It's About Timing: Contrasting the Metabolic Effects of Early vs. Late Time-Restricted Eating in Humans.

PURPOSE OF REVIEW: Time-restricted eating (TRE), a form of intermittent fasting, restricts feeding time across the day, imposing a daily 'eating window'. The time of day when the eating window occurs could result in differential metabolic effects. Here, we describe recent intervention studies in humans assessing the metabolic consequences of an early- (i.e., eating window starting in the early morning) vs. late (i.e., eating window starting after midday)-TRE protocol. RECENT FINDINGS: Well-controlled studies indicate that both TRE protocols effectively reduce body weight and improve altered glucose metabolism, lipid profile, inflammation, or blood pressure levels. An early-TRE (e-TRE) might have a further positive impact on improving blood glucose, insulin levels, and insulin resistance. However, the studies directly assessing the metabolic consequences of an early- vs. late-TRE have shown dissimilar findings, and more well-controlled clinical trials are needed on the metabolic benefits of these two types of TRE. Evidence suggests that an e-TRE might have enhanced metabolic results, particularly regarding glucose homeostasis. More long-term studies, including larger sample sizes, are needed to assess the metabolic, circadian, and adherence benefits, together with socio-cultural acceptance of both TRE approaches.

Associations between Adolescent Alcohol Use and Neurocognitive Functioning in Young Adulthood.

This study examined the associations between excessive alcohol intake during adolescence and neurocognitive functioning in young adulthood and whether these relations varied by sex. Participants were working-class Chilean adolescents (N = 692; Mage 16.0 years; 54.5% female) who provided frequency of past 30-day bingeing and past-year intoxication. Neurocognitive measures were completed in young adulthood (Mage 21.2 years). Illicit substance users were excluded a priori and other substance use was controlled. When males and females were considered simultaneously, no main effects of intoxication or bingeing were found. However, several sex-specific effects emerged for intoxication, such that more frequent intoxication was associated with poorer visual memory, attention, processing speed, response inhibition, and cognitive flexibility in females, while frequent intoxication related to better attention and processing speed in males. In general, effect sizes were small. No relations emerged for verbal memory, working memory, or spatial learning. Possible factors that contribute to divergent sex effects are discussed.

Socioeconomic position and executive functioning from childhood to young adulthood: Evidence from Santiago, Chile.

BACKGROUND: Optimizing cognitive development through early adulthood has implications for population health. This study aims to understand how socioeconomic position (SEP) across development relates to executive functioning. We evaluate three frameworks in life-course epidemiology - the sensitive period, accumulation, and social mobility hypotheses. METHODS: Participants were young adults from Santiago, Chile who were studied from 6 months to 21 years. Family SEP was measured at ages 1 y, 10 y, and 16 y with the modified Graffar Index. Executive functioning was assessed at ages 16 y and 21 y by the Trail Making Test Part B (Trails B). Analyses estimating 16 y and 21 y executive function involved 581 and 469 participants, respectively. Trails B scores were modeled as a function of SEP at 1 y, 10 y, and 16 y, as the total accumulation of disadvantage, and as change in SEP between 1 y and 10 y and between 10 y and 16 y. RESULTS: Participants were low- to middle-income in infancy and, on average, experienced upwards mobility across childhood. Half of participants (58%) improved Trails B scores from 16 y and 21 y. Most (68%) experienced upward social mobility between infancy and 16 y. When examined independently, worse SEP measured at 10 y and 16 y related to worse (longer time to complete) Trails B scores at Age 21 but did not relate to the other outcomes. After mutual adjustment as a test of the sensitivity hypothesis, no SEP measure was independently related to any outcome. Testing the accumulation hypothesis, cumulative low SEP was associated with worse cognitive performance at 21 y (ß = 3.6, p = 0.04). Results for the social mobility hypothesis showed no relation to cognitive scores or to change in cognitive scores. Comparing all hypotheses, SEP at 16 y explained the most variability in executive functioning at 21 y, providing support for the sensitive period hypothesis. CONCLUSIONS: Results indicate that experiencing cumulatively low socioeconomic position from infancy to adolescence can have a negative impact on cognitive functioning in young adulthood. Findings also provide evidence in support of adolescence as a key developmental period during which SEP can most strongly impact cognitive functioning.

Breastfeeding Duration and Timing of Bottle Supplementation: Associations with Body Mass Index from Childhood to Young-Adulthood.

