Search

BackgroundAntithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4).ObjectiveTo determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies.MethodsWe pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire.ResultsAmong 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment.ConclusionsAmong older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

BackgroundChildhood obesity is complex, and its aetiology is known to be multifaceted. The contribution of lifestyle behaviors, including poor diet and physical inactivity, to obesity remains unclear. Due to the current high prevalence, childhood obesity is an urgent public health priority requiring current and reliable data to further understand its aetiology. ObjectiveThe objective of this study is to explore the individual, family, and environmental factors associated with childhood overweight and obesity, with a specific focus on diet and physical activity. A secondary objective of the study is to determine the average salt intake and distribution of blood pressure in Irish children. MethodsA cross-sectional survey was conducted of children 8-11 years old in primary schools in Cork, Ireland. Urban schools were selected using a probability proportionate to size sampling strategy, and a complete sample of rural schools from one area in Cork County were invited to participate. Information collected included physical measurement data (anthropometric measurements, blood pressure), early morning spot and 24 hour urine samples, a 3 day estimated food diary, and 7 days of accelerometer data. Principal- (school head) reported, parent/guardian-reported, and child-reported questionnaires collected information on lifestyle behaviors and environmental attributes. The Cork Children’s Lifestyle Study (CCLaS) was designed by the Department of Epidemiology and Public Health in University College Cork, Ireland in 2011 and 2012. Piloting and modification of study methods was undertaken. Data collection took place between April 2012 and June 2013. ResultsOverall, 27/46 schools and 1075/1641 children, of which 623 were boys, participated. Preliminary data analysis is underway. It is anticipated that the results of the CCLaS study will be available in late 2014. ConclusionsThe CCLaS study has collected in-depth data on a wide range of individual, family, social, and environmental correlates which will allow us to access multilevel influences on childhood obesity. This study will contribute to the evidence base by highlighting current knowledge and gaps regarding the predominant drivers of childhood obesity.

BackgroundFatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue.MethodThis study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60-19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight

BackgroundChronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.MethodsIndividual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.ResultsA total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.ConclusionsLow thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

COVID-19 has challenged global health care systems and resulted in prehospital delays for time-sensitive emergencies, like stroke and transient ischemic attacks (TIA). However, there are conflicting international reports on the level of effect of the pandemic on ambulance response intervals and emergency call volumes for these conditions. The purpose of this study was to synthesize the international evidence on the effect of COVID-19 on ambulance response intervals and emergency call volume for suspected stroke and TIA. Following a published protocol, we conducted a systematic search of six databases through May 31, 2022. We re-ran this search on April 14, 2023, to check for any new papers. We considered for inclusion peer-reviewed quantitative studies comparing prehospital emergency care for adults with suspected stroke/TIA before and during the COVID-19 pandemic. Two authors screened title/abstract and full text articles. One author carried out data extraction, with a random selection of articles being checked by another author. We calculated overall pooled estimates of ambulance intervals (activation, response, patient care, and total prehospital intervals) and stroke/TIA emergency call volume. Subgroup and sensitivity analyses included location and stroke/TIA diagnosis. Two authors assessed study quality using the appropriate Joanna Briggs Institute tool. We worked with patient and public involvement contributors and clinical and policy stakeholders throughout the review. Of 4,083 studies identified, 52 unique articles met the inclusion criteria. Mean response interval (-1.29 min [-2.19 to -0.38]) and mean total prehospital interval (-6.42 min [-10.60 to -2.25]) were shorter in the pre-COVID-19 period, compared to the COVID-19 period. Furthermore, there was a higher incidence rate of emergency call volume for suspected stroke/TIA per day pre-COVID-19 compared with the COVID-19 period (log IRR = 0.17 [0.02 to 0.33]). Ambulance response interval definitions and terminology varied between regions and countries. Our review indicates that prehospital delays for suspected stroke/TIA increased during the COVID-19 pandemic. Furthermore, emergency call volume for suspected stroke/TIA decreased during this period. In order to minimize delays in future pandemics or other health care emergencies future research may involve understanding the potential reasons for these delays. [ABSTRACT FROM AUTHOR]

BackgroundSubclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH.MethodsParticipants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects

Aim: To explore factors affecting participation in the pilot of the synchronous online national diabetes prevention programme (NDPP) in Ireland from the perspectives of those who attended and the educators who recruited for and delivered the programme. Methods: A qualitative study involving semi‐structured interviews and focus groups with NDPP attenders (attended the assessment and at least one session) and educators (dietitians) on the programme. The Framework Method using the Theoretical Domains Framework (TDF) guided the analysis. Results: Thirteen attenders took part in two online focus groups and five online or phone interviews. Eight educators took part. Four themes which cut across the TDF domains were identified as factors influencing participation; (i) lack of awareness of prediabetes and fear of diabetes, relating to attenders' fear of diabetes and lack of knowledge of prediabetes and diabetes prevention; (ii) perceived need for programme support to change health behaviour, concerning attenders' and educators' recognition of the need for the NDPP; (iii) trust in healthcare professionals (HCPs), relating to trust in HCPs to convey the seriousness of prediabetes and the value of diabetes prevention programmes (DPPs) and (iv) practical and personal ease of joining online, relating to the flexibility and accessibility of the synchronous online group format, the IT skills of attenders and educators and apprehension about group education. Conclusions: Raising awareness of prediabetes and the need for prevention programmes should be a priority for health services and HCPs. The synchronous online group format was seen as less daunting to join than a face‐to‐face programme and may be a useful option to encourage participation. [ABSTRACT FROM AUTHOR]

