Sex- and gender-based medicine in pediatric nutrition.

Consistent evidence increasingly highlights the significance of integrating sex and gender medicine to ensure a precision approach according to individual patient needs. Gender discrepancies emerge across various areas, even from pediatric age. The importance of recognizing these differences in pediatric nutrition is critical for the development of targeted nutritional strategies and interventions, particularly in cases of associated pathologies, including obesity, metabolic-associated fatty liver disease, eating disorders, and inflammatory bowel disease. The review highlights the biological and sociocultural factors that contribute to different nutritional needs and health outcomes in male and female children. By examining current evidence, we underscore the necessity for precision medicine approaches in pediatric care that consider these sex- and gender-based differences. Moreover, differences in dietary requirements and dietary patterns between males and females are evident, underscoring the need for precise nutrition strategies for a more accurate management of children and adolescents. This approach is essential for improving clinical outcomes and promoting equitable healthcare practices. This review aims to provide an overview of nutrition-related medical conditions exhibiting sex- and gender-specific discrepancies, which might lead to distinct outcomes requiring unique management and prevention strategies. Future research and public health initiatives should address these differences in designing effective lifestyle education programs and nutrition interventions targeting both children and adolescents.

Telemedicine in nutritional management of children with severe neurological impairment: implication for quality of life.

Children with severe neurological impairment (SNI) frequently present feeding problems requiring a close monitoring of their nutritional status. In addition to constant clinical monitoring of body composition and nutritional indexes in these patients, frequent reports of dietary intake and weight gain variations are useful to ensure proper nutritional management. Furthermore, non-oral feeding is often needed to avoid malnutrition or aspiration pneumonia, constantly necessitating medical assistance. Despite their necessity for frequent hospital accesses, these patients' disabilities represent an important obstacle to accessing care, generating anxiety and concern in children and their families. Telemedicine has proven to be a promising instrument for improving pediatric patients' healthcare in several fields. By breaking down geographical and temporal barriers, telehealth may represent a valuable tool to implement in clinical practice, in order to improve patients' outcomes and quality of life. The aim of this narrative review is to provide an overview of the main nutritional issues in children with SNI, the potential implications of telemedicine in their management and the available evidence regarding the effects and benefits of telehealth.

Desensitization of olipudase alfa-induced anaphylaxis in a child with chronic neurovisceral acid sphingomyelinase deficiency.

Olipudase alfa is indicated for the non-central nervous system manifestations of Acid sphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reaction described for this drug. Here, we report the case of a 2-year-old boy affected by chronic neurovisceral ASMD who experienced signs of hypersensitivity reactions to olipudase alfa since the administered dose of 1 mg/kg during dose escalation and a proper anaphylactic reaction during the second administration of the target therapeutic dose of 3 mg/kg. The treatment was stopped for 15 weeks and then a 7-step desensitization protocol with the infused dose of 0.03 mg/kg was applied. Subsequent gradual dose escalation was resumed, successfully reaching the dose of 0.3 mg/kg. Moreover, biochemical, and radiological disease indexes, which were increased during treatment discontinuation, have gradually improved since the restart of treatment. However, at the second administration of the dose of 0.6 mg/kg, the patient experienced another adverse drug reaction with facial urticarial rash and bronchospasm, requiring the administration of adrenaline, methylprednisolone, and inhaled salbutamol. This case report highlights the need to customize the olipudase alfa desensitization protocol according to individual tolerance and raises the issue of achieving the established therapeutic target in the most sensitive children. Synopsis: We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy.

Treatment of Hypertension in Children.

Hypertension is a real problem in children. It shows a tracking behaviour, representing a key risk factor for hypertension, cardiovascular disease, and end-organ failure in adulthood. However, the importance of addressing arterial hypertension in children is not limited to its risk of tracking into adulthood. Thus, early detection and management are crucial. Hypertension may be primary or due to secondary causes, and identification of this distinction is very important for the treatment setting. Importantly, the management of hypertension in children is crucial to prevent the well-known cardiovascular effects in adulthood. As demonstrated in the literature, healthy eating habits, together with regular physical activity, can have a major impact on reducing high blood pressure and preventing organ damage in children and adolescents. However, suppose these are not sufficient to treat hypertension. In that case, if patients are symptomatic and/or have additional metabolic conditions such as obesity, type diabetes mellitus, or chronic kidney disease, anti-hypertensive medication must be started. Recent guidelines have provided clear guidance on the treatment of hypertension and hypertensive crisis in pediatric age. On the other hand, there are currently few specific recommendations on the treatment of isolated nocturnal hypertension and treatment-resistant hypertension. This review aims to summarize the most recent recommendations for the treatment of hypertension and hypertensive crisis in children and the last years' knowledge and experience in treating childhood isolated nocturnal hypertension and resistant hypertension of childhood.

