<jats:p>Young adults with a later chronotype are vulnerable for a discrepancy in sleep rhythm between work- and free days, called social jet lag (SJL). This study analysed (i) chronotype/SJL association with visceral fat/skeletal muscle mass, (ii) the attribution to physical activity behaviour, and (iii) chronotype-specific changes in physical activity behaviour in young adults during the Covid-19 pandemic lockdown. Chronotype and SJL were derived from the Munich-Chrono-Type-Questionnaire in 320 German students (age 18–25 years) from September 2019 to January 2020, 156 of these participated in an online follow-up survey in June 2020. Body composition was assessed by bioimpedance analysis at baseline. Multivariable linear regression analyses were used to relate chronotype/SJL to body composition; the contribution of self-reported physical activity was tested by mediation analysis. At baseline, a later chronotype and a larger SJL were associated with a higher visceral fat mass (P&lt;0.05), this relation was notably mediated by the attention to physical activity (P&lt;0.05). Chronotype (P = 0.02) but not SJL (P = 0.87) was inversely associated with skeletal muscle mass. During the pandemic lockdown, chronotype hardly changed, but SJL was reduced. Timing and physical activity behaviour remained in most participants and changes were unrelated to chronotype (all P&gt;0.07). A later chronotype/higher SJL may increase the risk of a higher visceral fat mass even in this relatively healthy sample, which may be partly due to their physical activity behaviour. Despite a reduction in SJL during the pandemic lockdown, later chronotypes did not change their physical activity behaviour more than earlier chronotypes.</jats:p>

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>The present work aimed to delineate (i) a revised protocol according to recent methodological developments in evidence generation, to (ii) describe its interpretation, the assessment of the overall certainty of evidence and to (iii) outline an Evidence to Decision framework for deriving an evidence-based guideline on quantitative and qualitative aspects of dietary protein intake.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A methodological protocol to systematically investigate the association between dietary protein intake and several health outcomes and for deriving dietary protein intake recommendations for the primary prevention of various non-communicable diseases in the general adult population was developed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The developed methodological protocol relies on umbrella reviews including systematic reviews with or without meta-analyses. Systematic literature searches in three databases will be performed for each health-related outcome. The methodological quality of all selected systematic reviews will be evaluated using a modified version of AMSTAR 2, and the outcome-specific certainty of evidence for systematic reviews with or without meta-analysis will be assessed with NutriGrade. The general outline of the Evidence to Decision framework foresees that recommendations in the derived guideline will be given based on the overall certainty of evidence as well as on additional criteria such as sustainability.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The methodological protocol permits a systematic evaluation of published systematic reviews on dietary protein intake and its association with selected health-related outcomes. An Evidence to Decision framework will be the basis for the overall conclusions and the resulting recommendations for dietary protein intake.</jats:p> </jats:sec>

<jats:sec><jats:title>Introduction</jats:title><jats:p>In 2012, the estimated global prevalence of pre-diabetes was 280 million, and the prevalence is expected to rise to 400 million by 2030. Oat-based foods are a good source of beta-glucans, which have been shown to lower postprandial blood glucose. Studies to evaluate the effectiveness of the long-term intake of beta-glucan-enriched bread as part of a habitual diet among individuals with pre-diabetes are needed. Therefore, we designed a multicentre intervention study in adults with pre-diabetes to investigate the effects of consumption of an oat-derived beta-glucan-enriched bread as part of a normal diet on glycated haemoglobin (HbA1c) in comparison to consumption of whole-grain wheat bread.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>The CarbHealth trial is a multicentre double-blind randomised controlled 16-week dietary intervention trial in participants 40–70 years of age with a body mass index of ≥27 kg/m<jats:sup>2</jats:sup> and HbA1c of 35–50 mmol/mol. The study is conducted at four universities located in Norway, Sweden and Germany and uses intervention breads specifically designed for the trial by Nofima AS. The aim is to recruit 250 participants. The primary outcome is the difference in HbA1c between the intervention and the control groups. The main analysis will include intervention group, study centre and baseline HbA1c as independent variables in an analysis of covariance model.</jats:p></jats:sec><jats:sec><jats:title>Ethics and dissemination</jats:title><jats:p>The study protocol was approved by respective ethical authorities in participating countries. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04994327">NCT04994327</jats:ext-link>.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>To examine the association between fructose intake in adolescence and fatty liver indices (hepatic steatosis index (HSI), fatty liver index (FLI)) in young adulthood.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Overall, 246 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had a fasting blood sample in adulthood (18–36 years), at least two 3-day weighed dietary records for calculating fructose intakes and other fructose-containing sugars (total (TS), free (FS), added sugar (AS)) as well as two complete 24-h urine samples for calculating sugar excretion (fructose excretion (FE), fructose + sucrose excretion (FE + SE)) in adolescence (males: 9.5–16.5 years; females: 8.5–15.5 years) were analysed using multivariable linear regression analyses.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>On the level of dietary intake, no prospective associations were observed between adolescent fructose intake and both adult fatty liver indices, whereas higher FS intakes were associated with lower levels of HSI (<jats:italic>P</jats:italic><jats:sub>trend</jats:sub> = 0.02) and FLI (<jats:italic>P</jats:italic><jats:sub>trend</jats:sub> = 0.03). On the urinary excretion level, however, a higher FE (P<jats:sub>trend</jats:sub> = 0.03) and FE + SE (<jats:italic>P</jats:italic><jats:sub>trend</jats:sub> = 0.01) in adolescence were prospectively related to higher adult FLI values. No associations were observed between adolescent sugar excretion and adult HSI.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The present study does not provide unambiguous support for a detrimental impact of adolescent fructose intake on adult liver health. Nonetheless, further examinations estimating exposure by means of urinary excretion as well as dietary intake levels appear warranted.</jats:p> </jats:sec>

