BACKGROUND:Pediatric obesity is associated with early metabolic and kidney alterations, and identifying high-risk children remains challenging. Cystatin C may reflect both kidney and metabolic dysfunction. OBJECTIVES:To assess the relationship between cystatin C and measures of adiposity, insulin resistance (IR), and cardiometabolic risk in children with overweight and obesity. METHODS:In this retrospective cross-sectional study, 169 children with overweight and obesity were analyzed. Anthropometric, blood pressure, kidney (serum creatinine, cystatin C), glucose/insulin, and lipid parameters were collected. Participants were stratified by cystatin C tertiles, and variables were compared across groups. Stepwise regression identified independent predictors of cystatin C. RESULTS:Children in the highest cystatin C tertile had higher SDS-BMI, waist circumference (WC), systolic and diastolic BP SDS, and iCARE index-developed within the Improving Renal Complications in Adolescents With Type 2 Diabetes Through the REsearch (iCARE) Cohort Study as a marker of IR and metabolic risk. They also showed elevated HOMA-IR, fasting glucose-to-insulin ratio (FGIR) and TG:HDL ratio, while glucose excursion did not differ. Stepwise regression identified WC and HOMA-IR as independent predictors of cystatin C. CONCLUSION:Elevated cystatin C in children with overweight and obesity is independently associated with central adiposity and IR, supporting its potential as an integrated early marker of metabolic and kidney risk.

Childhood obesity is an increasingly urgent public health issue with serious long-term implications. Despite greater awareness of its consequences, unhealthy behaviors related to diet, physical inactivity, poor sleep, and body composition persist in the pediatric population. Pediatric outpatient clinics offer a unique opportunity to promote healthy lifestyle habits from an early age, but current educational strategies often fail to engage children and families effectively or to produce lasting changes in behavior. In response to this challenge, we developed an innovative educational tool: the Mediterranean Lifestyle Tridimensional Pyramid. This model integrates three key components of a healthy lifestyle—balanced nutrition, regular physical activity, and adequate sleep—within a single, visually accessible structure. The pyramid also highlights the importance of a healthy muscle-to-fat body composition and encourages a comprehensive understanding of interconnected lifestyle factors. Its tridimensional format visually conveys the concept of health stability, which is achieved when all lifestyle pillars—nutrition, physical activity, and sleep—are built upon solid, interconnected foundations. The tool is designed to improve communication in clinical settings, enhance family engagement, and support the adoption of healthy habits. It is also adaptable for use in schools and community-based health promotion programs. By providing pediatricians and educators with a clear, flexible, and evidence-informed framework, the pyramid facilitates more effective primary and secondary prevention of obesity and related disorders. This approach may contribute to reducing the overall burden of lifestyle-related diseases and support national efforts aimed at improving the health of the pediatric population.

The rs12970134 variant near the melanocortin receptor 4 (MC4-R) has gained relevance suggesting an age dependent phenotypic effect in the induction of obesity in young age. A previous study evaluating 740 Caucasian children has shown this association in prepubertal children older than 8 years. The aim of this study was to assess whether the obesogenic effect of M4CR gene contributed to obesity also in adolescence. After 8 years participants of the original study were contacted and invited to perform an anthropometric evaluation. Out of 35 carriers of the AA risk allele of MC4-R, 12 subjects accepted to participate. Adolescent subjects with the AA risk allele of MC4-R were matched with 24 and 48 subjects, respectively for AG and GG variants. Differences between the three MC4-R genotypes for anthropometric data, for percentage of overweight and obesity and for changes in BMI-SDS over visit have been assessed. At Visit 1 (baseline examination study), the AA risk genotype was confirmed to be associated with higher BMI-SDS (1.3 ± 0.4 vs 0.4 ± 0.1) and waist circumference (66.5 ± 5.8 vs 60.9 ± 7.1) when compared to the GG genotype (p < 0.016 both). At Visit 2 the AA genotype not only was associated with a higher BMI-SDS (1.07 ± 0.5 vs 0.02 ± 0.8) and WC (95.6 ± 13.3 vs 64.9 ± 13.5) when compared to GG genotype, but also when compared to AG genotype (vs 0.5 ± 0.1 and 62.9 ± 10.0, p < 0.016). Whereas AA genotype demonstrated no change of BMI-SDS between visit 1 and visit 2 (p00.32), AG and GG genotype showed a significant reduction (p = 0.01 and 0.001 respectively). Furthermore, a higher percentage of patients were affected by overweight/obesity in the AA genotype compared to AG and GG genotypes (50% vs 20.8% vs 16.5% p = 0.03). This study demonstrates that the rs12970134 variant not only exerts an obesogenic influence in the prepubertal age but remains a major risk factor also during adolescence.

Over the past century of research, it has become increasingly evident that glucagon should no longer be regarded solely as a counter-regulatory hormone to insulin. Its role in the pathophysiology of metabolic disorders—including diabetes, obesity, and non-alcoholic fatty liver disease—appears to be critical. Hyperglucagonemia is a common feature across several metabolic conditions, not only in adults but also in pediatric populations, suggesting that glucagon may represent both a pathogenic factor and a potential therapeutic target in metabolic disease. Accordingly, therapeutic strategies have been developed that either inhibit or enhance glucagon activity, depending on the clinical context, and some of these approaches are being applied in pediatric care as well. This review aims to provide a comprehensive overview of the pathophysiological role of glucagon in metabolic diseases, synthesizing recent findings that support novel hypotheses for the management and prevention of these conditions.

Pediatric obesity is a growing global health concern, associated with metabolic, cardiovascular, and kidney complications. Early identification and intervention are crucial to preventing long-term morbidity. This review examines the epidemiology, pathophysiology, and clinical implications of childhood obesity, focusing on its impact on kidney health. We discuss non-invasive diagnostic tools, including kidney ultrasound, and evidence-based management strategies. Obesity in children is linked to hypertension, insulin resistance, and early signs of kidney dysfunction, including increased kidney echogenicity and hyperfiltration. Ultrasound findings may serve as early markers of kidney involvement, potentially guiding risk stratification and intervention. Addressing pediatric obesity requires a multidisciplinary approach, incorporating lifestyle modifications, medical management, and early detection of organ damage. The aim of this narrative review is to summarize the pathophysiology of pediatric obesity-related kidney damage, current evidence on ultrasound‐based screening, and possible diagnostic techniques. Further research is needed to validate ultrasound as a routine screening tool for obesity-related kidney disease in children.

In a century of research, it has gradually become clear that glucagon should no longer be considered only as a counter-regulatory hormone of insulin accordingly to its role in the physiopathogenesis of metabolic pathologies such as diabetes, obesity and fatty liver appears to be decisive.As hyperglucagonemia represents the common feature of various metabolic pathologies not only in adults but also in pediatric patients, glucagon can be a problem but also a solution in the field of metabolic diseases.In fact, opposing therapeutic strategies have been developed which inhibit or enhance the activity of glucagon depending on the clinical situation and are also applied in pediatric age.This review aims to take stock of the situation on the physiopatogenetic role of glucagon in metabolic pathologies and bring together the dots of recent discoveries leading to the hypothesis of new solutions in the management and prevention ofthesepathologies.

Previously regarded as a movement and posture control agent, the skeletal muscle is now recognized as an endocrine organ that may affect systemic inflammation and metabolic health. The discovery of myokines such as IL-6, released from skeletal muscle in response to physical exercise, is now one of the most recent insights. Myokines are the mediators of the balance between the pro-inflammatory and anti-inflammatory responses. This underscores the muscle function as a determinant of good health and prevention of diseases. Advances in ultrasound technology improved evaluation of muscle thickness, composition, and determining fat distribution. Combining imaging with molecular biology, researchers discovered the complicated interplay between muscle function, cytokine production and general health effects.The production of myokines with exercise showcasing the adaptability of muscles to high-stress conditions and contributing to metabolism and inflammation regulation. These findings have significant implications in order to provide improvement in metabolic and inflammatory diseases.

COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity-related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on children with obesity during the 13 years before and during the COVID-19 pandemic. Data from 741 children with obesity and overweight were retrieved and clustered into seven groups starting from year 2008–2009 until 2020–2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. Children with overweight and obesity in the COVID-19 restriction group did not present increased values of SDS­Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR), and body mass fat were detected in these children (all P < 0.01). Fasting glycaemia, glucose, and insulin excursions were significantly higher compared to pre­ pandemic children (all P < 0.01). Insulin resistance was higher while insulin secretion was lower (all P < 0.01) determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P < 0.002). Furthermore, High-Density Lipoprotein (HDL) cholesterol was significantly lower (P < 0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P = 0.03 and P = 0.02, respectively). COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in children with obesity and overweight. Urgent strategies are needed in order to reverse COVID-19 restriction measures' effects on glucose and insulin metabolism.

OBJECTIVES:We aimed to characterize the effects of COVID-19 Pandemic on 2 h plasma glucose (2 h PG) values after an OGTT postulating a correlation between 2 h PG spectrum and the decline of β-cell function. Particularly, we tried to evaluate the effects on the risk of showing 2 h plasma glucose values in the highest range of normal values in children and adolescent with obesity during COVID-19 Pandemic compared to those evaluated during the 13 years before. SUBJECTS/METHODS:Data from 532 children and adolescents with obesity and overweight (before COVID-19 Pandemic, 209M/262F, 2008-2019; during COVID-19 Pandemic, 40M/21F, 2020-2021) who had undergone a complete evaluation and had performed an OGTT were analyzed. The two groups were further divided into three sub-groups based on the 2 h PG, group 1 (2 h PG < 5.55 mmol/L), group 2 (5.56 < 2 h PG < 6.60 mmol/L), group 3 (6.61 < 2h PG < 7.72 mmol/L), respectively. The prevalence of 2 h PG values distribution in children was evaluated between before and during COVID-19 Pandemic period and the main differences between the two groups 3 of each period were analyzed. RESULTS:A significant difference (P = 0.01) in terms of distribution of the prevalence of 2h PG values was documented between the group before COVID-19 (35.6%, 45.9% and 18.5%) and the group during COVID-19 Pandemic (31.1%, 31.1% and 37.8%). A roughly doble higher prevalence of subjects with pre-IGT was documented in the COVID-19 group. In addition, group 3 of COVID-19 time showed significantly higher values for waist circumference (WC), Waist/Height ratio (WtHR), fasting glucose and HOMA-IR compared to the group 3 of the period before COVID-19 Pandemic (all P < 0.05). CONCLUSIONS:During COVID-19 time a higher percentage of children are in the highest range of normal 2 h PG values which is known to be associated with a significant impairment of β-cell function and insulin sensitivity and have higher risk of developing IGT.

BACKGROUND:Fluid and insulin treatments are the cornerstones of DKA management and indications on dosages are available. However, according to possible confounding factors, relevant data are still required to explain the different insulin dosages adopted at diabetes onset, particularly based upon insulin sensitivity.OBJECTIVE:We aimed to explore whether DKA severity is related to different insulin sensitivity states, thus resulting in different insulin requirement at diabetes onset.METHODS:Retrospective data from hospital records of 62 newly diagnosed children with type 1 diabetes with DKA were analyzed. The population was divided into three groups: severe, moderate, and mild DKA. Anthropometric, laboratory test, insulin, and glucose administration data were analyzed. The Glucose Infusion Rate (GIR), Insulin Infusion Rate (IIR), and GIR/IIR were calculated and used as indexes of insulin sensitivity. The area under the curve (AUC) for insulin and glucose infusion was calculated.RESULTS:Moving among the three groups, IIR decreased while GIR and GIR/IIR increased from severe to mild DKA group (all p < 0.01). A similar trend was documented for AUC-insulin and AUC-glucose as well as AUC-glucose/AUC-insulin ratio. The Spearman correlation showed a negative correlation between pH and both IIR and AUC-Insulin as well as a positive correlation between pH and both GIR/IIR and AUC-glucose/AUC-insulin ratio.CONCLUSIONS:Subjects with severe DKA have a higher insulin requirement compared to those with less severe DKA. Significant differences in terms of insulin sensitivity might be documented according to the severity of DKA, which might result in tailored insulin pH requirement in children with new onset type 1 diabetes.