Microbiota gut-brain axis: implications for pediatric-onset leukodystrophies.

Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.

Lung Diseases and Rare Disorders: Is It a Lysosomal Storage Disease? Differential Diagnosis, Pathogenetic Mechanisms and Management.

Pulmonologists may be involved in managing pulmonary diseases in children with complex clinical pictures without a diagnosis. Moreover, they are routinely involved in the multidisciplinary care of children with rare diseases, at baseline and during follow-up, for lung function monitoring. Lysosomal storage diseases (LSDs) are a group of genetic diseases characterised by a specific lysosomal enzyme deficiency. Despite varying pathogen and organ involvement, they are linked by the pathological accumulation of exceeding substrates, leading to cellular toxicity and subsequent organ damage. Less severe forms of LSDs can manifest during childhood or later in life, sometimes being underdiagnosed. Respiratory impairment may stem from different pathogenetic mechanisms, depending on substrate storage in bones, with skeletal deformity and restrictive pattern, in bronchi, with obstructive pattern, in lung interstitium, with altered alveolar gas exchange, and in muscles, with hypotonia. This narrative review aims to outline different pulmonary clinical findings and a diagnostic approach based on key elements for differential diagnosis in some treatable LSDs like Gaucher disease, Acid Sphingomyelinase deficiency, Pompe disease and Mucopolysaccharidosis. Alongside their respiratory clinical aspects, which might overlap, we will describe radiological findings, lung functional patterns and associated symptoms to guide pediatric pulmonologists in differential diagnosis. The second part of the paper will address follow-up and management specifics. Recent evidence suggests that new therapeutic strategies play a substantial role in preventing lung involvement in early-treated patients and enhancing lung function and radiological signs in others. Timely diagnosis, driven by clinical suspicion and diagnostic workup, can help in treating LSDs effectively.

Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison.

Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.

An Adapted Questionnaire Tailored for Assessing the Risk of Vitamin D Deficiency in Children That Is Proving Useful in Guiding Clinical Interventions.

BACKGROUND: The identification of vitamin D (VitD) deficiency in pediatric populations is essential for preventive healthcare. We refined and tested the Evaluation of Deficiency Questionnaire (EVIDENCe-Q) for its utility in detecting VitD insufficiency among children. PATIENTS AND METHODS: We enrolled 201 pediatric patients (aged between 3 and 18 years). Clinical evaluation and serum vitamin D levels were assessed in all subjects. The EVIDENCe-Q was updated to incorporate factors influencing VitD biosynthesis, intake, assimilation, and metabolism, with scores spanning from 0 (optimal) to 36 (poor). RESULTS: We established scores for severe deficiency (<10 mg/dL) at 20, deficiency (<20 mg/dL) at 22, and insufficiency (<30 mg/dL) at 28. A score of 20 or greater was determined as the optimal cut-off for distinguishing VitD deficient from sufficient statuses, as evidenced by ROC curve analysis AUC = 0.7066; SE = 0.0841; sensitivity 100%, 95% CI 0.561-1. The most accurate alignment was seen with VitD insufficiency, defined as 25-OH-D3 < 20 ng/mL. CONCLUSIONS: This study confirms that the EVIDENCe-Q is a valid instrument for assessing the risk of vitamin D deficiency and insufficiency in children. It offers a practical approach for determining the need for clinical intervention and dietary supplementation of VitD in the pediatric population.

Long-term effects of SARS-CoV-2 infection in hospitalized children: findings from an Italian single-center study.

BACKGROUND: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms. METHODS: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge. RESULTS: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta). CONCLUSIONS: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age.

Dietary Inflammatory Potential in Pediatric Diseases: A Narrative Review.