<jats:p><jats:bold>Purpose:</jats:bold> To examine the prospective relevance of dietary sugar intake (based on dietary data as well as urinary excretion data) in adolescent years for insulin sensitivity and biomarkers of inflammation in young adulthood.</jats:p><jats:p><jats:bold>Methods:</jats:bold> Overall 254 participants of the DONALD study who had at least two 3-day weighed dietary records for calculating intakes of fructose, glucose, sucrose, total, free, added sugars, total sugars from sugar-sweetened beverages (SSB), juice, and sweets/sugar or at least two complete 24 h urine samples (<jats:italic>n</jats:italic> = 221) for calculating sugar excretion (urinary fructose and urinary fructose + sucrose) in adolescence (females: 9–15 years, males: 10–16 years) and a fasting blood sample in adulthood (18–36 years), were included in multivariable linear regression analyses assessing their prospective associations with adult homeostasis model assessment insulin sensitivity (HOMA2-%S) and a pro-inflammatory score (based on CRP, IL-6, IL-18, leptin, chemerin, adiponectin).</jats:p><jats:p><jats:bold>Results:</jats:bold> On the dietary intake level, no prospective associations were observed between adolescent fructose, sucrose, glucose, added, free, total sugar, or total sugar from SSB, juice or sweets/sugar intake and adult HOMA2-%S (<jats:italic>p</jats:italic> &amp;gt; 0.01). On the urinary level, however, higher excreted fructose levels were associated with improved adult HOMA2-%S (<jats:italic>p</jats:italic> = 0.008) among females only. No associations were observed between dietary or urinary sugars and the adult pro-inflammatory score (<jats:italic>p</jats:italic> &amp;gt; 0.01).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The present study did not provide support that dietary sugar consumed in adolescence is associated with adult insulin sensitivity. The one potential exception was the moderate dietary consumption of fructose, which showed a beneficial association with adult fasting insulin and insulin sensitivity.</jats:p>

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background/objectives</jats:title> <jats:p>Adolescence is a critical period for both the development of overweight and the transition toward a later chronotype, often accompanied by an increase in social jetlag. This study assessed whether changes in chronotype and social jetlag, are linked to changes in body composition during adolescence.</jats:p> </jats:sec><jats:sec> <jats:title>Subjects/methods</jats:title> <jats:p>We used data from the DONALD open cohort study, collected between 2014 and 2019, from 213 adolescents (9–17 years at baseline, 45% females) having at least two measures of chronotype and anthropometry (<jats:italic>N</jats:italic> = 572). Chronotype was assessed with the Munich Chronotype Questionnaire and defined as: midpoint of sleep corrected for sleep-debt (MSFsc) accumulated over the week (later MSFsc represents later chronotype). Social jetlag (SJL) defines the difference between midpoint of sleep during week and weekend. Calculations for Fat Free Mass Index (FFMI [kg/m<jats:sup>2</jats:sup>)]) and Fat Mass Index (FMI) [kg/m<jats:sup>2</jats:sup>)]) were based on body fat percentage, weight, and height. To analyze the associations, we used linear mixed-effect regression models. Finally, the total cohort was split into three biologically relevant age groups (cut-off set at &lt;12 years, ≥12 to ≤15 years and &gt;15 years).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Median follow-up was 2.1 years. Overall, change toward a later chronotype was significantly related with an increase in FMI (ß: 0.05, 95% CI: 0.01–0.08). A 1 h increase in social jetlag predicted an increase in BMI-SDS of 0.08 SDS units (95% CI: 0.01–0.14) and in FMI of 0.04 kg/m2 (95% CI: 0.003–0.08). Associations were stronger for the age group ≥12 to ≤15 years (<jats:italic>p</jats:italic> for interaction: &lt;0.001). No relationship was found with FFMI.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Changes in MSFsc and SJL during adolescence were associated with concurrent changes in BMI-SDS and FMI. The age ≥12 to ≤15 years appears to be a sensitive period in which chronobiological changes were clearly associated with increasing body fatness.</jats:p> </jats:sec>

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Reliable tables of glycemic indexes (GIs) and glycemic loads (GLs) are critical to research examining the relationship between glycemic qualities of carbohydrate in foods, diets, and health. In the 12 years since the last edition of the tables, a large amount of new data has become available.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>To systematically review and tabulate published and unpublished sources of reliable GI values, including an assessment of the reliability of the data.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This edition of the tables lists over 4000 items, a 61% increase in the number of entries compared to the 2008 edition. The data have been separated into 2 lists. The first represents more precise values derived using the methodology recommended by the International Standards Organization (∼2100 items). The second list contains values determined using less robust methods, including using limited numbers of healthy subjects or with a large SEM (∼1900 food items).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Dairy products, legumes, pasta, and fruits were usually low-GI foods (≤55 on the 100-point glucose scale) and had consistent values around the world. Cereals and cereal products, however, including whole-grain or whole-meal versions, showed wide variation in GI values, presumably arising from variations in manufacturing methods. Breads, breakfast cereals, rice, savory snack products, and regional foods were available in high-, medium-, and low-GI versions. Most varieties of potato were high-GI foods, but specific low-GI varieties have now been identified.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The availability of new data on the GIs of foods will facilitate wider research and application of the twin concepts of GI and GL. Although the 2021 edition of the tables improves the quality and quantity of GI data available for research and clinical practice, GI testing of regional foods remains a priority. This systematic review was registered in PROSPERO as #171204.</jats:p> </jats:sec>