There is a large body of literature demonstrating a social gradient in health and increasing evidence of an association between social deprivation and diabetes complications. Diabetic kidney disease (DKD) increases mortality in people with diabetes. Socioeconomic deprivation is increasingly recognized as a modifier of risk factors for kidney disease but also an independent risk factor itself for kidney disease. This may not be truly appreciated by clinicians and warrants further attention and exploration. In this review we explore the literature to date from Europe on the relationship between social deprivation and DKD. The majority of the studies showed at least an association with microalbuminuria, an early marker of DKD, while many showed an association with overt nephropathy. This was seen across many countries in Europe using a variety of different measures of deprivation. We reviewed and considered the mechanisms by which deprivation may lead to DKD. Health related behaviors such as smoking and suboptimal control of risk factors such as hypertension, hyperglycemia and elevated body mass index (BMI) accounts for some but not all of the association. Poorer access to healthcare, health literacy, and stress are also discussed as potential mediators of the association. Addressing deprivation is difficult but starting points include targeted interventions for people living in deprived circumstances, equitable roll out of diabetes technology, and flexible outpatient clinic arrangements including virtual and community‐based care. [ABSTRACT FROM AUTHOR]

Introduction Intervention fidelity refers to whether an intervention is delivered as intended and can enhance interpretation of trial outcomes. Fidelity of interventions to reduce or prevent stress and anxiety during pregnancy and postpartum has yet to be examined despite inconsistent findings for intervention effects. This study systematically reviews use and/or reporting of intervention fidelity strategies in trials of interventions, delivered to (expectant) parents during pregnancy and postpartum, to reduce or prevent stress and/or anxiety. Methods MEDLINE, Embase, CINAHL, PsychINFO, and Maternity and Infant Care were searched from inception to March 2019. Studies were included if they were randomised controlled trials including pregnant women, expectant fathers and/or partners during pregnancy, and/ or parents within the first two years postpartum. The National Institutes of Health Behavior Change Consortium checklist was used to assess fidelity across five domains (study design, provider training, delivery, receipt, enactment). Results Sixteen papers (14 interventions) were identified. Average reported use of fidelity strategies was 'low' (45%), ranging from 17.5 to 76%. Fidelity ratings ranged from 22% for provider training to 54% for study design. Conclusions Low levels of intervention fidelity may explain previous inconsistent effects of stress and anxiety reduction interventions. Important methodological areas for improvement include intervention provider training, fidelity of comparator conditions, and consideration of non-specific treatment effects. Increased methodological rigour in fidelity enhancement and assessment will improve intervention implementation and enhance examination of stress and anxiety reduction and prevention interventions delivered during pregnancy and the postpartum., Author(s): Gregory Gorman [sup.1] , Elaine Toomey [sup.2] , Caragh Flannery [sup.1] , Sarah Redsell [sup.3] , Catherine Hayes [sup.4] , Anja Huizink [sup.5] , Patricia M. Kearney [sup.1] , [...]

Objectives To examine the associations between preeclampsia and longitudinal child developmental and behavioural outcomes using data from a nationally representative study of children living in Ireland. Methods We used maternal-reported data from the Growing Up in Ireland longitudinal study of children. Data on preeclampsia and preeclampsia + small for gestational age (SGA) were collected when children were 9-months old. Data on child development and behavioural outcomes were collected at 9-months using the Ages and Stages Questionnaire (ASQ), and at 3 years, 5 years and 7-8 years using the Strengths and Difficulties Questionnaire (SDQ). Multivariate logistic regression analysis was used to examine the association between preeclampsia exposure and failure of ASQ domains, and abnormal SDQ domains. Linear spline multilevel models were used to examine the association between preeclampsia and preeclampsia + SGA and repeated measures of SDQ. All models controlled for several perinatal and sociodemographic factors. Results A total of 10,692 children were included in the study at baseline, representing a weighted total of 70,791. Multivariate logistic regression suggested that preeclampsia was not associated with failing any ASQ domain. Preeclampsia was associated with abnormal SDQ cut-off of emotional ([greater than or equal to] 5) and hyperactivity ([greater than or equal to] 7) domains at age 5 years only. In the linear spline model, mean SDQ score was higher at each time point in exposed groups. Conclusions for Practice While we did not find strong evidence of associations between preeclampsia and child developmental and behavioural outcomes overall, some associations between preeclampsia-exposure and subtle behavioural issues did persist. Further research is needed to replicate these findings, and determine the clinical significance of changes in SDQ scores., Author(s): Gillian M. Maher [sup.1] [sup.2] , Gerard W. O'Keeffe [sup.1] [sup.3] , Linda M. O'Keeffe [sup.2] , Karen Matvienko-Sikar [sup.2] , Christina Dalman [sup.4] [sup.5] , Patricia M. Kearney [...]