Evidence for the association between breastfeeding (BF) duration and later body mass index (BMI) is inconsistent. We explored how BF duration and BF type (exclusive or partial) related to BMI from childhood to young adulthood in a Chilean cohort. Infants were recruited at 6 months between 1994 and 1996 in Santiago, Chile (n = 821). Mothers reported date of first bottle and last BF; anthropometry was measured at 1, 5, 10, 16, and 23 years. We tested whether: (1) type of BF at 6 months (none, partial, exclusive) and (2) duration of exclusive BF (<1 month, 1 to <3 months, 3 to <6 months, and ≥6 months) related to BMI. At 6 months, 35% received both breastmilk and formula ("partial BF") and 38% were exclusively breastfed. We found some evidence of an association between longer BF and lower BMI z-scores at young ages but observed null effects for later BMI. Specifically, BF for 3 to <6 months compared to <1 month related to lower BMI z-scores at 1 and 5 years (both p < 0.05). Our results are in partial accordance with others who have not found a protective effect of longer BF for lower BMI.

Adolescent sedentary behavior and body composition in early adulthood: results from a cohort study.

BACKGROUND: This study investigates the cross-sectional and prospective associations between accelerometer-measured sedentary behavior and body composition from adolescence to early adulthood. METHODS: Data from the Santiago Longitudinal Study were analyzed (n = 212). Sedentary time was measured at age 16 years, and body composition (body mass index [BMI], waist circumference, waist-to-height ratio [WHtR], fat mass percentage, and lean mass percentage) was examined at both age 16 and 23 years. Adjusted linear regression models estimated associations between sedentary time, sedentary bout duration, and body composition, overall and by sex. RESULTS: In all analyses, mean sedentary bout duration was not associated with body composition. In cross-sectional analyses, more sedentary time during adolescence was significantly associated with lower BMI, waist circumference, WHtR, fat mass percentage, and higher lean mass percentage (p < 0.05). One standard deviation increase in daily sedentary time was prospectively associated with lower body mass index (ß = -1.22 kg/m2, 95% CI: -2.02, -0.42), waist circumference (ß = -2.39 cm, 95% CI: -4.03, -0.75), and WHtR (ß = -0.014, 95% CI: -0.024, -0.004). Sedentary time at 16 years was not associated with changes in body composition from 16 to 23 years. CONCLUSIONS: Sedentary behavior in adolescence is not adversely associated with body composition profiles in early adulthood. IMPACT: Little is known about the effect of device-measured sedentary behavior on body composition during the transition from adolescence to early adulthood. Among participants in the Santiago Longitudinal Study, more accelerometer-measured sedentary time during adolescence was associated with lower BMI, waist circumference, and waist-to-height ratio in early adulthood though point estimates were generally small in magnitude. Sedentary behavior in adolescence was not detrimentally associated with healthy body composition profiles in early adulthood. Public health interventions aimed at reducing obesity rates could consider other behaviors, such as physical activity and healthy diet, instead of sitting time.

Ingesta de calcio y densidad mineral ósea en adolescentes chilenos con desarrollo puberal completo

Introducción: La cantidad diaria recomendada (RDA) de calcio en adolescentes es de 1.300 mg/día. La última Encuesta Nacional de Consumo Alimentario de Chile, mostró que la mediana de ingesta total de calcio fue menos de la mitad de la RDA. Una ingesta insuficiente de calcio puede impactar negativamente la mineralización ósea. Objetivo: Determinar el efecto de la ingesta de calcio y estado nutricional sobre la densidad mineral ósea (DMO) de adolescentes con desarrollo puberal completo. Métodos: Estudio de corte transversal. Participaron n= 79 adolescentes de ambos sexos de entre 17 y 18 años elegidos al azar, aparentemente sanos, estadio Tanner 5 e IMC-1 DE). Según estado nutricional, no hubo diferencias significativas en la ingesta de nutrientes, pero sí en la DMO. En media, la DMO estandarizada (puntaje Z) fue normal para ambos sexos (>-1 DE); los adolescentes con obesidad presentaron una DMO estandarizada significativamente mayor que los adolescentes de peso normal (1,05±0,85 vs 0.33±0,86; P= 0,04). La ingesta de calcio no se relacionó con la masa ósea total ni con la DMO estandarizada. Conclusión: En adolescentes con desarrollo puberal completo no hubo relación entre la ingesta de calcio y los niveles de mineralización ósea. Sí hubo relación entre mineralización ósea y estado nutricional, siendo mayor la DMO en los individuos con obesidad.