Inflammatory status is one of the main drivers in the development of non-communicable diseases (NCDs). Specific unhealthy dietary patterns and the growing consumption of ultra-processed foods (UPFs) may influence the inflammation process, which negatively modulates the gut microbiota and increases the risk of NCDs. Moreover, several chronic health conditions require special long-term dietary treatment, characterized by altered ratios of the intake of nutrients or by the consumption of disease-specific foods. In this narrative review, we aimed to collect the latest evidence on the pro-inflammatory potential of dietary patterns, foods, and nutrients in children affected by multifactorial diseases but also on the dietetic approaches used as treatment for specific diseases. Considering multifactorial diet-related diseases, the triggering effect of pro-inflammatory diets has been addressed for metabolic syndrome and inflammatory bowel diseases, and the latter for adults only. Future research is required on multiple sclerosis, type 1 diabetes, and pediatric cancer, in which the role of inflammation is emerging. For diseases requiring special diets, the role of single or multiple foods, possibly associated with inflammation, was assessed, but more studies are needed. The evidence collected highlighted the need for health professionals to consider the entire dietary pattern, providing balanced and healthy diets not only to permit the metabolic control of the disease itself, but also to prevent the development of NCDs in adolescence and adulthood. Personalized nutritional approaches, in close collaboration between the hospital, country, and families, must always be promoted together with the development of new methods for the assessment of pro-inflammatory dietary habits in pediatric age and the implementation of telemedicine.

Food Intake and Sleep Disorders in Children and Adolescents with Obesity.

Over the last few decades, numerous scientific studies have investigated the possible association between sleep duration and adiposity during childhood, since it has been reported that sleep deprivation causes a related increase in caloric intake. Even though the underlying pathogenetic mechanisms are still under study and not completely known, the effect of dietetic habits and nutrient intake on sleep quality and patterns has been reported. The aim of this study is to explore the intricate interplay between food intake/diet patterns and pediatric sleep disturbances in children and adolescents with obesity, emphasizing the importance of not underestimating this aspect in the prevention and treatment of this complex disease. Recent evidence supports a high correlation between specific diet patterns and foods with sleep disturbances in children at all ages. Diets rich in fiber, fruit, vegetables, and anti-inflammatory nutrients and low in saturated fats seem to promote better sleep quality. Sleep disturbances are, in turn, risk factors for the development of obesity. Therefore, food strategies should be applied to counteract this harmful process. Unraveling the complex links between dietary habits, sleep patterns, and obesity is essential for developing effective strategies to combat this critical public health issue.

Endocrinological Involvement in Children and Adolescents Affected by COVID-19: A Narrative Review.

Since the advent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increased incidence of several endocrinological anomalies in acute-phase and/or long-term complications has been described. The aim of this review is to provide a broad overview of the available literature regarding changes in the worldwide epidemiology of endocrinological involvement in children since December 2019 and to report the evidence supporting its association with coronavirus disease 2019 (COVID-19). Although little is known regarding the involvement of endocrine organs during COVID-19 in children, the current evidence in adults and epidemiological studies on the pediatric population suggest the presence of a causal association between the virus and endocrinopathies. Untreated transient thyroid dysfunction, sick euthyroid syndrome, nonthyroidal illness syndrome, and hypothalamic-pituitary-adrenal (HPA) axis and central precocious puberty have been observed in children in acute infection and/or during multisystem inflammatory syndrome development. Furthermore, a higher frequency of ketoacidosis at onset in children with a new diagnosis of type 1 diabetes is reported in the literature. Although the direct association between COVID-19 and endocrinological involvement has not been confirmed yet, data on the development of different endocrinopathies in children, both during acute infection and as a result of its long-term complications, have been reported. This information is of primary importance to guide the management of patients with previous or current COVID-19.

Association between Vitamin D Levels, Puberty Timing, and Age at Menarche.

