancy was associated with higher HDL-C in adolescence. Environmental capital in adolescence was associated with higher LDL-C and TC during adolescence. Changing environmental capital from 1–16 years was associated with higher LDL-C. Changing environmental capital from 1–5 and 1–16 years was associated with higher TC.ConclusionsImprovements in environmental capital throughout childhood were associated with less healthy LDL-C and TC concentrations in adolescence. We found no evidence of associations between changing environmental capital and HDL-C or TAG, or changing social capital and HDL-C, LDL-C, TAG or TC.

Little is known regarding the relationship between early life factors and bone mineral density (BMD). We found a positive association between breastfeeding for at least 6 months, without formula supplementation, and whole body adolescent BMD z-score. The aim of the study is to assess the role of breastfeeding BF on adolescent bone mineral density (BMD) in a cohort prospectively followed since infancy. We studied 679 participants from an infancy iron deficiency anemia preventive trial in Santiago, Chile, followed to adolescence. Breast and bottle feeding were ascertained weekly from 4 to 12 months. At 16 years, whole body BMD was assessed by DEXA. Using linear regression, we evaluated associations between BF duration and BF as the sole source of milk and adolescent BMD z-score, adjusting for possible infancy, adolescent, and background confounders. Mean birth weight and length were 3.5 (0.3) kg and 50.7 (1.6) cm. For at least 6 months, BF was the sole source of milk for 26.3% and with supplementation for 36.7%. For 37%, BF was provided for less than 6 months. Mean 16-year BMD z-score was 0.25 (1.0). Covariates included male sex, birth length, and gestational age. BF as the sole source of milk ≥6 months, compared to BF

SummaryBackground Early life factors can programme future risk for cardiovascular disease. Objectives We explored associations between adolescent adiponectin levels and concomitant metabolic alteration and also looked at the association between early life factors and adolescent adiponectin levels. Methods We studied a longitudinal cohort of low-income to middle-income Chilean adolescents who were enroled in an infancy iron-deficiency anaemia preventive trial and follow-up studies at the Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile. In the 577 adolescents who were assessed as part of the 16-year follow-up, we evaluated independent associations between adiponectin levels and metabolic disturbances during adolescence. We also assessed the association between early life factors [short breastfeeding {

Objective Stress derived from socioeconomic disadvantage can be damaging to mental and physical health. This study uses longitudinal data on a large prospectively studied cohort to examine how socioeconomic hardship during childhood leads to hypertension in young adulthood by its effects on family conflict, anxiety-depression, and body mass. Method Data are from 1,039 participants of the Santiago Longitudinal Study who were studied in childhood (M age 10 years), adolescence (14-17 years), and young adulthood (21-26 years). As young adults, 26% had elevated blood pressure or hypertension. Results Children from more economically disadvantaged families experienced higher levels of family conflict, which related to significant increases in anxiety-depression and body mass over time, both of which were directly linked to hypertension in young adulthood. Conclusions Findings provide an understanding of how early-life adversity associated with socioeconomic hardship manifests as stress-related health problems in adulthood. Intervention efforts that target overweight/obesity and anxiety and depression that stem from childhood poverty might be useful for reducing the socioeconomic disparities in adult health.

Background Notable weight gain is observed during young adulthood, compared to other adult age groups, yet the relation between eating behavior and body composition at this stage remains poorly understood. Objective The aim of this cross-sectional study was to assess the association between eating behavior scores (cognitive restraint, uncontrolled eating, and emotional eating), and body composition in a sample of Chilean young adults. Methods Logistic and linear regression models assessed the independent associations between cognitive restraint, uncontrolled eating, and emotional eating, derived from the Three Factor Eating Questionnaire-R18, and body mass index (BMI), percent body fat by dual-energy X-ray absorptiometry, and central obesity, accounting for demographic covariates, stratified by sex, in a sample of 555 participants of the Santiago Longitudinal Study (mean age 22.6 years [SD 0.4]). Results Cognitive restraint was positively associated with obesity, defined by BMI, % body fat, and central obesity. Emotional eating was related to obesity, defined by % body fat and central obesity in men and women and to obesity, defined by BMI, in women. Cognitive restraint was related to BMI in men and % body fat in women. Uncontrolled eating was not associated with adiposity in men or women. Conclusions In Chilean young adults, cognitive restraint and emotional eating scores were associated with higher BMI, elevated percent body fat, and greater central obesity.

Polyunsaturated fatty acids (PUFA) have been related to the development of adiposity. N-3 PUFA appears to be protective against obesity risk, while n-6 PUFA may be associated with greater adiposity. However, most studies have been conducted among adults. The role of PUFA in infancy is unknown.To examine associations of serum PUFA at age 1 year with age- and sex-adjusted body mass index Z score (BMIZ) change through age 16 years and body composition at 16 years.We quantified serum PUFA in 636 Chilean infants aged 1 year. We measured BMIZ at ages 1, 5, 10 and 16 years, and body composition by dual energy X-ray absorptiometry at 16 years. We estimated differences in 1- to 16-years BMIZ change between PUFA quartiles from multivariable linear mixed models with restricted cubic splines. At 16 years, we estimated differences in total fat mass (ToFM), truncal fat mass (TrFM), total lean mass (TLM), percent total fat mass (%ToFM) and percent truncal fat mass (%TrFM) between PUFA quartiles using linear regression.PUFA were not associated with BMIZ change. Alpha-linolenic acid (ALA) was positively associated with TrFM (P = .03) and %TrFM (P .0001) at 16 years while eicosapentaenoic acid (EPA) was inversely associated with %TrFM (P = .001). Docosapentaenoic acid (DPA) was positively associated with ToFM (P = .01), TrFM (P = .009), %ToFM (P = .02) and %TrFM (P = .02). Gamma-linolenic acid (GLA) and the Δ6-desaturase (D6D) activity index were each positively, linearly associated with ToFM, TrFM and %ToFM. The Δ5-desaturase (D5D) activity index was inversely associated with %TrFM (P = .04).ALA, DPA, GLA and the D6D index at 1 year of age were positively associated with adiposity at age 16 years, while EPA and the D5D index were inversely associated with central adiposity. Our results related to EPA and desaturase indices are in agreement with limited prior studies.

Early adversity, depression, and obesity are associated with increases in low-grade inflammation. However, there are few prospective and longitudinal studies to elucidate how these associations unfold in children. The present study used latent growth curve models to examine pathways between family adversity in infancy, depressive symptoms in childhood, body mass index (BMI) in childhood, and inflammation in adolescence (age = 16–18). The study is an adolescent follow-up of infants from working-class communities around Santiago, Chile, who participated in a preventive trial of iron supplementation at 6 months of age. Anthropometrics, stressful life events, maternal depression, socioeconomic status, and developmental assessments were measured at 12 months, 5 years, 10 years, and adolescence. In adolescence, participants provided blood samples for high-sensitivity C-reactive protein (hsCRP) assessment. Greater exposure to early adversity in the form of interpersonal conflict stress in infancy indirectly associated with increased hsCRP through its association to increased intercept and slope of childhood BMI. Depressive symptoms at any time were not directly or indirectly associated with increased hsCRP. These findings contribute to our understanding of how early family adversity and its associations with obesity and depressive symptoms across childhood are linked to low-grade, chronic inflammation in adolescence. The model identified as best capturing the data supported the pivotal role of childhood BMI in explaining how early-life adversity is associated with inflammation in adolescence.