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OBJECTIVE. The aim of this study was to evaluate whether adaptive responses made to the uterine or very early infant environment are affecting the current metabolic health of young children in the United Kingdom. METHODS. Participants were 300 healthy children and their parents from the EarlyBird Diabetes Study cohort. Children were recruited from randomly selected schools at 5 years of age. Retrospective measures were maternal prepregnancy weight (n = 230), maternal fasting glucose levels at 28 weeks of pregnancy (n = 27), birth weight, and infant weight at ages 3 and 6 weeks. Prospective measures were insulin resistance, height, weight, and percentage of body fat (sum of 5 skinfold measurements) at ages 5, 6, 7, and 8 years. RESULTS. Maternal third-trimester fasting glucose levels were associated positively with birth weight but were not associated with either weight or insulin resistance for the same children at 8 years. Birth weight was unrelated to insulin resistance at 8 years. There were no relationships between weight change in the first weeks of life and weight, percentage of fat, or insulin resistance at 8 years. Longer breastfeeding correlated inversely, although weakly, with percentage of body fat for boys only. Current weight was correlated with insulin resistance at 8 years. CONCLUSIONS. For these contemporary children, neither the gestational environment nor early postnatal growth predicted insulin resistance, which was best predicted by current weight. There was no evidence that predictive adaptive responses made by the fetus or infant affected the child's weight or insulin resistance later in childhood. Key Words birth weight, body composition, body mass index, breasffeeding, children, fetal programming, insulin resistance, metabolic syndrome, obesity, weight Abbreviation HOMA-IR--homeostasis model assessment-insulin resistance, GENETIC SUSCEPTIBILITY TO the metabolic syndrome can have changed little in recent decades, but environmental risk has increased dramatically. The industrialized world is experiencing an epidemic of childhood and adult [...]

Objective. Recent studies of type 2 diabetes in young populations consistently show a predominance of affected girls over boys. Girls are more insulin resistant than boys. We aimed in the present report to establish how much of the sex difference in insulin resistance is intrinsic. Methods. EarlyBird is a community-based, nonintervention cohort study of 307 healthy children from school entry at age 5 years. It asks the question: which children are insulin resistant and why? Anthropometric measures, physical activity, resting energy expenditure, and insulin resistance and its metabolic correlates were measured. Results. At 5 years, insulin resistance was 35% higher in girls than in boys. Girls carried 26% more subcutaneous fat despite similar body weights. However, after correcting for anthropometric variables and physical activity, girls remained 33% more insulin resistant than boys. Triglycerides were significantly higher in girls, and high-density lipoprotein cholesterol and sex hormone--binding globulin were significantly lower. Conclusions. Sex-linked genes may account for the intrinsic sex difference observed. These genes may have an important impact on the development of insulin resistance and the metabolic syndrome and may help b explain the female preponderance of type 2 diabetes in children. Their identification may also help in understanding the pathogenesis of insulin resistance. Pediatrics 2004;113:82-86; type 2 diabetes, insulin resistance, sex difference, programming, sex-linked genes., Type 2 diabetes is becoming a global public health problem. (1) The World Health Organization predicts a rise in prevalence of type 2 diabetes during the 30 years 1995-2025 of [...]

Resting energy expenditure (REE) is reportedly higher in adults with type 2 diabetes and impaired glucose tolerance, and is associated with insulin resistance (IR), independently of obesity. There is less information about these relationships in young children in whom obesity and diabetes are rising. The aim of this analysis was to investigate the relationships between REE, obesity and IR in young children. REE was measured by indirect calorimetry, fat-free mass (FFM) and fat mass (FM) by DEXA, and IR by HOMA in a single cohort of 172 prepubertal children at age 7.0 ± 0.3y. The measurements were repeated at ages 8y and 9y. The fat percentage of girls at 9y was substantially greater than that of boys (26.3% -v- 17.4%, p<0.0). REE was positively associated with FFM and FM at all time-points (all r > 0.32, all p< 0.002). Correlations at 7y and 8y between REE and IR after adjustment for body composition did not reach significance (all r< 0.2, p> 0.07). At age 9y, however, a weak positive correlation emerged between IR and REE independent of body composition in boys but not in girls (boys: r= 0.24, p= 0.01, girls: r= 0.02, p= 0.84) - REE was significantly higher in boys in the highest tertile of IR compared with the lowest tertile of IR, independently of body composition (1456 -v- 1355 kcal/day, p= 0.01). Insulin resistance is believed to limit weight gain. One mechanism may be a rise in REE. The failure of REE to rise with IR in girls, while it does in boys, may help to explain the greater fat percentage of girls at 9y. [ABSTRACT FROM AUTHOR]