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Studies about effects of lunch dietary Glycemic Index (GI) on cognition of schoolchildren are scarce. Our previous CogniDo GI study found no changes of cognition in the early postprandial phase after consumption of two rice types with medium vs. high dietary GI for lunch (i.e., 45 min after starting lunch). This study investigated whether the dietary GI of lunch has an impact on cognition of schoolchildren in the late postprandial phase, 90 min after lunch.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A randomized, 2 × 2 crossover intervention study was conducted at a comprehensive school with 5th and 6th grade students. Participants (<jats:italic>n</jats:italic> = 212) were randomly assigned to either sequence 1 or 2. In the first period, participants of sequence 1 received a dish with high GI rice (GI: 79), those of sequence 2 with medium GI rice (GI: 64)—in the second period, 1 week later, vice versa. Computer-based cognitive testing was performed 90 min after lunch examining tonic alertness, visual search and task switching, and working memory. Treatment effects and treatment effects adjusted for estimated lunch glycemic load (GL) were analyzed using a linear mixed model.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The selected cognitive parameters were not affected by the GI of lunch 90 min after lunch, neither after intention-to-treat nor in the per-protocol analysis. Adjustment for GL also did not change results.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The present study revealed no notable differences after the consumption of two rice types with medium vs. high dietary GI for lunch in children’s cognitive function in the late postprandial phase, 90 min after lunch.</jats:p> </jats:sec><jats:sec> <jats:title>Clinical trial registration</jats:title> <jats:p>German Clinical Trials Register (DRKS00013597); date of registration: 16/04/2018, retrospectively registered.</jats:p> </jats:sec>

<jats:title>Abstract</jats:title><jats:p>Flavonoids are suggested to reduce disease risk. Since dietary habits are acquired during early life, describing age and time trends of flavonoid intake and major food sources are important for monitoring and disease prevention in later life. We aimed to describe total flavonoid intake and food sources and to investigate age and time trends of flavonoid intake in 3–18-year-olds, from the Dortmund Nutritional and Anthropometric Longitudinally Designed study from 1985 to 2016. Intake was assessed annually using 3-d weighed food records (WFR). Flavonoid values were assigned using the United States Department of Agriculture database. Foods contributing to intake were determined. Age and time trends in total flavonoid and isoflavone density were analysed by sex with PROC MIXED. In total, 1312 children completed 10 758 WFR. Across all ages, daily mean total flavonoid density was lower in boys compared with girls (134 <jats:italic>v</jats:italic>. 146 mg/4184 kJ) and no difference in median isoflavone density (0·04 mg/4184 kJ per d) was found. The top five foods contributing to total flavonoid intake were apple with peel (15·0/17·1 %), strawberries (5·9/6·1 %), chocolate spread (3·9/3·5 %), orange juice (3·5/3·4 %) and pasta (3·5/3·4 %) for boys and girls, respectively. Overall, in boys, total flavonoid density decreased over the course of age and time. In girls, there was no association with age or time. In both sexes, isoflavone density followed a U-shaped age trend with no change over time. From a public health perspective, the overall observed downwards trend of flavonoid intake in boys deserves attention. Future initiatives should be tailored at maintaining a high flavonoid density as children age, specifically among boys.</jats:p>

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To provide a systematic overview of world dietary sugar and sugar-sweetened beverage (SSB) intake trends in children and adolescents.</jats:p> </jats:sec> <jats:sec> <jats:title>Data Sources</jats:title> <jats:p>Medline, Embase, and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched through January 2019 to identify longitudinal follow-up studies with time-trend data and repeated cross-sectional studies.</jats:p> </jats:sec> <jats:sec> <jats:title>Data Extraction</jats:title> <jats:p>Data from studies reporting ≥ 2 measurements (sugars, SSB, or sweets/candy) over ≥ 2 years and included ≥ 20 healthy, normal- or overweight children or adolescents aged 1–19 years.</jats:p> </jats:sec> <jats:sec> <jats:title>Data Analysis</jats:title> <jats:p>Data from 43 articles (n = 4 prospective cohort studies; n = 39 repeated cross-sectional studies) from 15 countries (n = 8 European countries plus Australia, Canada, China, South Korea, Mexico, Russia, and the United States) are presented narratively. According to the risk of bias in nonrandomized studies of interventions tool, 34 studies were judged to have a moderate risk of bias, and 5 to have a serious risk of bias.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Consumption among US children and adolescents increased substantially in the decades preceding 2000, followed by a faster and continued decline. As a whole, other international intake trends did not reveal drastic increases and decreases in SSB and dietary sugars; they tended to change only slightly across 3 decades.</jats:p> </jats:sec>

<jats:p>Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.</jats:p>

<jats:p> A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney’s capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18–25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny’s (B&amp;K’s) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&amp;K’s mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the “natural indirect effects” of WC on 24-h pH via leptin ( P = 0.01) and adiponectin ( P = 0.03) to be significant, with a trend for sICAM-1 ( P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity. </jats:p>

