Joanne Hosking

Contribution of Early Weight Gain to Childhood Overweight and Metabolic Health: A Longitudinal Study (EarlyBird 36)

BACKGROUND. Early weight gain (0–5 years) is thought to be an important contributor to childhood obesity and consequently metabolic risk. There is a scarcity of longitudinal studies in contemporary children reporting the impact of early weight gain on metabolic health. OBJECTIVE. We aimed to assess the impact of early weight gain on metabolic health at 9 years of age. METHOD. Two hundred thirty-three children (134 boys, 99 girls) with a gestational age of >37 weeks were assessed at birth, 5 years of age, and 9 years of age. Measures included weight SD scores at each time point and excess weight gained (Δ weight SD score) between them. The outcome measure included composite metabolic score (sum of internally derived z scores of insulin resistance, mean blood pressure, triglyceride level, and total cholesterol/high-density lipoprotein cholesterol ratio). RESULTS. Weight SD score increased by 0.29 SD score in girls and 0.26 SD score in boys from 0 to 5 years of age and by 0.03 SD score in girls and 0.11 SD score in boys from 5 to 9 years of age. Weight SD score correlated poorly to moderately before 5 years of age but strongly after 5 years of age. Birth weight SD score predicted (girls/boys) 2.4%/0% of the variability in composite metabolic score at 9 years of age. Adding Δ weight SD score (0–5 years old) contributed (girls/boys) 11.2%/7.0% to the score, and adding Δ weight SD score (5–9 years old) additionally contributed (girls/boys) 26.4%/16.5%. Importantly, once weight SD score at 9 years of age was known, predictive strength was changed little by adding Δ weight SD score. CONCLUSIONS. Most excess weight before puberty is gained before 5 years of age. Weight at 5 years of age bears little relation to birth weight but closely predicts weight at 9 years of age. Single measures of current weight are predictive of metabolic health, whereas weight gain within a specific period adds little. A single measure of weight at 5 years of age provides a pointer to future health for the individual. If metabolic status at 9 years of age means future risk, diabetes/cardiovascular prevention strategies might better focus on preschool-aged children, because the die seems to be largely cast by 5 years of age, and a healthy weight early in childhood may be maintained at least into puberty.

Fatness leads to inactivity, but inactivity does not lead to fatness: a longitudinal study in children (EarlyBird 45)

Objective To establish in children whether inactivity is the cause of fatness or fatness the cause of inactivity. Design A non-intervention prospective cohort study examining children annually from 7 to 10 years. Baseline versus change to follow-up associations were used to examine the direction of causality. Setting Plymouth, England. Participants 202 children (53% boys, 25% overweight/obese) recruited from 40 Plymouth primary schools as part of the EarlyBird study. Main outcome measures Physical activity (PA) was measured using Actigraph accelerometers. The children wore the accelerometers for 7 consecutive days at each annual time point. Two components of PA were analysed: the total volume of PA and the time spent at moderate and vigorous intensities. Body fat per cent (BF%) was measured annually by dual energy x ray absorptiometry. Results BF% was predictive of changes in PA over the following 3 years, but PA levels were not predictive of subsequent changes in BF% over the same follow-up period. Accordingly, a 10% higher BF% at age 7 years predicted a relative decrease in daily moderate and vigorous intensities of 4 min from age 7 to 10 years (r=−0.17, p=0.02), yet more PA at 7 years did not predict a relative decrease in BF% between 7 and 10 years (r=−0.01, p=0.8). Conclusions Physical inactivity appears to be the result of fatness rather than its cause. This reverse causality may explain why attempts to tackle childhood obesity by promoting PA have been largely unsuccessful.

Physical activity at the government-recommended level and obesity-related health outcomes: a longitudinal study (Early Bird 37)

Background: In the UK and USA, government guidelines for childhood physical activity have been set (⩾60 min/day at ⩾3 metabolic equivalents of thermogenesis (METs)), and body mass index (BMI) chosen as the outcome measure. Aim: To determine the extent to which physical activity at the government-recommended intensity is associated with change in body mass/fat and metabolic health in pre-pubertal children. Methods: Non-intervention longitudinal study of 113 boys and 99 girls (born 1995/96) recruited from 54 schools. Physical activity (Actigraph accelerometers), changes in body mass (raw and age/gender-standardised BMI), fatness (skin-fold thickness and waist circumference) and metabolic status (insulin resistance, triglycerides, cholesterol/HDL ratio and blood pressure – separately and as a composite metabolic z score) were measured on four annual occasions (5, 6, 7 and 8 years). Results: Mean physical activity did not change over time in either sex. Averaging the 7-day recordings from four time points rather than one increased the reliability of characterising a child’s activity from 71% to 90%. Some 42% of boys and 11% of girls met the guideline. There were no associations between physical activity and changes in any measurement of body mass or fatness over time in either sex (eg, BMI standard deviation scores: r = −0.02, p = 0.76). However, there was a small to moderate inverse association between physical activity and change in composite metabolic score (r = −0.19, p<0.01). Mixed effects modelling showed that the improvement in metabolic score among the more active compared to the less active children was linear with time (−0.08 z scores/year, p = 0.001). Conclusions: In children, physical activity above the government-recommended intensity of 3 METs is associated with a progressive improvement in metabolic health but not with a change in BMI or fatness. Girls habitually undertake less physical activity than boys, questioning whether girls in particular should be encouraged to do more, or the recommendations adjusted for girls.

Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty: A 9-year longitudinal study (EarlyBird 26)

OBJECTIVE Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5–14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L). RESULTS IR rose progressively from age 7 years, 3–4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels. CONCLUSIONS IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.

The impact of school-time activity on total physical activity: the activitystat hypothesis (EarlyBird 46).

Objectives:To explore the activitystat hypothesis in primary school children by asking whether more physical activity (PA) in school time is compensated for by less PA at other times.Study Design:Observational, repeated measures (four consecutive occasions over a 12-month period).Setting:South-west England.Participants:A total of 206 children (115 boys, aged 8–10 years) from 3 primary schools (S1, S2 and S3), which recorded large differences in PA during school time.Measurements:Total PA (TPA) and its moderate-and-vigorous component were recorded weekly by accelerometry, in school and out of school, and adjusted for local daily rainfall and daylight hours. Habitual PA was assessed by linear mixed-effects modelling on repeated measures.Results:S1 children recorded 64% more in-school PA, but S2 and S3 children compensated with correspondingly more out-of-school PA, so that TPA between the three schools was no different: 35.6 (34.3–36.9), 37.3 (36.0–38.6) and 36.2 (34.9–37.5)  Units, respectively (P=0.38).Conclusions:The PA of children seems to compensate in such a way that more activity at one time is met with less activity at another. The failure of PA programmes to reduce childhood obesity could be attributable to this compensation.

Adiponectin in childhood

Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectins role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear.

Validation of foot-to-foot bioelectrical impedance analysis with dual-energy X-ray absorptiometry in the assessment of body composition in young children: the EarlyBird cohort

Foot-to-foot bioelectrical impedance analysis (BIA) is simple and non-invasive, making it particularly suitable for use in children. There is insufficient evidence of the validity of foot-to-foot BIA compared with dual-energy X-ray absorptiometry (DEXA) as the criterion method in healthy young children. Our objective was to assess the validity of foot-to-foot BIA against DEXA in a large cohort of healthy young children. Body composition was measured by foot-to-foot BIA and DEXA in 203 children (mean age 8.9 (SD 0.3) years). Bland-Altman and simple linear regression analyses were used to determine agreement between methods. BIA overestimated fat-free mass by a mean of 2.4% in boys and 5.7% in girls, while fat mass was underestimated by 6.5% in boys and 10.3% in girls. The percentage fat recorded by BIA was, accordingly, also lower than by DEXA (boys 4.8%; girls 12.8%). In boys, however, there were correlations between the size of the difference between methods and the size of the measure under consideration such that in smaller boys fat-free mass was underestimated (r-0.57; P<0.001) while fat mass and percentage fat were overestimated (r 0.74 for fat mass; r 0.69 for percentage fat; both P<0.001) with the reverse in bigger boys. Mean differences between techniques were greater in the girls than in the boys but in boys only, the direction of the differences was dependent upon the size of the child. Therefore, BIA may be useful for large-scale studies but is not interchangeable with DEXA and should be interpreted with caution in individuals.

