Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Transkriptionelles, proteomisches und metabolisches Netzwerk des Fur regulierten Eisenmetabolismus von Clostridium difficile

Clostridium difficile is known as a human pathogen causing diarrhea among patients in hospitals and health care units worldwide. C. difficile is a Gram-positive, strict anaerobic, spore-forming and toxin producing bacterium. In order to stop the growth of infectious microorganisms during infection the host restricts the excess to iron for the pathogens by producing iron- and siderophore-chelating proteins, by exporting iron from intracellular pathogen-containing compartments, and by limiting absorption of dietary iron. Consequently, infectious bacteria have to adjust their iron uptake and utilization strategies. Almost nothing was known about the regulation of iron uptake by C. difficile in the mammalian gut of the beginning of this thesis. Consequently, different possible iron sources were tested. A genomic knock out of the gene for the ferric uptake regulator Fur was generated using the ClosTron system. Fur displayed a clear growth deficiency compared to C. difficile wild type cells. Morphological experiments showed reduced flagella and pili formation in the fur mutant strain. Surprisingly, the toxin production was not affected by Fur. Subsequently, the wild type and fur mutant strain were subjected to a systems biology investigation using transcriptome, proteome and metabolome analyses to define the iron- and Fur regulon in C. difficile. Several iron-associated transporters as well as major energy metabolic pathways (e.g. L-leucine fermentation, proline metabolism, butyrate fermentation) are controlled in an iron dependent Fur regulated manner. Furthermore, flagella formation is positively regulated by iron and Fur. A consensus Fur-binding sequence was defined and potential Fur-boxes upstream of for example flagella associated genes and a ferrichrome transporter operon were found. Taken together, the regulator Fur is not only involved in the regulation of iron associated genes but also in processes of the central metabolism in C. difficile.Clostridium difficile ist ein humanpathogenes Bakterium, welches Durchfälle in Krankenhäusern weltweit verursacht. C. difficile ist ein Gram-positives, strikt anaerobes, sporenbildendes und Toxin bildendes Bakterium. Um das Wachstum von infektiösen Mikroorganismen während einer Infektion zu stoppen, bildet der Wirtsorganismus Eisen chelatierende Proteine. Folglich müssen Bakterien die Eisenaufnahme und Verwertung an die jeweiligen Bedingungen im Wirt anpassen und regulieren können. Zu Beginn dieser Arbeit war sehr wenig über das genregulatorische Netzwerk der Eisenaufnahme in C. difficile bekannt. Daher wurden verschiedene mögliche Eisenquellen getestet. Eine genomische Mutante des „ferric uptake regulators“ Fur wurde mittels des ClosTron Systems generiert. Die fur Mutante zeigte einen klaren Wachstumsdefizit gegenüber des Wildtyp Stammes. Morphologische Experimente zeigten, dass die fur Mutante im Vergleich zum Wildtyp weniger Flagellen und Pili produzierte. Interessanterweise konnte kein Zusammenhang zwischen der fur Mutation und der Toxinproduktion festgestellt werden. Im Anschluss wurde die fur Mutante in einem systembiologischen Versuch mittels Transkriptom, Proteom und Metabolom Analysen untersucht, um das Eisen- und Fur-Regulon in C. difficile zu definieren. Mehrere Eisenassozierte Transporter sowie Prozesse des zentralen Energiestoffwechsels (z.B. Leucin-Fermentation, Prolin-Fermentation und Butyrat/Butanol- Fermentation) werden in einer eisenabhängigen Fur-regulierten Weise gesteuert. Darüber hinaus wird die Flagellen Formation durch Eisen und die Fur Mutation positiv reguliert. Eine Konsensussequenz, die sogenannte Fur-Box, wurde definiert und potentielle Fur-Boxen konnten upstream von Flagellenassoziierten Genen sowie einem Ferrichrom-Operon gefunden werden. Zusammenfassend ist der Regulator Fur nicht nur an der Regulation von Eisentransportern, sondern auch an Prozessen des zentralen Stoffwechsels beteiligt

Iron Regulation in Clostridioides difficile.

The response to iron limitation of several bacteria is regulated by the ferric uptake regulator (Fur). The Fur-regulated transcriptional, translational and metabolic networks of the Gram-positive, pathogen Clostridioides difficile were investigated by a combined RNA sequencing, proteomic, metabolomic and electron microscopy approach. At high iron conditions (15 μM) the C. difficile fur mutant displayed a growth deficiency compared to wild type C. difficile cells. Several iron and siderophore transporter genes were induced by Fur during low iron (0.2 μM) conditions. The major adaptation to low iron conditions was observed for the central energy metabolism. Most ferredoxin-dependent amino acid fermentations were significantly down regulated (had, etf, acd, grd, trx, bdc, hbd). The substrates of these pathways phenylalanine, leucine, glycine and some intermediates (phenylpyruvate, 2-oxo-isocaproate, 3-hydroxy-butyryl-CoA, crotonyl-CoA) accumulated, while end products like isocaproate and butyrate were found reduced. Flavodoxin (fldX) formation and riboflavin biosynthesis (rib) were enhanced, most likely to replace the missing ferredoxins. Proline reductase (prd), the corresponding ion pumping RNF complex (rnf) and the reaction product 5-aminovalerate were significantly enhanced. An ATP forming ATPase (atpCDGAHFEB) of the F0F1-type was induced while the formation of a ATP-consuming, proton-pumping V-type ATPase (atpDBAFCEKI) was decreased. The [Fe-S] enzyme-dependent pyruvate formate lyase (pfl), formate dehydrogenase (fdh) and hydrogenase (hyd) branch of glucose utilization and glycogen biosynthesis (glg) were significantly reduced, leading to an accumulation of glucose and pyruvate. The formation of [Fe-S] enzyme carbon monoxide dehydrogenase (coo) was inhibited. The fur mutant showed an increased sensitivity to vancomycin and polymyxin B. An intensive remodeling of the cell wall was observed, Polyamine biosynthesis (spe) was induced leading to an accumulation of spermine, spermidine, and putrescine. The fur mutant lost most of its flagella and motility. Finally, the CRISPR/Cas and a prophage encoding operon were downregulated. Fur binding sites were found upstream of around 20 of the regulated genes. Overall, adaptation to low iron conditions in C. difficile focused on an increase of iron import, a significant replacement of iron requiring metabolic pathways and the restructuring of the cell surface for protection during the complex adaptation phase and was only partly directly regulated by Fur

