Breakfast skipping, weight, cardiometabolic risk, and nutrition quality in children and adolescents: A systematic review of randomized controlled and intervention longitudinal trials

Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months. We searched relevant databases (2000–2021) and identified 584 articles, of which 16 were suitable for inclusion. Overall, 50,066 children and adolescents were in-cluded. No studies analyzed cardiometabolic features. Interventions were efficacious in reducing breakfast skipping prevalence when multi-level approaches were used. Two longitudinal studies reported a high prevalence of OW/OB in breakfast skippers, whereas RCTs had negligible effects. Ten studies reported a lower-quality dietary intake in breakfast skippers. This review provides in-sight into the fact that breakfast skipping is a modifiable marker of the risk of OW/OB and unhealthy nutritional habits in children and adolescents. Further long-term multi-level intervention studies are needed to investigate the relationship between breakfast, nutrition quality, chronotypes, and cardiometabolic risk in youths

The atrophic effect of 1,25(Oh)2 vitamin d3 (calcitriol) on c2c12 myotubes depends on oxidative stress

Dysfunctional mitochondrial metabolism has been linked to skeletal muscle loss in several physio-pathological states. Although it has been reported that vitamin D (VD) supports cellular redox homeostasis by maintaining normal mitochondrial functions, and VD deficiency often occurs in conditions associated with skeletal muscle loss, the efficacy of VD supplementation to overcome muscle wasting is debated. Investigations on the direct effects of VD metabolites on skeletal muscle using C2C12 myotubes have revealed an unexpected pro-atrophic activity of calcitriol (1,25VD), while its upstream metabolites cholecalciferol (VD3) and calcidiol (25VD) have anti-atrophic effects. Here, we investigated if the atrophic effects of 1,25VD on myotubes depend on its activity on mitochondrial metabolism. The impact of 1,25VD and its upstream metabolites VD3 and 25VD on mitochondria dynamics and the activity of C2C12 myotubes was evaluated by measuring mitochondrial content, architecture, metabolism, and reactive oxygen species (ROS) production. We found that 1,25VD induces atrophy through protein kinase C (PKC)-mediated ROS production, mainly of extramito-chondrial origin. Consistent with this, cotreatment with the antioxidant N-acetylcysteine (NAC), but not with the mitochondria-specific antioxidant mitoTEMPO, was sufficient to blunt the atrophic activity of 1,25VD. In contrast, VD3 and 25VD have antioxidant properties, suggesting that the efficacy of VD supplementation might result from the balance between atrophic pro-oxidant (1,25VD) and protective antioxidant (VD3 and 25VD) metabolites

GH therapy in adult GH deficiency: a review of treatment schedules and the evidence for low starting doses.

Recombinant human growth hormone (GH) has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing regimens were effective but resulted in supraphysiological levels of insulin-like growth factor-I (IGF-I) and increased incidence of side effects. Current practice has moved towards individualized regimens, starting with low GH doses and gradually titrating the dose according to the level of serum IGF-I to achieve an optimal dose. Here we present the evidence supporting the dosing recommendations of current guidelines and consider factors affecting dose responsiveness and parameters of treatment response. The published data discussed here lend support for the use of low GH dosing regimens in adult GHD. The range of doses defined as 'low dose' in the studies discussed here (~1-4 mg/week) is in accordance with those recommended in current guidelines and encompasses the dose range recommended by product labels

Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children.

Background: The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone\u2013insulin-like growth factor (GH\u2013IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate. Objectives: To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children Patients and Methods: Ten GHD (male/female [M/F], 6/4; age [mean \ub1 SEM], 10.7 \ub1 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean \ub1 SEM], 10.3 \ub1 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min. Results: Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion. Conclusions: Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action

A long contiguous stretch of homozygosity disclosed a novel stag3 biallelic pathogenic variant causing primary ovarian insufficiency: A case report and review of the literature