<jats:title>Abstract</jats:title><jats:p>Trend analyses based on dietary records suggest decreases in the intakes of total sugar (TS), added and free sugar since 2005 among children and adolescents in Germany. In terms of age trends, TS intake decreased with increasing age. However, self-reported sugar intake in epidemiological studies is criticised, as it may be prone to bias due to selective underreporting. Furthermore, adolescents are more susceptible to underreporting than children. We thus analysed time and age trends in urinary fructose excretion (FE), sucrose excretion (SE) and the sum of both (FE + SE) as biomarkers for sugar intake among 8·5–16·5-year-old adolescents. Urinary sugar excretion was measured by UPLC-MS/MS in 997 24-h urine samples collected from 239 boys and 253 girls participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study cohort between 1990 and 2016. Time and age trends of log-transformed FE, SE and FE + SE were analysed using polynomial mixed-effects regression models. Between 1990 and 2016, FE as well as FE + SE decreased (linear time trend: <jats:italic>P</jats:italic> = 0·0272 and <jats:italic>P</jats:italic> &lt; 0·0001, respectively). A minor increase in excretion during adolescence was confined to FE (linear age trend: <jats:italic>P</jats:italic> = 0·0017). The present 24-h excretion measurements support a previously reported dietary record-based decline in sugar intake since 2005. However, the previously seen dietary record-based decrease in TS from childhood to late adolescence was not confirmed by our biomarker analysis, suggesting a constant sugar intake for the period of adolescence.</jats:p>

<jats:p>There is no question that elevated postprandial glycemia is a significant driver of common chronic diseases globally [...]</jats:p>

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>There is controversy on the relevance of dietary sugar intake for cardiometabolic health.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>The aim of this network meta-analysis (NMA) was to assess how isocaloric substitutions of dietary sugar with other carbohydrates affect cardiometabolic risk factors, comparing different intervention studies.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We included randomized controlled trials (RCTs) investigating the isocaloric effect of substituting dietary sugars (fructose, glucose, sucrose) with other sugars or starch on cardiometabolic risk markers, including LDL cholesterol, triacylglycerol (TG), fasting glucose (FG), glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), uric acid, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), and liver fat content. To identify the most beneficial intervention for each outcome, random-effects NMA was conducted by calculating pooled mean differences (MDs) with 95% CIs, and by ranking the surface under the cumulative ranking curves (SUCRAs). The certainty of evidence was evaluated using the Confidence In Network Meta-Analysis tool.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Thirty-eight RCTs, including 1383 participants, were identified. A reduction in LDL-cholesterol concentrations was shown for the exchange of sucrose with starch (MD: −0.23 mmol/L; 95% CI: −0.38, −0.07 mmol/L) or fructose with starch (MD: −0.22 mmol/L; 95% CI: −0.39, −0.05 mmol/L; SUCRAstarch: 98%). FG concentrations were also lower for the exchange of sucrose with starch (MD: −0.14 mmol/L; 95% CI: −0.29, 0.01 mmol/L; SUCRAstarch: 91%). Replacing fructose with an equivalent energy amount of glucose reduced HOMA-IR (MD: −0.36; 95% CI: −0.71, −0.02; SUCRAglucose: 74%) and uric acid (MD: −23.77 µmol/L; 95% CI: −44.21, −3.32 µmol/L; SUCRAglucose: 93%). The certainty of evidence was rated very low to moderate. No significant effects were observed for TG, HbA1c, CRP, ALT, and AST.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our findings indicate that substitution of sucrose and fructose with starch yielded lower LDL cholesterol. Insulin resistance and uric acid concentrations were beneficially affected by replacement of fructose with glucose. Our findings are limited by the very low to moderate certainty of evidence. This review was registered at www.crd.york.ac.uk/prospero as CRD42018080297.</jats:p> </jats:sec>

<jats:p>Trend analyses suggest that free sugar (FS) intake—while still exceeding 10%E—has decreased among German children and adolescents since 2005, yet that intakes may shift from sugars naturally occurring in foods to added sugars as children age. Thus, we analysed time and age trends in FS intake (%E) from food groups among 3–18 year-olds (1985–2016) using 10,761 3-day dietary records from 1312 DONALD participants (660 boys, 652 girls) by use of polynomial mixed-effects regression models. Among girls, FS from sugar &amp; sweets decreased from 1985 to 2016 (linear trend p &lt; 0.0001), but not among boys (p &gt; 0.05). In the total sample, FS intake from juices increased until 2000 and decreased since 2005 (linear, quadratic trend p &lt; 0.0001). FS from sugar sweetened beverages (SSB) decreased non-linearly from 1985 to 2016 (girls: linear, quadratic, cubic trend p &lt; 0.0001; boys: linear, quadratic, cubic trend p &lt; 0.02). Younger children consumed more FS from juices than older ones, who had a higher FS intake from SSB. FS intake from sugar &amp; sweets increased until early adolescence and decreased afterwards. Since sugar &amp; sweets represent the main source of FS intake and the source with the least pronounced decline in intake, public health measures should focus on these products.</jats:p>

<jats:p>Published meta-analyses indicate significant but inconsistent incident type-2 diabetes (T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is now over a decade ago that a published meta-analysis used a predefined standard to identify valid studies. Considering valid studies only, and using random effects dose–response meta-analysis (DRM) while withdrawing spurious results (p &lt; 0.05), we ascertained whether these relations would support nutrition guidance, specifically for an RR &gt; 1.20 with a lower 95% confidence limit &gt;1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). The combined T2D–GI RR was 1.27 (1.15–1.40) (p &lt; 0.001, n = 10 studies) per 10 units GI, while that for the T2D–GL RR was 1.26 (1.15–1.37) (p &lt; 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet. The corresponding global DRM using restricted cubic splines were 1.87 (1.56–2.25) (p &lt; 0.001, n = 10) and 1.89 (1.66–2.16) (p &lt; 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000 kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GL were robustly associated with incident T2D. Together with mechanistic and other data, this supports that consideration should be given to these dietary risk factors in nutrition advice. Concerning the public health relevance at the global level, our evidence indicates that GI and GL are substantial food markers predicting the development of T2D worldwide, for persons of European ancestry and of East Asian ancestry.</jats:p>

