Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy

Highlights: Adults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood. Background: Individuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy. Methods: We compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline. Results: Individuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (p<0.001for interaction between time and MONW status). Physical activity decreased relatively more since youth in individuals with adult MONW (p<0.001). Conclusions: Relative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.publishedVersionPeer reviewe

Increase in adiposity from childhood to adulthood predicts a metabolically obese phenotype in normal-weight adults

Normal weight is associated with a favorable cardiometabolic risk profile and low risk of type 2 diabetes and cardiovascular disease. However, some normal-weight individuals—the “metabolically obese normal weight” (MONW)—show a cardiometabolic risk profile similar to the obese. Previous studies have shown that older age, central body fat distribution, and unfavorable lifestyle increase the risk of MONW. However, the role of early-life factors in MONW remains unknown. We examined the associations of early-life factors with adult MONW in 1178 individuals from the Cardiovascular Risk in Young Finns study who were followed up from childhood to adulthood. The strongest early predictor for adult MONW was an increase in BMI from childhood to adulthood (p = 3.1 × 10−11); each 1 SD increase in BMI z-score from childhood to adulthood led to a 2.56-fold increase in the risk of adult MONW (CI 95% = 1.94–3.38). Other significant predictors of adult MONW were male sex (OR = 2.38, 95% = 1.63–3.47, p = 7.0 × 10−6), higher childhood LDL cholesterol (OR = 1.41 per 1 SD increase in LDL cholesterol, CI 95% = 1.14–1.73, p = 0.001), and lower HDL cholesterol (OR = 1.51 per 1 SD decrease in HDL cholesterol, CI 95% = 1.23–1.85, p = 5.4 × 10−5). Our results suggest that an increase in adiposity from childhood to adulthood is detrimental to cardiometabolic health, even among individuals remaining normal weight.</p

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome : a systematic review and meta-analysis

Aims/hypothesis FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. Methods A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. Results A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10−11) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10−10). This translated into an approximately 3.3 kg/m2 increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. Conclusions/interpretation The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study

Funder: The NIHR Biomedical Research Centre in CambridgeFunder: Finnish Innovation Fund SitraFunder: Foundation for Paediatric ResearchFunder: Ministry of Social Affairs and Health of FinlandFunder: Yrjö Jahnsson FoundationFunder: Research Committee of the Kuopio University Hospital Catchment Area (State Research Funding)Funder: The city of KuopioFunder: The UK Medical Research CouncilFunder: Finnish Cultural FoundationFunder: Ministry of Education and Culture of FinlandFunder: Juho Vainio FoundationFunder: Paavo Nurmi FoundationFunder: Diabetes Research Foundation in FinlandFunder: Finnish Foundation for Cardiovascular ResearchFunder: Social Insurance Institution of FinlandAbstract: Aims/hypothesis: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. Methods: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6–9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. Results: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient β for intervention effect −0.33 [95% CI −0.62, −0.04], p = 0.026) and HOMA-IR (β for intervention effect −0.084 [95% CI −0.156, −0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. Conclusions/interpretation: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. Trial registration: ClinicalTrials.gov NCT01803776 Graphical abstrac

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study

Funder: Opetus- ja Kulttuuriministeriö; doi: http://dx.doi.org/10.13039/501100003126Funder: Sosiaali- ja Terveysministeriö; doi: http://dx.doi.org/10.13039/501100008487Abstract: Purpose: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. Methods: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6–9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. Results: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( − 0.05 vs. 0.00 mmol/L, regression coefficient (β) = − 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (β = − 0.0203, + 47% change in β) and butter-based spreads (β = − 0.0294, + 30% change in β), moderate-to-vigorous physical activity (β = − 0.0268, + 30% change in β), light physical activity (β = − 0.0274, + 29% change in β) and sedentary time (β = − 0.0270, + 30% change in β). The intervention had no effect on other plasma lipids. Conclusion: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. Clinical Trial Registry Number: NCT01803776, ClinicalTrials.go

Boreal forest soil carbon fluxes one year after a wildfire: Effects of burn severity and management

The extreme 2018 hot drought that affected central and northern Europe led to the worst wildfire season in Sweden in over a century. The Ljusdal fire complex, the largest area burnt that year (8995 ha), offered a rare opportunity to quantify the combined impacts of wildfire and post-fire management on Scandinavian boreal forests. We present chamber measurements of soil CO2 and CH4 fluxes, soil microclimate and nutrient content from five Pinus sylvestris sites for the first growing season after the fire. We analysed the effects of three factors on forest soils: burn severity, salvage-logging and stand age. None of these caused significant differences in soil CH4 uptake. Soil respiration, however, declined significantly after a high-severity fire (complete tree mortality) but not after a low-severity fire (no tree mortality), despite substantial losses of the organic layer. Tree root respiration is thus key in determining post-fire soil CO2 emissions and may benefit, along with heterotrophic respiration, from the nutrient pulse after a low-severity fire. Salvage-logging after a high-severity fire had no significant effects on soil carbon fluxes, microclimate or nutrient content compared with leaving the dead trees standing, although differences are expected to emerge in the long term. In contrast, the impact of stand age was substantial: a young burnt stand experienced more extreme microclimate, lower soil nutrient supply and significantly lower soil respiration than a mature burnt stand, due to a thinner organic layer and the decade-long effects of a previous clear-cut and soil scarification. Disturbance history and burn severity are, therefore, important factors for predicting changes in the boreal forest carbon sink after wildfires. The presented short-term effects and ongoing monitoring will provide essential information for sustainable management strategies in response to the increasing risk of wildfire