-
1.
Breakfast Skipping, Weight, Cardiometabolic Risk, and Nutrition Quality in Children and Adolescents: A Systematic Review of Randomized Controlled and Intervention Longitudinal Trials.
Ricotti, R, Caputo, M, Monzani, A, Pigni, S, Antoniotti, V, Bellone, S, Prodam, F
Nutrients. 2021;(10)
Abstract
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 included. 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 insight 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.
-
2.
Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial.
Solito, A, Bozzi Cionci, N, Calgaro, M, Caputo, M, Vannini, L, Hasballa, I, Archero, F, Giglione, E, Ricotti, R, Walker, GE, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4585-4594
Abstract
BACKGROUND & AIMS Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. METHODS Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6-18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. RESULTS All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0-0.03) and during OGTT (ISI, 0.654 CI95%-0.11-1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. CONCLUSION An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. TRIAL REGISTRATION NCT03261466.
-
3.
Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer.
Perrone, E, Lopez, S, Zeybek, B, Bellone, S, Bonazzoli, E, Pelligra, S, Zammataro, L, Manzano, A, Manara, P, Bianchi, A, et al
Frontiers in oncology. 2020;:118
Abstract
Background: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Sacituzumab govitecan (SG) is a novel antibody-drug-conjugate (ADC) targeting trophoblast-antigen-2 (Trop-2), a cell surface glycoprotein highly expressed in many epithelial tumors, to deliver SN-38, the active metabolite of irinotecan. This study aimed to evaluate Trop-2 expression in EOC tissues and the preclinical activity of SG against primary EOC cell lines and xenografts. Methods: Trop-2 expression was assessed in 90 formalin-fixed-paraffin-embedded tumors and nine primary tumor cell lines by immunohistochemistry (IHC) and flow cytometry, respectively. Trop-2 expression and cell viability after exposure to SG in primary tumor cell lines, non-targeting control ADC, and SG-parental antibody hRS7 were evaluated using flow-cytometry-based-assays. Antibody-dependent-cell-cytotoxicity (ADCC) against Trop-2+ and Trop-2- EOC cell lines was tested in vitro using 4 h Chromium-release-assays. In vivo activity of SG was evaluated against Trop-2+ EOC xenografts. Results: Moderate-to-strong staining was seen in 47% (42/90) of ovarian tumors by IHC while 89% (8/9) of the primary EOC cell lines overexpressed Trop-2 by flow cytometry. EOC Trop-2+ were significantly more sensitive to SG compared to control ADC (p < 0.05). Both SG and hRS7 mediated high ADCC activity against Trop-2+ cell lines. SG also induced significant bystander killing of Trop-2- tumor cells admixed with Trop-2+ EOC cells. In in vivo experiments SG treatment demonstrated impressive anti-tumor activity against chemotherapy-resistant EOC xenografts. Conclusion: SG demonstrates remarkable preclinical activity against biologically aggressive and chemotherapy-resistant EOC cell lines and a significant bystander effect against EOC cell lines with heterogenous Trop-2 expression. Clinical trials are warranted.
-
4.
Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics.
Valerio, G, Maffeis, C, Saggese, G, Ambruzzi, MA, Balsamo, A, Bellone, S, Bergamini, M, Bernasconi, S, Bona, G, Calcaterra, V, et al
Italian journal of pediatrics. 2018;(1):88
Abstract
The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.
-
5.
The Association of Bifidobacterium breve BR03 and B632 is Effective to Prevent Colics in Bottle-fed Infants: A Pilot, Controlled, Randomized, and Double-Blind Study.
Giglione, E, Prodam, F, Bellone, S, Monticone, S, Beux, S, Marolda, A, Pagani, A, Di Gioia, D, Del Piano, M, Mogna, G, et al
Journal of clinical gastroenterology. 2016;:S164-S167
Abstract
GOALS To assess the effectiveness of Bifidobacterium breve B632 and BR03 association in the reduction of infants crying over time. The second endpoint was to observe the effect of the same strains on daily evacuations and on the number of regurgitations and vomits. BACKGROUND Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause. An altered intestinal microbiota composition in the very first months may induce intestinal colics in infants. Thus far, no treatment is really effective for this problem, but recent literature shows an increasing attention toward probiotics. STUDY A total of 83 subjects were enrolled, 60 breastfed infants and 23 bottle-fed infants. Sixty of them carried out the study: 29 infants were given probiotics, whereas 31 placebo. During the 90 days of the study, parents were asked to give 5 drops of active product (10 viable cells/strain) or placebo and to daily take note of: minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits. RESULTS No significant differences were detected in the infants treated with probiotics, compared with placebo group (P=0.75). The analysis of the 3 months of treatment demonstrated that during the third month, the probiotic group cried 12.14 minutes on average and the placebo cried 46.65 minutes. This difference is statistically significant (P=0.016). CONCLUSIONS The evidence of the usefulness of some probiotic strains in the treatment and prevention of infant colics is growing, and therefore their use in clinical practice is spreading.
-
6.
Adiponectin oligomers are similarly distributed in adequate-for-gestational-age obese children irrespective of feeding in their first year.
Prodam, F, Roccio, M, Trovato, L, Ricotti, R, Moia, S, Giglione, E, Petri, A, Walker, GE, Bellone, S, Bona, G
Pediatric research. 2015;(6):808-13
Abstract
BACKGROUND Nutrition and growth in early postnatal life have a role in future diseases. Our aim was to investigate adiponectin oligomers in adequate-for-gestational-age obese children with respect to type and duration of feeding in the first year of life. METHODS Adiponectin oligomers and cardiometabolic risk factors were measured in 113 adequate-for-gestational-age obese children, divided into group A (prolonged breast feeding, >6 mo), group B (short breast feeding, 1-6 mo), and group C (formula feeding from birth). RESULTS All the parameters were similar among the groups. Adiponectin oligomers did not correlate with gestational age, months of breast feeding, and time of weaning. Total and high-molecular weight adiponectin were differently distributed across gender and pubertal stages (P < 0.02), being lower in males from the start of puberty. Prepregnancy BMI and at the end of the pregnancy were negatively associated (P < 0.04) with total and medium-molecular weight adiponectin in female and male offspring, respectively. CONCLUSIONS Adiponectin oligomers and metabolic characteristics are similarly distributed in adequate-for-gestational-age obese children, irrespective of the type and duration of the feeding in the first year of life. Gender and mother's BMI in pregnancy are contributors to adiponectin regulation. Further studies will explain whether breastfeeding protects against metabolic impairment later in life.
-
7.
Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.
Prodam, F, Savastio, S, Genoni, G, Babu, D, Giordano, M, Ricotti, R, Aimaretti, G, Bona, G, Bellone, S
PloS one. 2014;(1):e87157
Abstract
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%β, 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, HOMAβ 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, HOMAβ, 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-β 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.
-
8.
Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents.
Prodam, F, Monzani, A, Ricotti, R, Marolda, A, Bellone, S, Aimaretti, G, Roccio, M, Bona, G
The Journal of clinical endocrinology and metabolism. 2014;(5):1556-68
Abstract
OBJECTIVE Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence. METHODS We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included. RESULTS AND CONCLUSIONS Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.
-
9.
Lipid profile and nutritional intake in children and adolescents with Type 1 diabetes improve after a structured dietician training to a Mediterranean-style diet.
Cadario, F, Prodam, F, Pasqualicchio, S, Bellone, S, Bonsignori, I, Demarchi, I, Monzani, A, Bona, G
Journal of endocrinological investigation. 2012;(2):160-8
Abstract
AIM: To evaluate if nutritional intakes and lipid profile fulfill international guidelines and recommendations before and after a structured dietician training to a Mediterranean- style diet in an Italian pediatric population with Type 1 diabetes. METHODS A 6-month prospective cohort study. Baseline and after-intervention nutritional intakes, lipid profile, glycated hemoglobin (HbA(1c)), and clinical parameters of 96 children and adolescents with Type 1 diabetes were assessed. A comparative computerized system which was approved and validated by the Italian Diabetologist Association was used to define the amounts of nutrients. RESULTS At baseline mean daily dietary intakes of carbohydrates, proteins, and lipids were respectively (mean ± SEM) 51.8 ± 0.5, 15.9 ± 0.2, 33.8 ± 0.6%, with a contribution of cholesterol of 248.7 ± 12.5 mg/day. Fiber assumption was 18.0 ± 0.4 g/day. The 64.5% and 29.1% (p<0.0001) of subjects had at least one lipid parameter higher than 75(th) and 95(th) percentiles, respectively, of selected cut points (American Diabetes Association guidelines for total and LDL-cholesterol and American Academy of Pediatrics standards for HDL-cholesterol and triglycerides). Six months after the dietician intervention, dietary lipids and cholesterol decreased (p<0.0001) while fibers (p<0.0001) increased. LDL-cholesterol, non-HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios significantly decreased (p<0.001) with a reduction of rate of subjects with at least one pathological lipid parameter (p<0.01) independently by weight and glucose control. CONCLUSIONS Italian pediatric subjects with Type 1 diabetes present a balanced diet with exception of lipids intake and a suboptimal lipid profile. A structured dietician training to a Mediterranean-style diet improves the quality of nutrient intakes being followed by a reduction of LDL-cholesterol, non- HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios.
-
10.
Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone Sufficient and GH Deficient Children.
Prodam, F, Genoni, G, Bellone, S, Longhi, S, Agarla, V, Bona, G, Radetti, G
International journal of endocrinology and metabolism. 2012;(2):470-4
Abstract
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-insulin-like growth factor (GH-IGF)-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 ± SEM], 10.7 ± 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean ± SEM], 10.3 ± 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.