Rates of childhood obesity are increasing but few longitudinal studies have examined the contribution of dietary choice. We examined the impact of dietary choice on the development of obesity and insulin resistance in healthy young children from the EarlyBird Study (140 boys, 111 girls). The following measures were made annually from 5 to 9 years: BMI(sds), sum of 5 skinfolds (SSF), fasting glucose and insulin to calculate insulin resistance (HOMAIR); % abdominal fat by Dexa at 9y. Food frequency questionnaires were completed annually by a parent and three variables calculated (number of days consumed per week expressed as a percentage of maximum possible frequency): HS (composite of 6 high sugar foods and drinks including cola), HF (11 high fat foods), FV (3 foods: fruit, vegetables, salad). No food was assigned to more than one group. 1. Dietary reports were consistent year-on-year (in each food group year-on-year correlation r=0.3-0.5, p<0.001). 2. From 5-9 years, BMI(sds) rose (0.34 to 0.48, p=0.007); SSF rose (3.98cm to 5.62cm, p<0.001) yet frequency of HF fell (25.5% to 22.1%, p<0.001) and HS fell 54.4% to 49.3%, p<0.001). 3. Frequency of FV remained unchanged (11.4% to 11.6%, p=0.5) and was not associated with BMI or SSF in either gender, or with HOMA-IR in boys (r<0.1). In girls at 5y and 6y, FV was positively associated with HOMA-IR (r=0.21, 0.22, p<0.05). 4. Frequency of HF correlated with HS foods at each age (r=0.2-0.6, p<0.01). 5. BMI at 8 and 9y was inversely related to HF in both genders (r=-0.18 to -0.28, p<0.05). 6. BMI and SSF were inversely related to HS at every age, significantly so in girls (r= -0.18 to -0.29, p<0.05). 7. HS at 5y predicted lower BMI, SSF, HOMA-IR and % abdominal fat at 9y in girls (r=-0.26, -0.30, -0.24, -0.26, p<0.05 respectively). Parental reports regarding children's dietary habits are consistent year-on-year. Body size appears unrelated to frequency of consumption of healthy foods. Unexpectedly, children whose diets are highest in fat and sugar seem to be the leanest and metabolically healthiest. This could be due to parental misreporting, but it is also possible that meal size is more important than content in childhood obesity. [ABSTRACT FROM AUTHOR]

In adults, physical activity (PA) has been shown to lower insulin resistance (IR) but to have no impact on adiponectin. Little is known of these associations in children. In this report we explore the relationships between PA and cardio-diabetic markers in young children. MTI accelerometers were used to obtain objective measures of long-term, habitual PA in a cohort of healthy, prepubertal children, recruited at age 5±0.3y. Seven-day PA recordings were taken and averaged over four annual time points (at 5, 6, 7 & 8y). Other outcome measures reported here are adiponectin, insulin resistance (HOMA-IR), leptin and high sensitivity C-reactive protein (hsCRP) at 8y. Potential confounders (age, total body fat % by DEXA and waist circumference at 8y) were controlled for in the analysis. The following results are based on 112 boys and 90 girls for whom a complete data set was available. Adiponectin was found to be inversely associated with PA in girls (R² change from the adjusted model: 8%, p=0.01). Indeed, adiponectin was almost 40% higher in the least active tertile compared With the most active tertile (effect size: 1.02SD, p=0.003). However, no such association was found in boys (R² change: 1%, p=0.33). There were no independent associations in either sex between PA and HOMA-IR (both R² change: <2%, p>0.18), PA and leptin (both R² change: 0%, p>0.60) or PA and hsCRP (both R² change: <2%, p>0.20). Whereas in adults physical activity appears to lower insulin resistance but not adiponectin, the opposite would seem to be the case in young children. Physical activity, at least in girls, is associated with lower adiponectin levels but not lower insulin resistance. These unexpected age and gender differences suggest that the role and regulation of such cardio-diabetic markers is more complex in children than in adults. By following this cohort annually into early adulthood, we will be in position to track these associations as they evolve. [ABSTRACT FROM AUTHOR]

