Epigenome-Wide Meta-analysis Reveals Associations Between Dietary Glycemic Index and Glycemic Load and DNA Methylation in Children and Adolescents of Different Body Sizes.

OBJECTIVE: Dietary glycemic index (GI) and glycemic load (GL) are associated with cardiometabolic health in children and adolescents, with potential distinct effects in people with increased BMI. DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta-analyses of epigenome-wide association studies (EWAS) between dietary GI and GL and blood DNAm of children and adolescents. RESEARCH DESIGN AND METHODS: We calculated dietary GI and GL and performed EWAS in children and adolescents (age range: 4.5-17 years) from six cohorts (N = 1,187). We performed stratified analyses of participants with normal weight (n = 801) or overweight or obesity (n = 386). We performed look-ups for the identified cytosine-phosphate-guanine (CpG) sites (false discovery rate [FDR] <0.05) with tissue-specific gene expression of 832 blood and 223 subcutaneous adipose tissue samples from children and adolescents. RESULTS: Dietary GL was positively associated with DNAm of cg20274553 (FDR <0.05), annotated to WDR27. Several CpGs were identified in the normal-weight (GI: 85; GL: 17) and overweight or obese (GI: 136; GL: 298; FDR <0.05) strata, and none overlapped between strata. In participants with overweight or obesity, identified CpGs were related to RNA expression of genes associated with impaired metabolism (e.g., FRAT1, CSF3). CONCLUSIONS: We identified 537 associations between dietary GI and GL and blood DNAm, mainly in children and adolescents with overweight or obesity. High-GI and/or -GL diets may influence epigenetic gene regulation and thereby promote metabolic derangements in young people with increased BMI.

Dietary fiber and growth, iron status and bowel function in children 0-5 years old: a systematic review.

Background: While dietary fiber intake is low in many children, the current trend to plant-based diets is associated with higher fiber intake in children raised on these diets. As older reports indicate that diets providing high fiber intake in children 0-5 years may affect growth, iron status and bowel function, we summarized the available evidence in this systematic review. Objective: To identify, critically appraise, and synthesize evidence on the effect of high fiber intake on growth, iron and bowel function in children 0-5 years, with relevance to the Nordic and Baltic countries. Methods: Following a pre-registered protocol, we searched MEDLINE, EMBASE, Cochrane Central of Controlled Trials, and Scopus for clinical trials and prospective cohort studies published until November 2021. Two reviewers independently screened retrieved literature, extracted relevant data, and performed risk of bias assessment. Outcomes were growth, iron metabolism and bowel function in children 0-5 years. We narratively described findings from studies that met inclusion criteria. Results: From 5,644 identified records, five articles met the inclusion criteria. Two RCTs had an overall moderate risk of bias, while the three observational studies had serious risk. Overall, we found no robust association between high intake of dietary fiber and growth. In the RCTs, higher intake of fiber had a positive effect on bowel movements and constipation. No studies on fiber intake and iron status were identified.The certainty of the overall evidence was inconclusive for growth and bowel function, while no assessment was made for iron status. Conclusion: We found no clear association between high intake of dietary fiber and growth or bowel function in young children living in affluent countries, albeit with only a limited number of studies. There is a lack of studies investigating health effects of high fiber intake in small children.

Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis.

Objectives: We aimed to systematically review studies and evaluate the strength of the evidence on nuts/seeds consumption and cardiometabolic diseases and their risk factors among adults. Methods: A protocol was pre-registered in PROSPERO (CRD42021270554). We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to September 20, 2021 for prospective cohort studies and ≥12-week randomized controlled trials (RCTs). Main outcomes were cardiovascular disease (CVD), coronary heart disease (CHD), stroke and type 2 diabetes (T2D), secondary total-/low density lipoprotein (LDL)-cholesterol, blood pressure and glycaemic markers. Data extraction and risk of bias (RoB) assessments (using RoB 2.0 and RoB-NObS) were performed in duplicate. Effect sizes were pooled using random-effects meta-analyses and expressed as relative risk (RR) or weighted mean differences with 95% confidence intervals (CI); heterogeneity quantified as I 2. One-stage dose-response analyses assessed the linear and non-linear associations with CVD, CHD, stroke and T2D. The strength of evidence was classified per the World Cancer Research Fund criteria. Results: After screening 23,244 references, we included 42 papers from cohort studies (28 unique cohorts, 1,890,573 participants) and 18 RCTs (2,266 participants). In the cohorts, mainly populations with low consumption, high versus low total nuts/seeds consumption was inversely associated with total CVD (RR 0.81; 95% CI 0.75, 0.86; I 2 = 67%), CVD mortality (0.77; 0.72, 0.82; I 2 = 59.3%), CHD (0.82; 0.76, 0.89; I 2 = 64%), CHD mortality (0.75; 0.65, 0.87; I 2 = 66.9%) and non-fatal CHD (0.85; 0.75, 0.96; I 2 = 62.2%). According to the non-linear dose-response analyses, consumption of 30 g/day of total nuts/seeds was associated with RRs of similar magnitude. For stroke and T2D the summary RR for high versus low intake was 0.91 (95% CI 0.85, 0.97; I 2 = 24.8%) and 0.95 (0.75, 1.21; I 2 = 82.2%). Intake of nuts (median ~50 g/day) lowered total (-0.15 mmol/L; -0.22, -0.08; I 2 = 31.2%) and LDL-cholesterol (-0.13 mmol/L; -0.21, -0.05; I 2 = 68.6%), but not blood pressure. Findings on fasting glucose, HbA1c and insulin resistance were conflicting. The results were robust to sensitivity and subgroup analyses. We rated the associations between nuts/seeds and both CVD and CHD as probable. There was limited but suggestive evidence for no association with stroke. No conclusion could be made for T2D. Conclusion: There is a probable relationship between consumption of nuts/seeds and lower risk of CVD, mostly driven by CHD, possibly in part through effects on blood lipids. More research on stroke and T2D may affect the conclusions. The evidence of specific nuts should be further investigated.