ImportanceSome experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).ObjectiveTo assess the association between differences in thyroid function within the reference range and CHD risk.Design, setting, and participantsIndividual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.ExposuresThyroid function as expressed by serum thyrotropin levels at baseline.Main outcomes and measuresHazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.ResultsAmong 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.Conclusions and relevanceThyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

ImportanceAssociations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.ObjectiveTo assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.Data sources and study selectionThe databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.Data extractionIndividual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of The Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value

ObjectiveThe associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.MethodsParticipants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).ResultsThere were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).ConclusionsThe associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

BackgroundSubclinical thyroid dysfunction is common among older people and has been associated with decreased functional capacity but with conflicting data. The aim of this study was to assess the association between subclinical thyroid dysfunction and functional capacity in an elderly population.MethodsWe included 5182 participants with a mean age of 75.2 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Self-reported functional capacity was assessed using the Barthel Index (BI) and the Instrumental Activities of Daily Living (IADL) scores at baseline and during follow-up. Participants with subclinical hyperthyroidism (n=65) and subclinical hypothyroidism (n=173) were compared to euthyroid participants (n=4944). The association between persistent subclinical thyroid dysfunction and functional capacity and decline was also investigated.ResultsAt baseline, compared to euthyroid participants (BI 19.73±SE 0.06; IADL 13.52±0.02), there was no difference in functional capacity for participants with subclinical hyperthyroidism (BI 19.60±0.09; IADL 13.51±0.12, p>0.05) or subclinical hypothyroidism (BI 19.82±0.06; IADL 13.55±0.08, p>0.05). Over a mean 3.2-year follow-up period, there was no association between thyroid function and annual decline of either BI or IADL (p>0.05). No association was found between persistent subclinical thyroid dysfunction and functional capacity at baseline or during follow-up (p>0.05). Results were similar after excluding participants with a maximum BI and/or IADL score at baseline.ConclusionAmong well-functioning community-dwelling elderly, we found no evidence that subclinical thyroid dysfunction contributes to decreased functional capacity.

Context: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. Objective: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. Design: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). Setting: Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. Participants: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the intrial placebo group (N = 361) was included. Main Outcome Measures: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. Results: In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. Conclusion: Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. [ABSTRACT FROM AUTHOR]

Background Sex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different associations of adiposity with cardiometabolic risk in females and males. We examined whether adiposity is differently associated with cardiometabolic trait levels in females and males at 3 different life stages. Methods and findings Data were from 2 generations (offspring, Generation 1 [G1] born in 1991/1992 and their parents, Generation 0 [G0]) of a United Kingdom population-based birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). Follow-up continues on the cohort; data up to 25 y after recruitment to the study are included in this analysis. Body mass index (BMI) and total fat mass from dual-energy X-ray absorptiometry (DXA) were measured at mean age 9 y, 15 y, and 18 y in G1. Waist circumference was measured at 9 y and 15 y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15 y, 18 y, and 25 y in G1. In G0, all 3 adiposity measures and the same 148 traits were available at 50 y. Using linear regression models, sex-specific associations of adiposity measures at each time point (9 y, 15 y, and 18 y) with cardiometabolic traits 3 to 6 y later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross-sectionally at 50 y. A total of 3,081 G1 and 4,887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males compared with females at younger ages (15 y to 25 y), and associations were more similar between the sexes or stronger in females at 50 y, particularly for apolipoprotein B-containing lipoprotein particles and lipid concentrations. For example, a 1 standard deviation (SD) (3.8 kg/m.sup.2) higher BMI at 18 y was associated with 0.36 SD (95% confidence interval [CI] = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25 y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females, P value for sex difference = 0.02. By contrast, at 50 y, a 1 SD (4.8 kg/m.sup.2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females, respectively, P value for sex difference = 0.42. Sex-specific associations of DXA-measured fat mass and waist circumference with cardiometabolic traits were similar to findings for BMI and cardiometabolic traits at each age. The main limitation of this work is its observational nature, and replication in independent cohorts using methods that can infer causality is required. Conclusions The results of this study suggest that associations of adiposity with adverse cardiometabolic risk begin earlier in the life course among males compared with females and are stronger until midlife, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts., Author(s): Linda M. O'Keeffe 1,2,3,*, Joshua A. Bell 2,3, Kate N. O'Neill 1, Matthew A. Lee 2,3, Mark Woodward 4,5, Sanne A. E. Peters 4,5,6, George Davey Smith 2,3, Patricia [...]