Long-term vs. recent-onset obesity: their contribution to cardiometabolic risk in adolescence.
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SUBMITTER: Burrows R
PROVIDER: S-EPMC6891158 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Long-term vs. recent-onset obesity: their contribution to cardiometabolic risk in adolescence.
Burrows Raquel R Correa-Burrows Paulina P Rogan José J Cheng Evaline E Blanco Estela E Gahagan Sheila S
Pediatric research 20190819 6
<h4>Background</h4>The contribution of long-term vs. recent-onset obesity to cardiometabolic risk in adolescence remains controversial. Here, we aimed to investigate the association of time of onset and length of obesity with the cardiometabolic profile of adolescence.<h4>Methods</h4>Prospective study in 678 16-year-olds. BMI was measured at birth-1-5-10-16 years and BMI trajectories were interpolated using cubic splines. BMI > 2 SD at <6 years was defined as early obesity. Waist circumference ( ...[more]
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Project description:Aims/hypothesisMucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes expressing an αβ T cell antigen receptor that recognises the MHC-related 1 molecule. MAIT cells are altered in children at risk for and with type 1 diabetes, and mouse model studies have shown MAIT cell involvement in type 1 diabetes development. Since several studies support heterogeneity in type 1 diabetes physiopathology according to the age of individuals, we investigated whether MAIT cells were altered in adults with type 1 diabetes.MethodsMAIT cell frequency, phenotype and function were analysed by flow cytometry, using fresh peripheral blood from 21 adults with recent-onset type 1 diabetes (2-14 days after disease onset) and 47 adults with long-term disease (>2 years after diagnosis) compared with 55 healthy blood donors. We also separately analysed 17 women with long-term type 1 diabetes and an associated autoimmune disease, compared with 30 healthy women and 27 women with long-term type 1 diabetes.ResultsMAIT cells from adults with recent-onset type 1 diabetes, compared with healthy adult donors, harboured a strongly activated phenotype indicated by an elevated CD25+ MAIT cell frequency. In adults with long-term type 1 diabetes, MAIT cells displayed an activated and exhausted phenotype characterised by high CD25 and programmed cell death 1 (PD1) expression and a decreased production of proinflammatory cytokines, IL-2, IFN-γ and TNF-α. Even though MAIT cells from these patients showed upregulated IL-17 and IL-4 production, the polyfunctionality of MAIT cells was decreased (median 4.8 vs 13.14% of MAIT cells, p < 0.001) and the frequency of MAIT cells producing none of the effector molecules analysed increased (median 34.40 vs 19.30% of MAIT cells, p < 0.01). Several MAIT cell variables correlated with HbA1c level and more particularly in patients with recent-onset type 1 diabetes. In women with long-term type 1 diabetes, MAIT cell alterations were more pronounced in those with an associated autoimmune disease than in those without another autoimmune disease. In women with long-term type 1 diabetes and an associated autoimmune disease, there was an increase in CD69 expression and a decrease in the survival B-cell lymphoma 2 (BCL-2) (p < 0.05) and CD127 (IL-7R) (p < 0.01) marker expression compared with women without a concomitant autoimmune disorder. Concerning effector molecules, TNF-α and granzyme B production by MAIT cells was decreased.Conclusions/interpretationAlterations in MAIT cell frequency, phenotype and function were more pronounced in adults with long-term type 1 diabetes compared with adults with recent-onset type 1 diabetes. There were several correlations between MAIT cell variables and clinical characteristics. Moreover, the presence of another autoimmune disease in women with long-term type 1 diabetes further exacerbated MAIT cell alterations. Our results suggest that MAIT cell alterations in adults with type 1 diabetes could be associated with two aspects of the disease: impaired glucose homeostasis; and autoimmunity.
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Project description:Background and objectiveThere is a paucity of prospective evidence examining the links between sedentary time (ST) and cardiometabolic outcomes in youth. We examined the associations between objectively assessed ST and moderate to vigorous physical activity (MVPA) in childhood with cardiometabolic risk in adolescence.MethodsThe study included 4639 children (47% male) aged 11 to 12 years at baseline whose mothers were enrolled in ALSPAC (Avon Longitudinal Study of Parents and Children) during their pregnancy in the early 1990s. A total of 2963 children had valid blood samples at age 15 to 16 years. Associations with baseline ST and MVPA were examined for BMI, waist circumference, body fat mass, lean body mass, systolic and diastolic blood pressure, fasting triglycerides, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, glucose, insulin, C-reactive protein, and a clustered standardized cardiometabolic risk score (CMscore).ResultsBaseline ST was not associated deleteriously with any cardiometabolic markers. MVPA was beneficially associated with the 3 adiposity indicators, lean body mass, systolic blood pressure, triglycerides, C-reactive protein, insulin, HDL cholesterol, and CMscore; once the models were adjusted for baseline levels of these markers, these associations remained for body fat mass (mean difference per 10 minutes of MVPA: -0.320 [95% confidence interval (CI): -0.438 to -0.203]; P < .001), HDL cholesterol (0.006 logged mmol/L [95% CI: 0.001 to 0.011]; P = .028), insulin (-0.024 logged IU/L [95% CI: -0.036 to -0.013]; P < .001), and CMscore (-0.014 [95% CI: -0.025 to -0.004]; P = .009).ConclusionsWe found no evidence linking ST in late childhood with adverse cardiometabolic outcomes in adolescence. Baseline MVPA was beneficially linked to broad cardiometabolic health in adolescence.