Parent-child agreement in different domains of child behavior and health.

AIM: The present study aimed to investigate and compare parent-child agreement in different domains of child health and behavior. METHODS: Data were collected between 2011 and 2019 within the framework of the LIFE Child study (Germany). Different subgroups of 10- to 12-year-old children and their parents (n (max) = 692) completed questionnaires on several health behaviors (diet, media use, physical activity, sleep), parameters of health (behavioral strengths and difficulties, psychosomatic complaints), and school grades. Agreement between child and parent reports was evaluated using weighted kappa coefficients. Furthermore, the frequencies of different types of (dis)agreement (parent report > child report, same response, child report > parent report) were assessed and checked for associations with child or parent gender. RESULTS: Agreement between child and parent reports varied from low to almost perfect, with the greatest levels of agreement for school grades and organized physical activity, and the lowest for dizziness, sleep duration, and the consumption of potatoes. Child gender had no significant effect on parent-child agreement. In contrast, the findings suggest that parent gender had some effect on agreement levels, with higher agreement for certain psychosomatic complaints when parent reports were completed by the mother, and higher agreement for white bread consumption if they were completed by the father. For some of the questionnaire items (especially those relating to behavioral difficulties and psychosomatic complaints, but also to the consumption of individual food products and mobile phone use), the type of (dis)agreement differed depending on child or parent gender. CONCLUSIONS: The findings suggest that the perceptions and reporting strategies of children and their parents can diverge considerably, in particular for behavior that is not easily observable or measurable.

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence.

Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

Diabetes screening in overweight and obese children and adolescents: choosing the right test.

Type 2 diabetes can occur without any symptoms, and health problems associated with the disease are serious. Screening tests allowing an early diagnosis are desirable. However, optimal screening tests for diabetes in obese youth are discussed controversially. We performed an observational multicenter analysis including 4848 (2668 female) overweight and obese children aged 7 to 17 years without previously known diabetes. Using HbA1c and OGTT as diagnostic criteria, 2.4% (n = 115, 55 female) could be classified as having diabetes. Within this group, 68.7% had HbA1c levels ≥48 mmol/mol (≥6.5%). FPG ≥126 mg/dl (≥7.0 mmol/l) and/or 2-h glucose levels ≥200 mg/dl (≥11.1 mmol/l) were found in 46.1%. Out of the 115 cases fulfilling the OGTT and/or HbA1c criteria for diabetes, diabetes was confirmed in 43.5%. For FPG, the ROC analysis revealed an optimal threshold of 98 mg/dl (5.4 mmol/l) (sensitivity 70%, specificity 88%). For HbA1c, the best cut-off value was 42 mmol/mol (6.0%) (sensitivity 94%, specificity 93%). CONCLUSIONS: HbA1c seems to be more reliable than OGTT for diabetes screening in overweight and obese children and adolescents. The optimal HbA1c threshold for identifying patients with diabetes was found to be 42 mmol/mol (6.0%). What is Known: • The prevalence of obesity is increasing and health problems related to type 2 DM can be serious. However, an optimal screening test for diabetes in obese youth seems to be controversial in the literature. What is New: • In our study, the ROC analysis revealed for FPG an optimal threshold of 98 mg/dl (5.4 mmol/l, sensitivity 70%, specificity 88%) and for HbA1c a best cut-off value of 42 mmol/mol (6.0%, sensitivity 94%, specificity 93%) to detect diabetes. Thus, in overweight and obese children and adolescents, HbA1c seems to be a more reliable screening tool than OGTT.