Background: Type 2 diabetes (T2D) represents just the tip of the iceberg of the complex metabolic alterations associated with obesity and other clinical conditions associated to impaired adipose tissue storage. Summary: Available data have suggested the presence of a continuous spectrum of metabolic alterations developed in the progression from insulin resistance (IR) to T2D, most of which are likely preventable through the early characterization of all the multiple risk factors involved. Therefore, the complete characterization of the natural history of the disease and the major modifiable factors represents a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life. This review will focus on the main components defining the risk of IR and T2D in childhood with a specific focus on the main aspects of treatment options available in children and adolescents. Key messages: Impaired adipose tissue storage documented in obesity results in a continuous spectrum of metabolic alterations ranging from IR to T2DM. These metabolic alterations are mostly likely preventable through the early characterization of all the multiple risk factors involved. The complete characterization of the disease and of the major modifiable factors represent a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life.

Introduction Several studies on obese youths and adults have reported increased hepcidin levels, which seems to be related to metabolic and iron metabolism alterations. The complete mechanisms involved in hepcidin increase remain to be elucidated, and particularly its role in the development of other known complications such as Nonalcoholic Fatty Liver Disease (NAFLD). NAFLD in prepubertal children might be of special interest in understanding the underlying mechanisms. Methods Anthropometric measurements, liver ultrasonography, lipid profile, liver function, oxidative stress, inflammatory state, and iron metabolism were studied in 42 obese prepubertal children and 33 healthy controls. We, therefore, evaluated the presence of possible correlations between Hepcidin and the other metabolic variables, and the possible association between NAFLD and iron metabolism. Results Hepcidin levels were significantly increased in the obese prepubertal children (p=0.001) with significant differences between obese children with and without NAFLD (p=0.01). Blood iron was lower in obese children (p=0.009). In the obese group, a negative correlation between hepcidin and both blood iron levels (p=0.01) and LagPHASE (p=0.02) was found. In addition, a positive association between hepcidin and NAFLD (p=0.03) was detected. Conclusions We suggest that an increase in hepcidin levels may represent an early step in iron metabolism derangements and metabolic alterations, including NAFLD, in prepubertal obese children.

Introduction: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy. Methods: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 +/- 2.3 years; h-SDS: -2.25 +/- -1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment. Results: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern. Discussion/Conclusions: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children.

Recent reports have confirmed higher levels of growth hormone (GH) receptor (GHR) transcripts in malignant melanomas (MM), yet the role of GH in the pathogenesis of MM remains controversial. Although melanocytes appear to be hormonally responsive, the effects of GH on MM cells are less clear. A direct correlation between GH administration and the development of melanoma seems possible. Our study aimed to assess whether GH supplementation in children with growth hormone deficiency (GHD) could induce changes in the melanocytic lesions both from a dimensional and dermoscopic point of view. The study population consisted of 14 patients sorted into two groups. The experimental group consisted of seven GHD pediatric patients who underwent dermatological examination with epiluminescence through the use of digital video recording of all melanocytic lesions before and after 12 months of GH supplementation, whilst the control group consisted of seven healthy pediatric patients matched for age, sex and phototype. All patients were evaluated according to auxological and dermatological features. A total of 225 melanocytic lesions were examined in the experimental group and 236 in the control group. Our study shows a significant increase in the mean size values of the lesions in the study group but not in the control group. Increases in the dermoscopic ABCD Score and in BMI correlated to an increase in the size of the melanocytic lesions and the dermoscopic parameters. The increase in SDS Height correlated with ABCD Score changes and with dermoscopic score structures. No differences were found compared to the control group. Dimensional/structural modifications in melanocytic lesions of patients treated with GH were closely related to weight and statural growth and can be considered a normal physiological process induced by GH supplementation.