Age at puberty and accelerometer-measured physical activity:findings from two independent UK cohorts

Background It is unclear if puberty timing influences future physical activity (PA). Aim To investigate the association of puberty timing with PA across adolescence and adulthood. Subjects and methods Data were from two British cohorts. Participants from an adolescent birth cohort (females = 2349, males = 1720) prospectively reported age at menarche and voice break and had PA recorded by Actigraph accelerometers at ages 14 years and 16 years. A cohort of middle-aged and older adults (40–70 years; females = 48,282; males = 36,112) recalled their age at puberty and had PA (mean acceleration; mg) measured by AxivityAX3 accelerometers. Results After adjustment for age, education, smoking and BMI, per 1-year older age at menarche was associated with higher mean counts/minute at age 14 years (0.07 SD counts/minute; 95% CI = 0.04–0.11) with associations attenuated at age 16 years (0.02; −0.03–0.07). Differences in mean acceleration per older year at menarche were close to the null in women aged 40–49 years (0.02 mg; 0.01–0.03), 50–59 years (0.01; 0.00–0.02) and 60–70 years (0.01; 0.00–0.01). Age at voice break and PA associations were close to the null in both cohorts. Conclusion We found a positive association between puberty timing and PA in females which weakened at older ages and limited evidence of an association at any age in males

Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence

Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers

The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial

Background: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women. Methods: Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m2) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values. Results: All very low-density lipoprotein (VLDL) particles increased by 1.5–3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1–2 SD, between 16 and 36 weeks’ gestation. Triglycerides increased by 2–3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides. Conclusion: There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication. Trial Registration: UPBEAT was registered with Current Controlled Trials, ISRCTN89971375, on July 23, 2008 (prior to recruitment)

Metabolic phenotyping by treatment modality in obese women with gestational diabetes suggests diverse pathophysiology: An exploratory study

Background and purpose: Excess insulin resistance is considered the predominant pathophysiological mechanism in obese women who develop gestational diabetes (GDM). We hypothesised that obese women requiring differing treatment modalities for GDM may have diverse underlying metabolic pathways. Methods: In this secondary analysis of the UK pregnancies Better Eating and Activity Trial (UPBEAT) we studied women from the control arm with complete biochemical data at three gestational time points; at 15–18+6 and 27–28+6 weeks (before treatment), and 34–36+0 weeks (after treatment). A total of 89 analytes were measured (plasma/serum) using a targeted nuclear magnetic resonance (NMR) platform and conventional assays. We used linear regression with appropriate adjustment to model metabolite concentration, stratified by treatment group. Main findings: 300 women (median BMI 35kg/m2; inter quartile range 32.8–38.2) were studied. 71 developed GDM; 28 received dietary treatment only, 20 metformin, and 23 received insulin. Prior to the initiation of treatment, multiple metabolites differed (p<0.05) between the diet and insulin-treated groups, especially very large density lipoprotein (VLDL) and high density lipoprotein (HDL) subclasses and constituents, with some differences maintained at 34–36 weeks’ gestation despite treatment. Gestational lipid profiles of the diet treatment group were indicative of a lower insulin resistance profile, when compared to both insulin-treated women and those without GDM. At 28 weeks’ the diet treatment group had lower plasma fasting glucose and insulin than women treated with insulin, yet similar to those without GDM, consistent with a glycaemic mechanism independent of insulin resistance. Conclusions/Interpretation: This exploratory study suggests that GDM pathophysiological processes may differ amongst obese women who require different treatment modalities to achieve glucose control and can be revealed using metabolic profiling

Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Aβ42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Aβ40, the more prevalent Aβ peptide secreted by cells and a major component of cerebral Aβ deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Aβ42 and Aβ40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.</p> <p>Results</p> <p>Adeno-associated viral (AAV) vectors encoding BRI-Aβ cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Aβ peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Aβ40 and AAV-BRI-Aβ42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Aβ peptides. BRI-Aβ42 and the combination of BRI-Aβ40+42 overexpression resulted in elevated levels of detergent-insoluble Aβ. No significant increase in detergent-insoluble Aβ was seen in the rats expressing APPsw or BRI-Aβ40. No pathological features were noted in any rats, except the AAV-BRI-Aβ42 rats which showed focal, amorphous, Thioflavin-negative Aβ42 deposits.</p> <p>Conclusion</p> <p>The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology <it>in vivo</it>, and demonstrate that whilst expression of Aβ42 alone is sufficient to initiate Aβ deposition, both Aβ40 and Aβ42 may contribute to cognitive deficits.</p

Hospital resource utilization in a national cohort of functionally single ventricle patients undergoing surgical treatment

Objective: To provide a detailed overview of health resource utilization from birth to 18 years old for functionally single ventricle (f-SV) patients and identify associated risk factors./ Methods: All f-SV patients treated between 2000-2017 in England and Wales were linked to hospital and outpatient records using data from the Linking AUdit and National datasets in Congenital HEart Services (LAUNCHES) project. Hospital stay was described in yearly age intervals and associated risk factors were explored using quantile regression./ Results: A total of 3,037 f-SV patients were included, 1409 (46.3%) undergoing a Fontan procedure. During the first year of life the median days spent in-hospital was 60 (IQR 37-102), mostly inpatient days, mirroring a mortality of 22.8%. This decreases to between 2-9 in-hospital days/year afterwards. Between 2-18 years most hospital days were outpatient, with a median of 1-5 days/year./ Lower age at the first procedure, hypoplastic left heart syndrome/mitral atresia, unbalanced atrioventricular septal defect, preterm birth, congenital/acquired comorbidities, additional cardiac risk factors and severity of illness markers were associated with fewer days-at-home and more ICU days in the first year of life. Only markers of early severe illness were associated with fewer days-at-home in the first 6 months post Fontan procedure./ Conclusions: Hospital resource utilization in f-SV is not uniform, decreasing tenfold during adolescence compared to the first year of life. There are subsets of patients with worse outcomes during their first year of life, or with persistently high hospital usage throughout their childhood, which could be the target of future research

Association of parents' and children's physical activity and sedentary time in Year 4 (8-9) and change between Year 1 (5-6) and Year 4:a longitudinal study

Abstract Background Parents could be important influences on child physical activity and parents are often encouraged to be more active with their child. This paper examined the association between parent and child physical activity and sedentary time in a UK cohort of children assessed when the children were in Year 1 (5–6 years old) and in Year 4 (8–9 years old). Methods One thousand two hundred twenty three children and parents provided data in Year 4 and of these 685 participated in Year 1. Children and parents wore an accelerometer for five days including a weekend. Mean minutes of sedentary time and moderate-to-vigorous intensity physical activity (MVPA) were derived. Multiple imputation was used to impute all missing data and create complete datasets. Linear regression models examined whether parent MVPA and sedentary time at Year 4 and at Year 1 predicted child MVPA and sedentary time at Year 4. Change in parent MVPA and sedentary time was used to predict change in child MVPA and sedentary time between Year 1 and Year 4. Results Imputed data showed that at Year 4, female parent sedentary time was associated with child sedentary time (0.13, 95% CI = 0.00 to 0.27 mins/day), with a similar association for male parents (0.15, 95% CI = −0.02 to 0.32 mins/day). Female parent and child MVPA at Year 4 were associated (0.16, 95% CI = 0.08 to 0.23 mins/day) with a smaller association for male parents (0.08, 95% CI = −0.01 to 0.17 mins/day). There was little evidence that either male or female parent MVPA at Year 1 predicted child MVPA at Year 4 with similar associations for sedentary time. There was little evidence that change in parent MVPA or sedentary time predicted change in child MVPA or sedentary time respectively. Conclusions Parents who were more physically active when their child was 8–9 years old had a child who was more active, but the magnitude of association was generally small. There was little evidence that parental activity from three years earlier predicted child activity at age 8–9, or that change in parent activity predicted change in child activity