<jats:p>While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill’s criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost–benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.</jats:p>

<jats:p>This study performed comparative analyses in two pediatric cohorts to identify dietary patterns during primary school years and examined their relevance to body composition development. Nutritional and anthropometric data at the beginning of primary school and two or four years later were available from 298 and 372 participants of IDEFICS-Germany (Identification and prevention of Dietary-induced and lifestyle-induced health Effects In Children and infants Study) and the KOPS (Kiel Obesity Prevention Study) cohort, respectively. Principal component analyses (PCA) and reduced rank regression (RRR) were used to identify dietary patterns at baseline and patterns of change in food group intake during primary school years. RRR extracted patterns explaining variations in changes in body mass index (BMI), fat mass index (FMI), and waist-to-height-ratio (WtHR). Associations between pattern adherence and excess gain in BMI, FMI, or WtHR (&gt;75th percentile) during primary school years were examined using logistic regression. Among PCA patterns, only a change towards a more Mediterranean food choice during primary school years were associated with a favorable body composition development in IDEFICS-Germany (p &lt; 0.05). In KOPS, RRR patterns characterized by a frequent consumption of fast foods or starchy carbohydrate foods were consistently associated with an excess gain in BMI and WtHR (all p &lt; 0.005). In IDEFICS-Germany, excess gain in BMI, FMI, and WtHR were predicted by a frequent consumption of nuts, meat, and pizza at baseline and a decrease in the consumption frequency of protein sources and snack carbohydrates during primary school years (all p &lt; 0.01). The study confirms an adverse impact of fast food consumption on body composition during primary school years. Combinations of protein and carbohydrate sources deserve further investigation.</jats:p>

<jats:title>Abstract</jats:title><jats:p> Background Children with migration background are at increased risk for overweight, partly due to less favorable dietary habits compared to their German counterparts. We examined the effects of practical nutrition lessons among children with a high proportion of migration background in a primary school setting.</jats:p><jats:p> Methods Ten 3rd and 4th grade classes (n=166 children, 73% with migration background) received the intervention and nine school classes (n=139 children, 76% with migration background) served as control. Before, shortly after (only among the intervention group) and three months after the three-day practical nutrition lessons, the nutrition-related skills, behavior, attitudes, and knowledge of the children were assessed using a questionnaire. Changes between baseline and 1st follow-up among children of the intervention group were calculated using linear mixed models. Differences between the two groups for changes between baseline and 2nd follow-up were tested using linear regression analyses. Models were adjusted for potential confounders.</jats:p><jats:p> Results Shortly after the practical nutrition lessons, the children of the intervention group had improved their knowledge (β=1.7; 95% CI: 1.0; 2.4, P&lt;0.001) and skills (β=1.8; 95% CI: 1.4; 2.2, P&lt;0.001). These changes were sustainable and larger in the intervention compared to the control group (knowledge: β=1.6; 95% CI: 0.7; 2.5, P&lt;0.001; skills: β=1.3; 95% CI: 0.7; 1.9, P&lt;0.001). Changes in nutrition-related behavior and attitudes did not differ between the groups.</jats:p><jats:p> Conclusions Providing practical nutrition lessons in a primary school setting with a high proportion of children with immigrational background improved the children’s nutrition-related knowledge and skills.</jats:p>

<jats:title>Abstract</jats:title><jats:p>The present study describes time and age trends in morning and evening protein intakes and sources among German children and adolescents from 1985 to 2014. A total of 9757 three-day weighed dietary records of 1246 3- to 18-year-old participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were analysed using polynomial mixed-effects regression models. Morning protein intake increased over the study period by approximately 1 % of morning energy intake (linear trend <jats:italic>P</jats:italic> &lt; 0·0001), with the youngest and the oldest children having the highest protein intake (linear, quadratic trend <jats:italic>P</jats:italic> &lt; 0·0001). Evening protein intake increased over time by approximately 2 % of evening energy intake in girls (linear trend <jats:italic>P</jats:italic> &lt; 0·0001) and 1 % of evening energy intake in boys (quadratic trend <jats:italic>P</jats:italic> = 0·0313), with decreasing intake with age (girls: linear trend <jats:italic>P</jats:italic> &lt; 0·0001; boys: linear trend <jats:italic>P</jats:italic> = 0·0963). Time trends were largely due to increases in protein from ‘starchy foods’. In conclusion, morning and evening protein intakes increased modestly between 1985 and 2014; these increases were, however, not accompanied by increases in traditional protein sources (i.e. meat or dairy products).</jats:p>