PGC1α Promoter Methylation in Blood at 5–7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)

The early environment, acting via epigenetic processes, is associated with differential risk of cardiometabolic disease (CMD), which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analyzed DNA methylation in the peroxisome proliferator–activated receptor γ coactivator 1α promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years of age by pyrosequencing. Body composition was measured annually by dual X-ray absorptiometry, physical activity by accelerometry, and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven cytosine guanine dinucleotide (CpG) loci were identified that showed no significant temporal change or association with leukocyte populations. Modeling using generalized estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing, and activity. Methylation of one predictive locus modified binding of the proadipogenic pre–B-cell leukemia homeobox-1/homeobox 9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.

Objectively measured physical activity and its association with adiponectin and other novel metabolic markers: a longitudinal study in children (EarlyBird 38).

OBJECTIVE—Recent evidence suggests that, in children, traditional markers of metabolic disturbance are related only weakly to physical activity. We therefore sought to establish the corresponding relationships with newer metabolic markers. RESEARCH DESIGN AND METHODS—This was a nonintervention longitudinal study of 213 healthy children recruited from 54 schools in Plymouth, U.K. MTI accelerometers were used to make objective 7-day recordings of physical activity at ages 5 ± 0.3 (mean ± SD), 6, 7, and 8 years. Overall physical activity was taken as the average of the four annual time points. The metabolic markers at 8 years were adiponectin, leptin, high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment). Potential confounders included percent body fat measured by dual-energy X-ray absorptiometry and diet measured by food frequency questionnaire. RESULTS—Whereas physical activity did not correlate with insulin resistance (r = −0.01), leptin (r = +0.04), or hsCRP (r = +0.01) independently of percent body fat, it did correlate with adiponectin, but inversely (r = −0.18, P = 0.02). This unexpected inverse relationship was strongest among the less active children (physical activity < median: r = −0.30, P = 0.01) but negligible in the more active children (physical activity > median: r = +0.04, P = 0.76). Adiponectin was significantly higher (0.52 SD, P < 0.01) in the least active tertile compared with the other two tertiles. Insulin resistance, however, did not differ across the physical activity tertiles (P = 0.62). CONCLUSIONS—Adiponectin levels in children are highest among those who are least active, but their insulin resistance is no different. Adiponectin has a known insulin-sensitizing effect, and our findings are consistent with a selective effect at low levels of physical activity.

BMI was right all along: taller children really are fatter (implications of making childhood BMI independent of height) EarlyBird 48.

Objective:Several studies suggest that taller children may be wrongly labelled as ‘overweight’ because body mass index (BMI) is not independent of height (Ht) in childhood, and recommend adjustment to render the index Ht independent. We used objective measures of %body fat and hormonal/metabolic markers of fatness to investigate whether BMI and the corresponding fat mass index (FMI) mislead in childhood, or whether taller children really are fatter.Design:Longitudinal observational study measuring children annually from age 7 to 12 years.Subjects:Two hundred and eighty healthy children (56% boys) from the EarlyBird study.Measurements:BMI (body mass (BM)/Ht2), FMI (fat mass (FM)/Ht2), %body fat ((FM/BM) × 100, where FM was measured by dual-energy X-ray absorptiometry), fasting leptin (a hormonal measure of body fatness) and insulin resistance (a metabolic marker derived from the validated homeostasis model assessment program for insulin resistance - HOMA2-IR) were all analysed in relation to Ht. Alternative Ht-independent indices of BM and FM were compared with BMI and FMI as indicators of true fatness and related health risk.Results:BMI and FMI correlated with Ht at each annual time point (r∼0.47 and 0.46, respectively), yet these correlations were similar in strength to those between Ht and %fat (r∼0.47), leptin (r∼0.41) and insulin resistance (r∼0.40). Also, children who grew the most between 7 and 12 years showed greater increases in BMI, FMI, leptin and insulin resistance (tertile 1 vs 3, all p<0.05). BMI and FMI explained ∼20% more of the variation in %fat, ∼15% more in leptin and ∼10% more in insulin resistance than the respective Ht-independent reformulations (BM/Ht3.5 and FM/Ht7, both p<0.001).Conclusion:Taller children really are fatter than their shorter peers, have higher leptin levels and are more insulin resistant. Attempts to render indices of BM or FM independent of Ht in children seem inappropriate if the object of the index is to convey health risk.