Background: In adolescents, the recommended daily intake (RDI) of calcium is 1,300 mg. In Chile, the latest National Survey of Food Consumption showed that the median total calcium intake was less than half of the RDI. An adequate intake of calcium in adolescence negatively affects BMD. Aim: To determine the association of calcium intake and nutritional status with bone mineral density (BMD) in male and female adolescents with completed pubertal development (Tanner 5). Methods: Cross-sectional study in a random sample of 79 male and female adolescents, ages 17-18. Participants were healthy, Tanner stage 5, and BMI −1 SD. BMD was higher in obese participants compared to normal-weight adolescents (1.05±0.85 vs 0.33±0.86; P= 0.04), although no differences in nutrients and food intake. Calcium intake was unrelated to total bone mass and unstandardized BMD. Conclusions: In our sample of adolescents with complete pubertal development, there was no relationship between calcium intake and bone mineralization levels. There was a significant relationship between bone mineralization and nutritional status, with BMD being higher in adolescents with obesity.

A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity.

Background: The Single-Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity estimated using BMI and triglycerides and high-density lipoprotein cholesterol. We assessed the accuracy of SPISE to screen obesity-related cardiometabolic risk in children and adolescents. Method: Cross-sectional validation study for a screening test in a sample of n=725 children and adolescents from an obesity clinic. Weight, height, waist circumference, blood arterial pressure, lipid profile, glucose, insulin and Tanner stage were measured. BMI, BMI for-age-and sex (BAZ), and HOMA-IR were estimated. HOMA-IR values ≥2.1 and ≥3.3 were considered IR in Tanner I-II, ≥3.3 for Tanner III-IV and ≥2.6 for Tanner V, respectively. Metabolic Syndrome (MetS) was diagnosed with the Cook phenotype. SPISE was estimated according to the following algorithm: [600* HDL^0.185/(TG^0.2* BMI^1.338)]. The optimal SPISE cut points for IR and MetS prediction were determined by ROC curve analysis. Results: In prepubertal obese patients (9.2 ± 2.1y; 18.4% males), the prevalence of IR and MetS was 28.2% y 46.9%, respectively; 58% had severe obesity (BAZ ≥4 SD). In pubertal obese patients (12.6 ± 1.8y; 57% males), the prevalence of IR and MetS was 34.1% and 55.3%, respectively; 34% had severe obesity. In prepubertal children, a SPISE of 6.3 showed the highest sensitivity (73.2%) and specificity (80%) to screen individuals with IR (AUC: 0.80; LR +: 3.3). Likewise, a SPISE of 5.7 got the highest sensitivity (82.6%) and specificity (86.1%) to screen patients with MetS (AUC: 0.87; LR +: 5.4). In pubertal patients, a SPISE of 5.4 showed the highest sensitivity and specificity to screen children and adolescents with both IR (Sn: 76.1%; Sp: 77.5%; AUC: 0.8; LR +: 3.1) and MetS (Sn: 90.4%; Sp: 76.1%; AUC: 0.90; LR +: 3.5). Conclusion: In children and adolescents with obesity, SPISE has good or very good performance in predicting IR and MetS. SPISE may be considered a relatively simple and low-cost diagnosis tool that can be helpful to identify patients with greater biological risk. In adolescents with obesity, the same cut point allows identification of those at higher risk of both IR and MetS.

Iron supplementation given to nonanemic infants: neurocognitive functioning at 16 years.

OBJECTIVE: 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. METHODS: We studied 562 Chilean adolescents (M 16.2 years; 52.7% female) who participated in a randomized controlled iron supplementation trial in infancy. Between 6 and 12 months, 346 consumed an iron-fortified formula (12.7 Fe mg/L) or, if primarily breastfed, liquid vitamins with 15 mg elemental iron as ferrous sulfate, and 216 consumed unmodified cow milk without iron or liquid vitamins without iron if primarily breastfed. RESULTS: 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 (Hb > 100 and < 110 g/L), those who received no-added iron incurred more errors on a visual searching task than those in the iron-supplemented condition. CONCLUSION: 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.Clinical Trials number: NCT01166451.

Iron Deficiency in Infancy and Sluggish Cognitive Tempo and ADHD Symptoms in Childhood and Adolescence.

OBJECTIVE: 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. METHOD: Chilean children (N = 959; 50% male, of Spanish or indigenous descent from working-class backgrounds) were rated by mothers for SCT or AD-HI symptoms at ages 5, 10, and 16 years. Children completed standardized tests assessing verbal and mathematical abilities at ages 5, 10, and 16. At ages 12 and 18 months, children were assessed for iron deficiency. RESULTS: 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. CONCLUSIONS: 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.