<jats:title>Abstract</jats:title><jats:p> Background Children with migration background are at particular risk for overweight. We assessed the effects of a primary school-based initiative targeted at enhancing physical activity and dietary education among children with a high proportion of migration background.</jats:p><jats:p> Methods Four 3rd and 4th grade classes (n=70 children, 77% with migration background) participated in a 10-months intervention comprising 2 additional exercise lessons weekly and 10 nutrition lessons per school year. 6 school classes (n=125 children, 65% with migration background) served as control. Before and after the intervention, an assessment of physical fitness and motor skills and questionnaires on dietary behavior and knowledge were conducted. In a subgroup (n=37), after 6 months of the intervention, daily physical activity was assessed by accelerometer-based monitoring. Differences in changes between the groups were assessed using linear regression analyses.</jats:p><jats:p> Results Changes between the 2 time points for fitness and motor skill tests (differences in standard deviation scores) were larger in the intervention than in the control group for the total mean test value (β=0.38, p&lt;0.001), driven by higher improvements in 5 of the 8 test items, i.e., obstacle race (speed) (β=0.22, p=0.049), standing long jump (strength) (β=0.35, p&lt;0.001), sit-ups (strength) (β=0.33, p=0.002), stand and reach (mobility) (β=0.22, p=0.042), and 6 min run (endurance) (β=0.40, p&lt;0.001), independently of confounders. Changes in dietary knowledge and consumption frequencies did not differ between groups.</jats:p><jats:p> Conclusions Promoting guided physical activity in a primary school setting with a high proportion of children with migration background positively affected parameters of fitness and motor skills.</jats:p>

<jats:title>Abstract</jats:title><jats:p>Given that commercial complementary food (CF) can contain high levels of added sugar, a high consumption may predispose to a preference for sweet taste later in life. This study examined cross-sectional associations between commercial CF consumption and added sugar intake in infancy as well as its prospective relation to added sugar intake in pre-school and primary-school age children. In all, 288 children of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with 3-d weighed dietary records at 0·5 and 0·75 (infancy), 3 and 4 (pre-school age) and 6 and 7 years of age (primary-school age) were included in this analysis. Individual commercial CF consumption as percentage of total commercial CF (%cCF) was averaged at 0·5 and 0·75 years. Individual total added sugar intake (g/d, energy percentage/d) was averaged for all three age groups. Multivariable logistic and linear regression models were used to analyse associations between %cCF and added sugar intake. In infancy, a higher %cCF was associated with odds for high added sugar intake from CF and for high total added sugar intake (&gt;75th percentile, <jats:italic>P</jats:italic>&lt;0·033). Prospectively, a higher %cCF was related to higher added sugar intake in both pre-school (<jats:italic>P</jats:italic>&lt;0·041) and primary-school age children (<jats:italic>P</jats:italic>&lt;0·039), although these associations were attenuated in models adjusting for added sugar intake in infancy. A higher %cCF in infancy may predispose to higher added sugar intake in later childhood by virtue of its added sugar content. Therefore, offering home-made CF or carefully chosen commercial CF without added sugar might be one strategy to reduce sugar intake in infancy and later on.</jats:p>

Background Understanding changes in dietary intake during puberty could aid the mapping of dietary interventions for primary prevention. The present study describes dietary changes from childhood to adolescence, and their associations with parental education, family income, child education, body mass index (BMI), pubertal onset and screen-time sedentary behaviour. Methods Dietary data (n = 1232) were obtained from food frequency questionnaires at the 10- and 15-year follow-ups of the GINIplus birth cohort study. Intakes of 17 food groups, macronutrients and antioxidant vitamins, were described by a) paired Wilcoxon rank sum tests, comparing average intakes at each time-point, and b) Cohen’s kappa “tracking” coefficients, measuring stability of intakes (maintenance of relative tertile positions across time). Further, associations of changes (tertile position increase or decrease vs. tracking) with parental education, family income, child education, pubertal onset, BMI, and screen-time, were assessed by logistic regression and multinomial logistic regression models stratified by baseline intake tertile. Results Both sexes increased average intakes of water and decreased starchy vegetables, margarine and dairy. Females decreased meat and retinol intakes and increased vegetables, grains, oils and tea. Males decreased fruit and carbohydrates and increased average intakes of meat, caloric drinks, water, protein, fat, polyunsaturated fatty acids (PUFAs), vitamin C and alpha-tocopherol. Both sexes presented mainly “fair” tracking levels [κw = 0.21–0.40]. Females with high (vs. low) parental education were more likely to increase their nut intake [OR = 3.8; 95 % CI = (1.7;8.8)], and less likely to decrease vitamin C intakes [0.2 (0.1;0.5)], while males were less likely to increase egg consumption [0.2 (0.1;0.5)] and n3 PUFAs [0.2 (0.1;0.5)]. Females with a higher (vs. low) family income were more likely to maintain medium wholegrain intakes [0.2 (0.1;0.7) for decrease vs. tracking, and 0.1 (0.0;0.5) for increase vs. tracking], and were less likely to decrease vitamin C intakes [0.2 (0.1;0.6)]. Males with high education were less likely to increase sugar-sweetened foods [0.1 (0.1;0.4)]. Finally, BMI in females was negatively associated with decreasing protein intakes [0.7 (0.6;0.9)]. In males BMI was positively associated with increasing margarine [1.4 (1.1;1.6)] and vitamin C intakes [1.4 (1.1;1.6)], and negatively associated with increasing n3 PUFA. Conclusions Average dietary intakes changed significantly, despite fair tracking levels, suggesting the presence of trends in dietary behaviour during puberty. Family income and parental education predominantly influenced intake changes. Our results support the rationale for dietary interventions targeting children, and suggest that sex-specific subpopulations, e.g. low socio-economic status, should be considered for added impact.

