Exercise to preserve ß-cell function in recent-onset Type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial.

AIM: Residual ß-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this ß-cell function reduces complications. We hypothesized that exercise preserves ß-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: A randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of ß-cell function between intervention and control at 6 and 12 months. RESULTS: Of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of ß-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of ß-cell function. (Clinical Trials Registry No; ISRCTN91388505).

Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71).

BACKGROUND: Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. METHODS: In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. RESULTS: Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (s.d.±4m) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. CONCLUSIONS: There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment.

Childhood obesity: evidence for distinct early and late environmental determinants a 12-year longitudinal cohort study (EarlyBird 62).

BACKGROUND/OBJECTIVE: The prevalence of childhood obesity continues to rise in most countries, but the exposures responsible remain unclear. The shape of the body mass index (BMI) distribution curve defines how a population responds, and can be described by its three parameters-skew (L), median (M) and variance (S). We used LMS analysis to explore differences in the BMI trajectories of contemporary UK children with those of 25 years ago, and to draw inferences on the exposures responsible. SUBJECTS/METHODS: We applied Cole's LMS method to compare the BMI trajectories of 307 UK children (EarlyBird cohort) measured annually from 5-16 years (2000-2012) with those of the BMI data set used to construct the UK 1990 growth centiles, and used group-based trajectory modelling (GBTM) to establish whether categorical trajectories emerged. RESULTS: Gender-specific birth weights were normally distributed and similar between both data sets. The skew and variance established by 5 years in the 1990 children remained stable during the remainder of their childhood, but the pattern was different for children 25 years on. The skew at 5 years among the EarlyBird children was greatly exaggerated, and involved selectively the offspring of obese parents, but returned to 1990 levels by puberty. As the skew diminished, so the variance in BMI rose sharply. The median BMI of the EarlyBird children differed little from that of 1990 before puberty, but diverged from it as the variance rose. GBTM uncovered four groups with distinct trajectories, which were related to parental obesity. CONCLUSIONS: There appear to be two distinct environmental interactions with body mass among contemporary children, the one operating selectively according to parental BMI during early childhood, the second more generally in puberty.

Awareness of body weight by mothers and their children: repeated measures in a single cohort (EarlyBird 64).

BACKGROUND: Mothers often do not realize when their child is overweight. We aimed to compare mothers' perceptions of children's weight before and during puberty, and to explore factors at 7 years predicting recognition of overweight at 16 years. METHODS: Mothers of 237 children (136 boys) from the EarlyBird study estimated their own weight category and that of their child aged 7 years and 16 years. The children estimated their own weight category at 16 years. Annual measures: body mass index standard deviation score (BMIsds), per cent fat, physical activity. Pubertal development assessed by age at peak height velocity (APHV). MATERNAL MEASURES: BMI, education, socio-economic status. RESULTS: At 7 years 21% of girls and 16% of boys were overweight or obese, rising to 27% and 22% respectively at 16 years. The accuracy of the mother's perception of her child's weight category improved from 44% at 7 years to 74% at 16 years, but they were less able to judge overweight in sons than daughters. The mothers' level of concern about overweight was greater for girls than boys, and increased for girls (52% mothers of overweight/obese girls were worried at 7 years, 62% at 16 years), but remained static in the boys (42% vs. 39%). Over 80% of the youngsters realized when they were overweight, but 25% normal-weight girls also classed themselves as overweight. Only BMI predicted a mother's ability to correctly perceive her child's weight. Neither her awareness, nor concern, about the child's weight at 7 years had any impact on the trajectory of the child's BMI from 7 years to 16 years. CONCLUSIONS: Parents are central to any successful weight reduction programme in their children, but will not engage while they remain ignorant of the problem. Crucially, any concern mothers may have about their child's excess weight at 7 years appears to have no impact on subsequent weight change.

Gender-assortative waist circumference in mother-daughter and father-son pairs, and its implications. An 11-year longitudinal study in children (EarlyBird 59).

BACKGROUND/OBJECTIVES: Body mass index (BMI) is reportedly gender assortative (mother-daughter, father-son) in contemporary children. We investigated the corresponding transmission of waist circumference (WC) and its implications. METHODS: We measured parental WC at baseline and WC, height, weight and para-umbilical skin-fold (USF) annually in their offspring from 5 to 15 years (n = 223 trios). Parents were deemed normal metabolic risk (NR) or high risk (HR) according to World Health Organization (WHO) cut-points for WC (mothers 80 cm, fathers 94 cm). The residual from WC adjusted for BMI (WC|BMI ) was used as a surrogate for excess intra-abdominal fat, and its association with insulin resistance (HOMA2-IR) was sought. RESULTS: WC and USF were both gender assortative, while WC|BMI was not. WC was greater by 1.62 cm (P < 0.05, confidence interval [CI]: 0.09-3.16) and USF by 0.37 cm (P < 0.01, CI: 0.19-0.56) among the daughters (but not the sons) of HR compared with those of NR mothers, and by 1.32 cm (P < 0.05, CI: 0.09-2.55) and 0.18 cm (P < 0.05, CI: 0.04-0.32), respectively in the corresponding father-son (but not father-daughter) pairings. No such differences could be demonstrated for WC|BMI . A standard deviation score 1(SDS) change in WC|BMI , independent of BMI, was associated with a 7.14% change in IR in girls (P < 0.01, CI: 1.76-12.80) and 8.02% in boys (P < 0.001, CI: 2.93-13.36), but there was no relationship between IR and USF. CONCLUSION: The relationship of offspring WC to metabolic health and to parental size is complex. Subcutaneous abdominal fat is gender assortative but harmless, while intra-abdominal fat (its surrogate in this analysis) is unrelated to parental waist circumference, but metabolically harmful.