Early-life adversity is associated with poor iron status in infancy.

Exposure to early-life adversity (ELA) and iron deficiency early in life are known risk factors for suboptimal brain and socioemotional development. Iron deficiency may arise from and co-occur with ELA, which could negatively affect development. In the present study, we investigated whether ELA is associated with iron deficiency in infants receiving no iron supplementation. This study is a secondary analysis of extant data collected in the 1990s; participants were healthy infants from working-class communities in Santiago, Chile (N = 534, 45.5% female). We measured stressful life events, maternal depression, and low home support for child development during infancy and assessed iron status when the infant was 12 months old. Slightly more than half of the infants were iron-deficient (51%), and 25.8% were iron-deficient anemic at 12 months. Results indicated that ELA was associated with lower iron levels and iron deficiency at 12 months. The findings are consistent with animal and human prenatal models of stress and iron status and provide evidence of the association between postnatal ELA and iron status in humans. The findings also highlight a nutritional pathway by which ELA may impact development and present a nutritionally-focused avenue for future research on ELA and psychopathology.

El Estimador de Sensibilidad Insulínica de Punto Único (SPISE) supera a marcadores antropométricos de uso rutinario en la pesquisa de riesgo cardiometabólico asociado a obesidad: un estudio en adolescentes de la Región Metropolitana / The single Point Insulin Sensitivity Estimator (SPISE) outperforms routine anthropometric markers in the screening of obesity-related cardiometabolic risk: a study in adolescents from the Metropolitan Region

El Estimador de Sensibilidad a la Insulina de Punto Único (SPISE) es un biomarcador de sensibilidad a la insulina comparable al Índice de Matsuda. Se estima utilizando el IMC y los niveles de triglicéridos y HDL. El objetivo de este estudio fue comparar el rendimiento diagnóstico de SPISE con el de otros marcadores antropométricos de uso rutinario, como el IMC y la relación cintura | talla, en la pesquisa de insulinoresistencia (IR) y Síndrome Metabólico (MetS) en una muestra de 901 adolescentes de 11 a 16 años. En todos ellos se midió peso, talla, cintura, presión arterial, perfil lipídico, insulina y glicemia. La IR se diagnosticó con el HOMA-IR y el MetS con el criterio de Cook. Un zIMC ≥2.0 DE, un índice cintura/ talla ≥0.54 y un SPISE ≤ 5.4 fueron los puntos de corte utilizados para evaluar el rendimiento de estos marcadores en el diagnóstico de IR y MetS. No hubo diferencias por sexo en la prevalencia de obesidad, IR y MetS. Tanto en hombre como en mujeres, SPISE mostro una mejor capacidad para predecir el MetS (AUC: 0.95 y 0.89, respectivamente) e IR (AUC: 0.83 y 0.79, respectivamente) comparado con el rendimiento diagnóstico de la relación cintura | talla y el IMC-z. De igual manera, el SPISE mostro una mayor sensibilidad para identificar a los portadores de MetS e IR (96% y 75% en varones y 81% y 67% en mujeres, respectivamente). SPISE mostró una mejor capacidad para identificar el riesgo cardiometabólico asociado a la malnutrición por exceso al compararlo con otros indicadores de uso frecuente en clínica. Un índice de SPISE ≤5.4 fue un mejor predictor de MetS e IR que un IMC ≥2.0 DE y una relación cintura | talla ≥0.54.

The Single Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity comparable to the Matsuda Index. It is estimated using data on BMI, TG, and HDL. We aim to compare the diagnostic performance of SPISE with other routinely used anthropometric markers, such as BMI and waist-to-height ratio, in diagnosing insulin resistance (IR) and Metabolic Syndrome (MetS) in adolescents from 11 to 16 years. Weight, height, waist, blood pressure, lipid profile, insulin, and glycemia were measured. IR was diagnosed with the HOMA-IR and the MetS with the Cook criteria. A BMIz ≥2.0 SD, a waist-to-height ratio ≥0.54, and a SPISE ≤ 5.4 were the cut-off points used for diagnosing IR and MetS. There were no sex differences in the prevalence of obesity, IR, and MetS. In both males and females, SPISE showed a better ability to predict MetS (AUC: 0.95 and 0.89, respectively) and IR (AUC: 0.83 and 0.79, respectively) compared to the waist-to-height ratio and BMI-z. Similarly, SPISE showed greater sensitivity to identify adolescents with MetS and IR (96% and 75% in men and 81% and 67% in women, respectively) than the waist-to-height ratio and BMI-z. SPISE performed better in identifying obesity-related cardiometabolic risk than other frequently used clinical indicators. A SPISE index ≤5.4 was a better predictor of MetS and RI than a BMI ≥2.0 SD and a waist-to-height ratio ≥0.54.