<jats:title>Abstract</jats:title><jats:p>The growth hormone (GH) insulin-like growth factor (IGF) axis has been linked to insulin metabolism and cancer risk. Experimental evidence indicates that the GH–IGF axis itself can be influenced by dietary flavonoids. As fruit and vegetable (FV) intake is a major source of flavonoid consumption, FV’s beneficial health effects may be explained via flavonoids’ influence on the GH–IGF axis, but observational evidence is currently rare. We used data from Dortmund Nutritional and Anthropometric Longitudinally Designed Study participants to analyse prospective associations between FV, fruit intake and flavonoid intake from FV (FlavFV) with IGF-1 and its binding proteins IGFBP-2 and IGFBP-3. Subjects needed to provide a fasting blood sample in adulthood (18–39 years) and at least two 3-d weighed dietary records in early life (0·5−2 years,<jats:italic>n</jats:italic>191), mid-childhood (3−7 years,<jats:italic>n</jats:italic>265) or adolescence (girls: 9−15 years, boys: 10−16 years,<jats:italic>n</jats:italic>261). Additional analyses were conducted among those providing at least three 24-h urine samples in adolescence (<jats:italic>n</jats:italic>236) to address the predictor urinary hippuric acid (HA), a biomarker of polyphenol intake. Higher fruit intake in mid-childhood and adolescence was related to higher IGFBP-2 in adulthood (<jats:italic>P</jats:italic>=0·03 and<jats:italic>P</jats:italic>=0·045). Comparable trends (<jats:italic>P</jats:italic>=0·045−0·09) were discernable for FV intake (but not FlavFV) in all three time windows. Similarly, higher adolescent HA excretion tended to be related (<jats:italic>P</jats:italic>=0·06) to higher adult IGFBP-2 levels. Regarding IGFBP-3, a marginal (<jats:italic>P</jats:italic>=0·08) positive association was observed with FlavFV in mid-childhood only. None of the investigated dietary factors was related to IGF-1. In conclusion, higher fruit and FV intakes during growth may be relevant for adult IGFBP-2, but probably not for IGFBP-3 or IGF-1.</jats:p>

<jats:p>Primary school years seem to represent a critical period for the development of overweight and obesity. However, only a few studies have analysed the prospective relationship between dietary patterns and weight status in children. The aims of the present study were to identify dietary patterns at the beginning of and during the primary school period and to examine their relevance to the development of body composition. Nutritional and anthropometric data from 371 participants of the Dortmund Nutritional and Longitudinally Designed (DONALD) Study at the beginning (ages 6 and 7 years) and end (ages 10 and 11 years) of the primary school period were used. Principal component analyses (PCA) were conducted to identify dietary patterns, which were regressed on changes in BMI and fat mass index (FMI) between ages 6 and 7 years and ages 10 and 11 years. Reduced rank regression (RRR) was used to directly extract patterns explaining variation in changes in BMI and FMI between ages 6 and 7 years and ages 10 and 11 years. PCA yielded interpretable patterns of dietary changes at the beginning of and during the primary school period, which were not related to changes in body composition. Conversely, RRR allowed identifying predictive patterns: higher baseline intakes of white bread and lower baseline intakes of whole-grain products as well as increases in the consumption of savoury snacks, sausages and cheese during primary school years independently predicted increases in BMI and FMI during the primary school period. In conclusion, selection of unfavourable carbohydrate sources at the beginning of the primary school period and increases in the consumption of processed savoury foods during primary school years may adversely affect the development of body composition during the course of primary school.</jats:p>

<jats:p>Non-alcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and obesity. Hence, carbohydrate quality could be of relevance to the risk of NAFLD, but prospective data are lacking. The aim of the present study was to investigate longitudinal associations between carbohydrate quality (including dietary glycaemic index (GI) and intakes of sugar, starch and fibre) and markers of liver function in an older Australian population. The analysis was based on 866 participants ( ≥ 49 years) of the Blue Mountains Eye Study with fasting blood specimens and dietary intake data at baseline and 5-year follow-up. Multi-level mixed regression analysis was used to relate dietary GI and sugar, starch and fibre intake to the liver enzymes alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT), as well as fasting TAG and HDL-cholesterol (HDL-C). After adjustment for potential confounding factors, a lower fibre intake was cross-sectionally related to higher GGT (<jats:italic>P</jats:italic>= 0·02) and fasting TAG (<jats:italic>P</jats:italic>= 0·002) levels, with fruit fibre being the most relevant fibre source (<jats:italic>P</jats:italic>= 0·095 for GGT; <jats:italic>P</jats:italic>= 0·003 for TAG). A higher dietary GI was associated with lower HDL-C (<jats:italic>P</jats:italic>= 0·046). Changes in carbohydrate quality during 5 years were not related to changes in ALT, GGT, TAG or HDL-C (<jats:italic>P</jats:italic>≥ 0·08). In conclusion, the absence of longitudinal associations between carbohydrate quality and liver enzymes and serum lipids in this older population does not support a major role of carbohydrate nutrition in liver function among the elderly.</jats:p>