Interventions to promote healthier lifestyles and reduce diabetes risk increasingly target lower socio-economic groups. The belief is that those living in the most deprived neighbourhoods are most at risk of inactivity, obesity and metabolic disturbance. We tested this assumption in a prospective cohort of 224 healthy children (125 boys) attending 53 primary schools representing a wide socio-economic range. Home deprivation was assessed by a multiple deprivation index using individual home postcode and school deprivation by the percentage of pupils entitled to free lunch at the school attended. Physical activity (PA) was monitored objectively by accelerometry, and the mean of 4 recordings, each over 7 days, at ages 5, 6, 7 and 8 was used to estimate the child's habitual PA. Body mass index sds (BMI) was measured at 8y. Metabolic risk (MET-risk) was assessed at 8y using the mean z-score of four markers: insulin resistance (HOMA), triglycerides, cholesterol/HDL ratio and blood pressure. In boys, PA was not significantly different in those living in deprived areas (r= 0.14, p=0.13) and unexpectedly higher in the more deprived schools (r= 0.26, p=0.004). Neither index of deprivation was significantly related to BMI (home r= -0.16, p=0.07; school r= -0.04, p=0.64). Similarly, deprivation was not associated with MET-risk, even adjusting for BMI (home r= -0.01, p=0.94; school r= -0.04, p=0.66). MET-risk was, however, weakly related to habitual PA (r= -0.17, p=0.05). In girls, neither index of deprivation was related to PA (both r<0.05, p>0.66), or to BMI (both r<0.08, p>0.43) or to MET-risk (both r< +/0.04, p>0.70, even adjusting for BMI). MET-risk was unrelated to PA (r= -0.10, p=0.35). Crucially, MET-risk, even at this young age, was closely related to BMI in both girls and boys (r=0.47 and 0.50 repectively, both p<0.001). In conclusion we could find no evidence, in contemporary children, that diabetes risk is associated with socio-economic deprivation. Excess weight gain appears to be the overriding factor, irrespective of social status. These findings may have important economic implications in health care targeting. [ABSTRACT FROM AUTHOR]

Objective: An HbA1c threshold of ≥ 6.5% has recently been adopted for the diagnosis of diabetes in adults, and of ≥ 5.7% to identify adults at risk. Little,however, is known of HbA1c's behaviour or diagnostic value in youth. Our aim was to describe the course of HbA1c during childhood, and its association with fasting glucose., Research Design and Methods: HbA1c and glucose were measured every year in a cohort of 326 healthy children (162 boys) from 5 to 15 years. Mixed effects modelling was used to establish the determinants of HbA1c and its development over time. ROC analysis was used to determine the diagnostic value of HbA1c in the 55 individuals who showed impaired fasting glucose(IFG – glucose ≥ 5.6 mmol/L)., Results: Glucose rose progressively from 4.3 mmol/L at 5 years to 5.1 mmol/Lat 15 years, and although there were positive associations between HbA1c and glucose, from 10 to 13 years, HbA1c fell while glucose continued to rise. IFG developed in 55 children, but HbA1c exceeded 5.7% in only 16 of them. The maximum area under the ROC curve was 0.71 at the age of 14 (p<0.001), and the sensitivity and specificity were optimal at 50 and 80% respectively,corresponding to HbA1c of 5.4%., Conclusions: Although HbA1c retains a positive association with glucose throughout childhood, it is weak, and their trends diverge from 10 years,suggesting that factors other than glycaemia systematically influence the variance of HbA1c in youth. These findings therefore limit the interpretation of HbA1c for the diagnosis of IFG during childhood.