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Project description:BACKGROUND:Body mass index of living kidney donors has increased substantially. Determining candidacy for live kidney donation among obese individuals is challenging because many donation-related risks among this subgroup remain unquantified, including even basic postdonation mortality. METHODS:We used data from the Scientific Registry of Transplant Recipients linked to data from the Centers for Medicare and Medicaid Services to study long-term mortality risk associated with being obese at the time of kidney donation among 119,769 live kidney donors (1987-2013). Donors were followed for a maximum of 20 years (interquartile range 6.0-16.0). Cox proportional hazards estimated the risk of postdonation mortality by obesity status at donation. Multiple imputation accounted for missing obesity data. RESULTS:Obese (body mass index ? 30) living kidney donors were more likely male, African American, and had higher blood pressure. The estimated risk of mortality 20 years after donation was 304.3/10,000 for obese and 208.9/10,000 for nonobese living kidney donors. Adjusting for age, sex, race/ethnicity, blood pressure, baseline estimated glomerular filtration rate, relationship to recipient, smoking, and year of donation, obese living kidney donors had a 30% increased risk of long-term mortality compared with their nonobese counterparts (adjusted hazard ratio: 1.32, 95% CI: 1.09-1.60, P = .006). The impact of obesity on mortality risk did not differ significantly by sex, race or ethnicity, biologic relationship, baseline estimated glomerular filtration rate, or among donors who did and did not develop postdonation kidney failure. CONCLUSION:These findings may help to inform selection criteria and discussions with obese persons considering living kidney donation.
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Project description:ImportanceThe American Academy of Pediatrics currently recommends weight for length (WFL) for assessment of weight status in children younger than 2 years but body mass index (BMI) for children older than 2 years. However, the clinical implications of using WFL vs BMI in children younger than 2 years as an indicator of future health outcomes remains understudied.ObjectiveTo compare associations of overweight based on WFL vs BMI in children younger than 2 years with cardiometabolic outcomes during early adolescence.Design, setting, and participantsThis prospective study of birth cohorts in the United States (Project Viva) and Belarus (Promotion of Breastfeeding Intervention Trial [PROBIT]) performed from June 1, 1996, to November 31, 2002, included 13 666 children younger than 2 years.Main exposuresOverweight defined as Centers for Disease Control and Prevention (CDC) WFL in the 95th percentile or greater, World Health Organization (WHO) WFL in the 97.7th percentile or greater, or WHO BMI in the 97.7th percentile or greater at 6, 12, 18, or 24 months of age.Main outcomes and measuresPrimary outcomes were fat mass index, insulin resistance, metabolic risk score, and obesity during early adolescence. Secondary outcomes were height and BMI z scores, sum of skinfolds, waist circumference, and systolic blood pressure during early adolescence.ResultsThe study included 919 children (mean [SD] age, 12.9 [0.9] years; 460 [50.1%] male; and 598 [65.1%] white) from Project Viva and 12 747 children (mean [SD] age, 11.5 [0.5] years; 6204 [48.7%] male; and 12 747 [100%] white) from PROBIT. During 6 to 24 months of age, in Project Viva, 206 children (22.4%) were overweight at any of the 4 times points according to the CDC WFL, 160 (17.4%) according to WHO WFL, and 161 (17.5%) according to WHO BMI cut points. In PROBIT, 3715 children (29.1%) were overweight at any of the 4 time points according to the CDC WFL, 3069 (24.1%) according to WHO WFL, and 3125 (24.5%) according to WHO BMI cut points. After maternal and child characteristics were adjusted for, being ever overweight (vs never overweight) during 6 to 24 months of age was associated with higher likelihood of adverse cardiometabolic risk markers during early adolescence, but associations did not differ substantially across WFL and BMI cut points in either cohort. For example, for fat mass index in Project Viva, β = 0.9 (95% CI, 0.5-1.4) for the CDC WFL, β = 1.1 (95% CI, 0.6-1.6) for WHO WFL, and β = 1.4 (95% CI, 0.9-1.9) for WHO BMI. For PROBIT, β = 0.5 (95% CI, 0.4-0.6) for the CDC WFL, β = 0.6 (95% CI, 0.5-0.7) for WHO WFL, and β = 0.6 (95% CI, 0.5-0.6) for WHO BMI. Neither growth metric in infancy was superior over the others based on F statistics (Project Viva: 17.1-17.8; PROBIT: 87.1-88.7). Findings were similar for insulin resistance, metabolic risk score, obesity, and secondary outcomes.Conclusions and relevanceChoice of WFL vs BMI to define overweight during the first 2 years of life may not greatly affect the association with cardiometabolic outcomes during early adolescence. The findings appear to have important implications for investigators seeking to use BMI as a growth metric for epidemiologic research and for practitioners monitoring the weight status of children younger than 2 years.