Dietary patterns and their relationship with the perceptions of healthy eating in European adolescents : the HELENA study

Objective: The aim of this study was to identify dietary patterns (DPs) in European adolescents and to examine the association between perceptions of healthy eating and the obtained DPs. Method: A multinational cross-sectional study was carried out in adolescents aged 12.5 to 17.5?years and 2,027 (44.9% males) were considered for analysis. A self-reported questionnaire with information on food choices and preferences, including perceptions of healthy eating, and two 24-hour dietary recalls were used. Principal component analysis was used to obtain sex-specific DPs, and linear analyses of covariance were used to compare DPs according to perceptions of healthy eating. Results: Three and four DPs for boys and girls were obtained. In boys and girls, there were significant associations between some perceptions about healthy food and the Breakfast-DP (p?<?0.05). In boys, Breakfast-DP and Healthy Beverage-DP were associated with the perception of the own diet as healthy (p?<?0.05). Healthy Beverage-DP was associated with those disliking fruits and vegetables (p?<?0.05). Girls considering the own diet as healthy were associated with Mediterranean-DP, Breakfast-DP, and Unhealthy Beverage and Meat-DP (p?<?0.05). The perception of snacking as a necessary part of a healthy diet was associated with Breakfast-DP in both genders (p?<?0.05). Conclusions: In European adolescents, perceptions of healthy eating were mainly associated with a DP characterized by foods consumed at breakfast. Future studies should further explore these findings in order to implement health promotion programs to improve healthy eating habits in adolescents

Diet as a moderator in the association of sedentary behaviors with inflammatory biomarkers among adolescents in the HELENA study

AIM: To assess if a healthy diet might attenuate the positive sedentary-inflammation relation, whereas an unhealthy diet may increase the effect of sedentary behaviors on inflammatory biomarkers. METHODS: In 618 adolescents (13-17 years) of the European HELENA study, data were available on body composition, a set of inflammation markers, and food intake assessed by a self-administered computerized 24 h dietary recall for 2 days. A 9-point Mediterranean diet score and an antioxidant-rich diet z-score were used as dietary indices and tested as moderators. A set of low-grade inflammatory characteristics was used as outcome: several cytokines in an inflammatory ratio (IL-6, IL-10, TNF-α, TGFβ-1), C-reactive protein, three cell-adhesion molecules (sVCAM-1, sICAM-1, sE-selectin), three cardiovascular risk markers (GGT, ALT, homocysteine) and three immune cell types (white blood cells, lymphocytes, CD3). Sedentary behaviors were self-reported and analyzed as total screen time. Multiple linear regression analyses tested moderation by diet in the sedentary behaviors-inflammation association adjusted for age, sex, country, adiposity (sum of six skinfolds), parental education, and socio-economic status. RESULTS: Both diet scores, Mediterranean and antioxidant-rich diet, were significant protective moderators in the effect of sedentary behaviors on alanine-transaminase enzyme (P = 0.014; P = 0.027), and on the pro/anti-inflammatory cytokine ratio (P = 0.001; P = 0.004), but not on other inflammatory parameters. CONCLUSION: A higher adherence to the Mediterranean diet or an antioxidant-rich diet may attenuate the onset of oxidative stress signs associated by sedentary behaviors, whereas a poor diet seems to increase inflammation

Do dietary patterns determine levels of vitamin B6, folate, and vitamin B12 intake and corresponding biomarkers in European adolescents? The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

OBJECTIVES: To determine dietary patterns (DPs) and explain the highest variance of vitamin B6, folate, and B12 intake and related concentrations among European adolescents. METHODS: A total of 2173 adolescents who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence study met the eligibility criteria for the vitamin B intake analysis (46% boys) and 586 adolescents for the biomarkers analysis (47% boys). Two non-consecutive, 24-h, dietary recalls were used to assess the mean intakes. Concentrations were measured by chromatography and immunoassay testing. A reduced rank regression was applied to elucidate the combined effect of food intake of vitamin B and related concentrations. RESULTS: The identified DPs (one per vitamin B intake and biomarker and by sex) explained a variability between 34.2% and 23.7% of the vitamin B intake and between 17.2% and 7% of the biomarkers. In the reduced rank regression models, fish, eggs, cheese, whole milk and buttermilk intakes were loaded positively for vitamin B intake in both sexes; however, soft drinks and chocolate were loaded negatively. For the biomarkers, a higher variability was observed in the patterns in terms of food loads such as alcoholic drinks, sugars, and soft drinks. Some food items were loaded differently between intakes and biomarkers such as fish products, which was loaded positively for intakes but negatively for plasma folate in girls. CONCLUSIONS: The identified DPs explained up to 34.2% and 17.2% of the variability of the vitamin B intake and plasma concentrations, respectively, in European adolescents. Further studies are needed to elucidate the factors that determine such patterns

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure : A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20–29 years to 70–79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005–16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups