The association of adolescent fitness with cardiometabolic diseases in late adulthood: A 45-year longitudinal study

This work was supported by Emil Aaltonen Foundation under Grant 210097 O, Ellen ja Artturi Nyyssönen Foundation, and Juho Vainio Foundation under Grant 202300290.Objectives: The aim of this study was to examine the associations of adolescent cardiorespiratory fitness (CRF), muscular fitness (MF), and speed-agility fitness (SA) with middle-aged cardiometabolic disease risk and explore sex differences. Methods: This 45-year prospective cohort study examined the associations be- tween objectively measured fitness at adolescence (12–19 years) and physician- ascertained diabetes mellitus, elevated blood pressure (BP), and coronary heart disease reported either in early (37–44 years) or late (57–64 years) middle age, and self-measurement of waist circumference (WC) in late middle age. Fitness meas- urements for healthy adolescents in baseline included CRF (1.5 km [girls] and 2 km [boys] run), MF (standing broad jump, sit-ups, pull-ups [boys], and flexed- arm hang [girls]), and SA (50 m dash and 4 × 10 m shuttle run). Logistic regression and general linear models were adjusted for baseline age, sex, and body mass index (BMI), involving data from baseline and at least one follow-up measure- ment (N up to 1358, 47% males). Results: Adolescent CRF was inversely, and regardless of adiposity, associ- ated with middle age accumulated burden of cardiometabolic conditions in the whole sample (N = 562, ß = −0.10, 95% confidence intervals [CI] [−0.18, −0.03], p = 0.006), and elevated BP in females (N = 256, OR = 0.71, 95% CI [0.51, 0.91]). Overall, we observed stronger associations in females than in males. An inverse association of adolescent MF and SA with middle-aged WC was observed, but it did not show as consistent associations as with CRF. Conclusions: In this study, adolescent fitness, particularly CRF, was inversely as- sociated with the burden of cardiometabolic conditions up to 45 years. Promotion of fitness in youth may be beneficial in preventing adulthood cardiometabolic diseases.Emil Aaltonen Foundation 210097 OEllen ja Artturi Nyyssönen FoundationJuho Vainio Foundation 20230029

Association of Lipidome Remodeling in the Adipocyte Membrane with Acquired Obesity in Humans

The authors describe a new approach to studying cellular lipid profiles and propose a compensatory mechanism that may help maintain the normal membrane function of adipocytes in the context of obesity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3</jats:p

Leisure-time physical activity from adolescence to late middle age and its associations with the COVID-19 pandemic : A 45-year follow-up

We aimed to investigate the association of self-reported leisure-time physical activity (LTPA) over a 45-years from adolescence to late middle age mediated by LTPA in early middle age. We also explored whether LTPA in adolescence and early middle age was associated with change in LTPA during the COVID-19 pandemic. We constructed a path model employing questionnaire data from three LTPA measurements (1976, 2001, 2021) including duplicated assessment for pre- and during COVID-19 in 2021. The direct and indirect associations between LTPA in adolescence, early middle and late middle age were investigated, as well as the impact of previous LTPA on change in late middle age LTPA due to the pandemic. The number of participants per assessment was: n = 2083; n = 1468 (71% of the original); n = 878 (42%) and n = 867 (42%), respectively. However, the number varied depending on the path examined. LTPA in adolescence was associated with LTPA in late middle age, although the association was not strong. LTPA decreased significantly during the pandemic. Earlier LTPA was associated with change in LTPA between before and during COVID-19 among males. This study is the first to demonstrate an association between adolescent and late middle age LTPA. However, the association across the 45-years was low.peerReviewe

The association of adolescent fitness with cardiometabolic diseases in late adulthood : A 45‐year longitudinal study

Objectives The aim of this study was to examine the associations of adolescent cardiorespiratory fitness (CRF), muscular fitness (MF), and speed-agility fitness (SA) with middle-aged cardiometabolic disease risk and explore sex differences. Methods This 45-year prospective cohort study examined the associations between objectively measured fitness at adolescence (12–19 years) and physician-ascertained diabetes mellitus, elevated blood pressure (BP), and coronary heart disease reported either in early (37–44 years) or late (57–64 years) middle age, and self-measurement of waist circumference (WC) in late middle age. Fitness measurements for healthy adolescents in baseline included CRF (1.5 km [girls] and 2 km [boys] run), MF (standing broad jump, sit-ups, pull-ups [boys], and flexed-arm hang [girls]), and SA (50 m dash and 4 × 10 m shuttle run). Logistic regression and general linear models were adjusted for baseline age, sex, and body mass index (BMI), involving data from baseline and at least one follow-up measurement (N up to 1358, 47% males). Results Adolescent CRF was inversely, and regardless of adiposity, associated with middle age accumulated burden of cardiometabolic conditions in the whole sample (N = 562, ß = −0.10, 95% confidence intervals [CI] [−0.18, −0.03], p = 0.006), and elevated BP in females (N = 256, OR = 0.71, 95% CI [0.51, 0.91]). Overall, we observed stronger associations in females than in males. An inverse association of adolescent MF and SA with middle-aged WC was observed, but it did not show as consistent associations as with CRF. Conclusions In this study, adolescent fitness, particularly CRF, was inversely associated with the burden of cardiometabolic conditions up to 45 years. Promotion of fitness in youth may be beneficial in preventing adulthood cardiometabolic diseases.peerReviewe

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape

Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (Nature Communications, (2021), 12, 1, (24), 10.1038/s41467-020-19366-9)

The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped. This has now been corrected in the PDF and HTML versions of the Article

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q &#60; 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control