<jats:title>Abstract</jats:title><jats:sec id="S1368980011002734_abs1" sec-type="general"><jats:title>Objective</jats:title><jats:p>Nutrition-related health problems such as obesity are frequent among children and adolescents of Turkish descent living in Germany, yet data on their dietary habits are scarce. One reason might be the lack of validated assessment tools for this target group. We therefore aimed to validate protein and K intakes from one 24 h recall against levels estimated from one 24 h urine sample in children and adolescents of Turkish descent living in Germany.</jats:p></jats:sec><jats:sec id="S1368980011002734_abs2" sec-type="general"><jats:title>Design</jats:title><jats:p>Cross-sectional analyses comprised estimation of mean differences, Pearson correlation coefficients, cross-classifications and Bland–Altman plots to assess the agreement between the nutritional intake estimated from a single 24 h recall and a single 24 h urine sample collected on the previous day.</jats:p></jats:sec><jats:sec id="S1368980011002734_abs3" sec-type="general"><jats:title>Setting</jats:title><jats:p>Dortmund, Germany.</jats:p></jats:sec><jats:sec id="S1368980011002734_abs4" sec-type="subjects"><jats:title>Subjects</jats:title><jats:p>Data from forty-three study participants (aged 5–18 years; 26 % overweight) with a traditional Turkish background were included.</jats:p></jats:sec><jats:sec id="S1368980011002734_abs5" sec-type="results"><jats:title>Results</jats:title><jats:p>The 24 h recall significantly overestimated mean protein and K intake by 10·7 g/d (95 % CI of mean difference: 0·6, 20·7 g/d) and 344 mg/d (95 % CI 8, 680 mg/d), respectively. Correlations between intake estimates were <jats:italic>r</jats:italic> = 0·25 (<jats:italic>P</jats:italic> = 0·1) and 0·31 (<jats:italic>P</jats:italic> = 0·05). Both methods classified 70 % and 69 % of the participants into the same/adjacent quartile of protein and K intake and misclassified 7 % and 7 %, respectively, into the opposite quartile. Bland–Altman plots indicated a wide scattering of differences in both protein and K intake.</jats:p></jats:sec><jats:sec id="S1368980011002734_abs6" sec-type="conclusion"><jats:title>Conclusions</jats:title><jats:p>Among children and adolescents of traditional Turkish descent living in Germany, one 24 h recall may only be valid for categorizing subjects into high, medium or low consumers.</jats:p></jats:sec>

<jats:p>There are no published data regarding the overall dietary glycaemic index (GI) and glycaemic load (GL) of Australian children and adolescents. We therefore aim to describe the dietary GI and GL of participants of the 2007 Australian National Children's Nutrition and Physical Activity Survey (2007ANCNPAS), and to identify the main foods contributing to their GL. Children, aged 2–16 years, who provided two 24 h recalls in the 2007ANCNPAS were included. A final dataset of 4184 participants was analysed. GI of each food item was assigned using a previously published method. GL was calculated, and food groups contributing to the GL were described by age group and sex. The weighted mean dietary GI and GL of the participants were 54 (<jats:sc>sd</jats:sc> 5) and 136 (<jats:sc>sd</jats:sc> 44), respectively. Among the nutrients examined, Ca had the highest inverse relationship with GI (<jats:italic>P</jats:italic> &lt; 0·001), while percentage energy from starch was most positively associated with GI. The association between fibre density and GI was modest, and percentage energy from sugar had an inverse relationship with GI. Daily dietary GL contributed by energy-dense and/or nutrient-poor (EDNP) items in subjects aged 14–16 years was more than doubled that of subjects aged 2–3 years. To conclude, Australian children and adolescents were having a high-GI dietary pattern characterised by high-starchy food intake and low Ca intake. A significant proportion of their dietary GL was from EDNP foods. Efforts to reduce dietary GI and GL in children and adolescents should focus on energy-dense starchy foods.</jats:p>

<jats:sec> <jats:title>Context:</jats:title> <jats:p>Whether prepubertal glucocorticoid status impacts on the timing of puberty is not clear.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>The objective of the study was to examine the relationship between prepubertal glucocorticoid status and early or late pubertal markers, independent of adrenarchal and nutritional status.</jats:p> </jats:sec> <jats:sec> <jats:title>Design and Participants:</jats:title> <jats:p>Prospective cohort study of healthy Caucasian children (n = 111, 56 boys) who provided both 24-h urine samples and weighed dietary records 1 and 2 yr before the start of pubertal growth spurt [age at take-off (ATO)].</jats:p> </jats:sec> <jats:sec> <jats:title>Measurements:</jats:title> <jats:p>Major urinary glucocorticoid and androgen metabolites determined by gas chromatography-mass spectrometry analysis were summed to assess daily overall cortisol (ΣC21) and adrenal androgen secretion; urinary free cortisol and cortisone measured by RIA were summed (UFF+UFE) as an indicator of potentially bioactive free glucocorticoids.</jats:p> </jats:sec> <jats:sec> <jats:title>Main Outcomes:</jats:title> <jats:p>The main outcomes included ATO, age at peak height velocity, age at menarche/voice break, ages at Tanner stage 2 for breast (girls) and genital (boys) development, and pubic hair.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>In girls ΣC21, but not UFF+UFE, was associated with pubertal markers after adjusting for overall adrenal androgen, urinary nitrogen, and body fat. Girls with higher ΣC21 (fourth quartile) reached ATO 0.7 yr (P = 0.01) and menarche 0.9 yr later (P = 0.006) than girls with lower ΣC21 (first quartile). The ΣC21 tended to be also positively associated with age at Tanner stage 2 for breast (P = 0.1), Tanner stage 2 for pubic hair (P = 0.1), and age at peak height velocity (P = 0.06). In boys, neither the ΣC21 nor UFF+UFE was related to pubertal timing.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>An individually higher prepubertal glucocorticoid secretion level, even in physiological range, appears to delay early and late pubertal timing of healthy girls, particularly their onset of pubertal growth spurt and menarche.</jats:p> </jats:sec>