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Project description:Importance:Inadequate sleep duration and quality increase the risk of obesity. Sleep timing, while less studied, is important in adolescents because increasing evening preferences (chronotypes), early school start times, and irregular sleep schedules may cause circadian misalignment. Objective:To investigate associations of chronotype and social jet lag with adiposity and cardiometabolic risk in young adolescents. Design, Setting, and Participants:Starting in 1999, Project Viva recruited pregnant women from eastern Massachusetts. Mother-child in-person visits occurred throughout childhood. From January 23, 2012, to October 16, 2016, 804 adolescents aged 12 to 17 years completed 5 days or more of wrist actigraphy, questionnaires, and anthropometric measurements. A cross-sectional analysis using these data was conducted from April 31, 2018, to May 1, 2019. Exposures:Chronotype, measured via a continuous scale with higher scores indicating greater evening preferences, and social jet lag, measured as the continuous difference in actigraphy sleep midpoint in hours from midnight on weekends vs weekdays, with higher values representing more delayed sleep timing on weekends. Main Outcomes and Measures:Adiposity, measured via anthropometry and dual-energy x-ray absorptiometry. For a subset of 479 adolescents with blood samples, cardiometabolic risk scores were computed as the mean of 5 sex- and cohort-specific z scores for waist circumference, systolic blood pressure, inversely scaled high-density lipoprotein cholesterol, and log-transformed triglycerides and homeostatic model of insulin resistance. Results:Among the 804 adolescents in the study, 418 were girls and 386 were boys, with a mean (SD) age of 13.2 (0.9) years. In multivariable models adjusted for age, puberty, season, and sociodemographics, associations of chronotype and social jet lag with adiposity varied by sex. For girls, greater evening preference was associated with a 0.58-cm (95% CI, 0.12-1.03 cm; P?=?.04 for interaction) higher waist circumference and 0.16 kg/m2 (95% CI, 0.01-0.31 kg/m2; P?=?.03 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry; each hour of social jet lag was associated with a 1.19-cm (95% CI, 0.04-2.35 cm; P?=?.21 for interaction) higher waist circumference and 0.45 kg/m2 (95% CI, 0.09-0.82 kg/m2; P?=?.01 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry. Associations of social jet lag and evening chronotypes persisted for many measures of adiposity after adjustment for sleep duration and other lifestyle behaviors. By contrast, no associations were observed in boys. There were no associations with the cardiometabolic risk score for either sex, although statistical power was low for this outcome. Conclusions and Relevance:Evening chronotypes and social jet lag were associated with greater adiposity in adolescent girls but not adolescent boys. Interventions aimed at improving sleep schedules may be useful for obesity prevention, especially in girls.
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Project description:BackgroundChildhood cancer survivors experience significantly higher rates of hypertension which potentiates cardiovascular disease, but the contribution and relationship of genetic and treatment factors to hypertension risk are unknown.ObjectivesTo determine the contribution of a blood pressure polygenic risk score (PRS) from the general population and its interplay with cancer therapies to hypertension in childhood cancer survivors.MethodsUsing 895 established blood pressure loci from the general population, we calculated a PRS for 3572 childhood cancer survivors of European ancestry from Childhood Cancer Survivor Study (CCSS) original cohort, 1889 from CCSS expansion cohort, and 2534 from the St. Jude Lifetime Cohort (SJLIFE). Hypertension was assessed using National Cancer Institute criteria based on self-report of a physician diagnosis in CCSS and by blood pressure measurement in SJLIFE.ResultsIn the combined sample of 7995 survivors, those in the top decile of the PRS had an odds ratio (OR) of 2.66 (95% CI=2.03-3.48) for hypertension compared to survivors in the bottom decile. The PRS-hypertension association was modified by being overweight/obese (per SD interaction OR=1.13; 95% CI=1.01-1.27) and exposure to hypothalamic-pituitary axis radiation (per SD interaction OR=1.18; 95% CI=1.05-1.33). Attributable fractions for hypertension to the PRS and cancer therapies were 21.0% and 15.7%, respectively, they jointly accounted for 40.2% of hypertension among survivors.ConclusionsA blood pressure PRS from the general population is significantly associated with hypertension among childhood cancer survivors and contributes to approximately one quarter of hypertension risk among survivors. These findings highlight the importance of screening for hypertension in all childhood cancer survivors, and identify higher risk subgroups.
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