Primary ovarian insufficiency (POI) refers to an etiologically heterogeneous disorder characterized by hypergonadotropic hypogonadism that represents a major cause of infertility in women under 40 years of age. Most cases are apparently sporadic, but about 10–15% have an affected first-degree relative, indicating a genetic etiology. Pathogenic variations in genes involved in development, meiosis and hormonal signaling have been detected in the hereditary form of the disorder. However, most cases of POI remain unsolved even after exhaustive investigation. A 19-year-old Senegalese female affected by non-syndromic POI presented with primary amenorrhoea and answered well to the hormonal induction of puberty. In order to investigate the presence of a genetic defect, aCGH-SNP analysis was performed. A 13.5 Mb long contiguous stretch of homozygosity (LCSH) was identified on chromosome 7q21.13-q22.1 where the exome sequencing revealed a novel homozygous 4-bp deletion (c.3381_3384delAGAA) in STAG3. Pathogenic variants in this gene, encoding for a meiosis-specific protein, have been previously reported as the cause of POI in only eight families and recently as the cause of infertility in a male. The here-identified mutation leads to the truncation of the last 55 amino acids, confirming the important role in meiosis of the STAG3 C-terminal domain

Effects of Growth Hormone (GH) Therapy Withdrawal on Glucose Metabolism in Not Confirmed GH Deficient Adolescents at Final Height.

CONTEXT OBJECTIVE: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR). DESIGN SETTING: We performed a longitudinal study (1 year) in a tertiary care center. METHODS: 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%\u3b2, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR. RESULTS: In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMA\u3b2 and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMA\u3b2, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01). CONCLUSIONS: In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-\u3b2 and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view

Is Caloric Restriction Associated with Better Healthy Aging Outcomes? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Global dietary patterns have gradually shifted toward a 'western type' with progressive increases in rates of metabolic imbalance. Recently, animal and human studies have revealed positive effects of caloric restriction (CR) on many health domains, giving new knowledge for prevention of ill and health promotion; Methods: We conducted a systematic review (SR) of randomized controlled trials (RCTs) investigating the role of CR on health status in adults. A meta-analysis was performed on anthropometric, cardiovascular and metabolic outcomes; Results: A total of 29 articles were retrieved including data from eight RCTs. All included RCTs were at low risk for performance bias related to objective outcomes. Collectively, articles included 704 subjects. Among the 334 subjects subjected to CR, the compliance with the intervention appeared generally high. Meta-analyses proved benefit of CR on reduction of body weight, BMI, fat mass, total cholesterol, while a minor impact was shown for LDL, fasting glucose and insulin levels. No effect emerged for HDL and blood pressure after CR. Data were insufficient for other hormone variables in relation to meta-analysis of CR effects; Conclusion: CR is a nutritional pattern linked to improved cardiometabolic status. However, evidence is limited on the multidimensional aspects of health and requires more studies of high quality to identify the precise impact of CR on health status and longevity

Adherence to the Mediterranean Diet Is Associated with Better Metabolic Features in Youths with Type 1 Diabetes

Our aim was to evaluate adherence to the Mediterranean diet (MedDiet) among children and adolescents with type 1 diabetes (T1D) in relation to metabolic control. Adherence to the MedDiet was assessed with the Mediterranean Diet Quality Index (KIDMED)questionnaire and physical activity by the International Physical Activity Questionnaire for Adolescent (IPAQ-A) on 65 subjects (32 males, 9–18 years) with T1D. Clinical and metabolic evaluation was performed (standardized body mass index(BMI-SDS), hemoglobin A1C (HbA1c), continuous glucose monitoring metrics when present, blood pressure, lipid profile). Parental characteristics (age, body mass index (BMI), socio-economic status) were reported. The adherence to the MedDiet was poor in 12.3%, average in 58.6%, and high in 29.1% of the subjects. Furthermore, 23.4% of patients were overweight/obese. The most impacting factors on BMI-SDS were skipping breakfast and their father’s BMI. HbA1c and time in range % were positively associated with sweets and fish intake, respectively. Additionally, the father’s socio-economic status (SES) and mother’s age were associated with glucose control. Blood pressure was associated with travelling to school in vehicles, extra-virgin olive oil intake and milk/dairy consumption at breakfast. The promotion of the MedDiet, mainly having a healthy breakfast, is a good strategy to include in the management of T1D to improve glucose and metabolic control. This research is valuable for parents to obtain the best results for their children with T1D

Transsphenoidal surgery for pituitary adenomas: early results from a single center

To evaluate early results of transsphenoidal surgery for pituitary adenomas