Fasting levels of appetite regulating hormones predict caloric intake at breakfast in a group of Chilean adolescents.

BACKGROUND: 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. AIM: 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. MATERIAL AND METHODS: 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. RESULTS: 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 (ß = -18.65; p < 0.05), whereas leptin, ghrelin and orexin-A levels were positively and independently associated with intake: ß= 5.56, ß = 0.34 and ß = 8.40, respectively, p < 0.05. CONCLUSIONS: 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.

Infant Growth Trajectories and Lipid Levels in Adolescence: Evidence From a Chilean Infancy Cohort.

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.

Association of fasting Orexin-A levels with energy intake at breakfast and subsequent snack in Chilean adolescents.

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.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

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 (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (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.

Association of fasting orexin-A levels with energy intake at breakfast and subsequent snack in Chilean adolescents.

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.

Fasting levels of appetite regulating hormones predict caloric intake at breakfast in a group of Chilean adolescents / Los niveles en ayunas de hormonas reguladoras del apetito predicen la ingesta energética en el desayuno en adolescentes

BACKGROUND: 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. AIM: 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. MATERIAL AND METHODS: 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. RESULTS: 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; p < 0.05), 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, p < 0.05. CONCLUSIONS: 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.

ANTECEDENTES: La regulación del apetito es parte integral de la ingesta alimentaria y es modulada por complejas interacciones entre estímulos internos y externos. Se han caracterizado los mecanismos hormonales que estimulan o inhiben la ingesta, pero los efectos fisiológicos de los niveles séricos de tales hormonas en la regulación del apetito a corto plazo han recibido poca atención. OBJETIVO: Evaluar si los niveles en ayunas de hormonas orexigénicas/ anorexigénicas se asocian con la ingesta energética en el desayuno, entregado inmediatamente después de una muestra de sangre en ayunas, en un grupo de adolescentes. MATERIAL Y MÉTODO: Se efectuaron mediciones antropométricas, composición corporal y medición de niveles en ayunas de leptina, insulina, grelina y orexina-A en 655 adolescentes de 16,8 ± 0,26 años. La ingesta energética se midió en un desayuno semiestandarizado. Se estudiaron las asociaciones entre los niveles hormonales y la ingesta energética mediante modelos lineales multivariados. RESULTADOS: Los valores de leptina, insulina, grelina y orexina-A fueron 7,3 ng/mL, 6,7 UI/dL, 200,8 pg/mL y 16,1 pg/mL respectivamente. Los participantes comieron un promedio de 637 ± 239 calorías en el desayuno. Los niveles de insulina se asociaron inversa e independientemente con la ingesta del desayuno (β = −18,65; p < 0,05), mientras que los niveles de leptina, grelina y orexina-A se asociaron positiva e independientemente con la ingesta: β = 5,65; β = 0,34; β = 8,40, (p < 0,05). CONCLUSIONES: La leptina, grelina y orexina-A en ayunas se asociaron positivamente con la ingesta de energía durante el desayuno proporcionado poco después de la muestra de sangre. La insulina se asoció negativamente con la ingesta de energía. Los factores modificables que influyen en las hormonas reguladoras del apetito podrían ser un objetivo potencial para influir en la ingesta de alimentos.

Adjusting Ferritin Concentrations for Nonclinical Inflammation in Adolescents with Overweight or Obesity.

OBJECTIVE: To compare approaches for adjusting serum ferritin concentrations for inflammation in Chilean adolescents with overweight and obesity. STUDY DESIGN: 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 ferritin <15 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 ferritin <15 µg/L in normal weight individuals without inflammation. Each adjustment approach was compared with this reference prevalence. RESULTS: The sample comprised 61.2% normal weight, 23.7% overweight, and 15.1% obese individuals. The prevalence of inflammation (marked by C-reactive protein level >5.0 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). CONCLUSIONS: 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.

Young adult outcomes associated with lower cognitive functioning in childhood related to iron-fortified formula in infancy.

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 (6-12 m). 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.Clinical Trials number: NCT01166451.

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

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.