Pubertal development represents the process of physical maturation where an adolescent reaches sexual maturity and attains reproductive function. The effects of vitamin D are mainly mediated by the vitamin D receptor (VDR), which is expressed in almost all body cells, including the ovary and human pituitary gland and animal hypothalamus. Thus, vitamin D has gained great interest as pathogenic factor of pubertal disorders and fertility. This narrative review aimed to provide a broad overview of the available literature regarding the association between vitamin D levels, puberty timing, and age at menarche. A review of the data on the involvement of micronutrient deficiency, as a modifiable cause of pubertal disorders, is important for the prediction and prevention of deficiencies as well as for fertility protection and should be considered a public health priority. Reported data support that vitamin D is a regulator of neuroendocrine and ovarian physiology and, more in detail, a deficiency of vitamin D is involved in altered pubertal timing. Considering the long-term consequences of early pubertal development and early menarche, the detection of modifiable causes is crucial in preventive strategies. Future studies in humans and with an increased scale are needed to elucidate the vitamin D role in sexual maturation and puberty development.

Epigenetic and immunological indicators of IPEX disease in subjects with FOXP3 gene mutation.

BACKGROUND: Forkhead box protein 3 (FOXP3) is the master transcription factor in CD4+CD25hiCD127lo regulatory T (Treg) cells. Mutations in FOXP3 result in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome. Clinical presentation of IPEX syndrome is broader than initially described, challenging the understanding of the disease, its evolution, and treatment choice. OBJECTIVE: We sought to study the type and extent of immunologic abnormalities that remain ill-defined in IPEX, across genetic and clinical heterogeneity. METHODS: We performed Treg-cell-specific epigenetic quantification and immunologic characterization of severe "typical" (n = 6) and "atypical" or asymptomatic (n = 9) patients with IPEX. RESULTS: Increased number of cells with Treg-cell-Specific Demethylated Region demethylation in FOXP3 is a consistent feature in patients with IPEX, with (1) highest values in those with typical IPEX, (2) increased values in subjects with pathogenic FOXP3 but still no symptoms, and (3) gradual increase over the course of disease progression. Large-scale profiling using Luminex identified plasma inflammatory signature of macrophage activation and TH2 polarization, with cytokines previously not associated with IPEX pathology, including CCL22, CCL17, CCL15, and IL-13, and the inflammatory markers TNF-α, IL-1A, IL-8, sFasL, and CXCL9. Similarly, both Treg-cell and Teff compartments, studied by Mass Cytometry by Time-Of-Flight, were skewed toward the TH2 compartment, especially in typical IPEX. CONCLUSIONS: Elevated TSDR-demethylated cells, combined with elevation of plasmatic and cellular markers of a polarized type 2 inflammatory immune response, extends our understanding of IPEX diagnosis and heterogeneity.

Stress and Diabetes Mellitus: Pathogenetic Mechanisms and Clinical Outcome.

Evidence suggests that psychological and physical stress are relevant triggering factors for the onset of type 1 diabetes (T1D) and type 2 diabetes (T2D). The underlying mechanisms involve a complex neuroendocrine structure, involving the central nervous system and the periphery. Psychological stress leads to an increase of serum glucocorticoid concentrations and catecholamines release increasing the insulin need and the insulin resistance. According to the ß-cell stress hypothesis, also causes of increased insulin demand, such as rapid growth, overweight, puberty, low physical activity, trauma, infections, and glucose overload, are potentially relevant factors in development of T1D. It has also been demonstrated that chronic stress and obesity form a vicious circle which leads to a definitive metabolic failure, increasing the risk of developing T2D. In this review, we will provide the most recent data concerning the role of stress in the outcomes of T1D and T2D, with a focus on the role of physical and psychological stress on the onset of T1D.

An update of the consensus statement on insulin resistance in children 2010.

In our modern society, where highly palatable and calorie-rich foods are readily available, and sedentary lifestyle is common among children and adolescents, we face the pandemic of obesity, nonalcoholic fatty liver disease, hypertension, atherosclerosis, and T2D. Insulin resistance (IR) is known to be the main underlying mechanism of all these associated health consequences; therefore, the early detection of IR is fundamental for preventing them.A Consensus Statement, internationally supported by all the major scientific societies in pediatric endocrinology, was published in 2010, providing all the most recent reliable evidence to identify the definition of IR in children, its measurement, its risk factors, and the effective strategies to prevent and treat it. However, the 2010 Consensus concluded that further research was necessary to assess some of the discussed points, in particular the best way to measure insulin sensitivity, standardization of insulin measurements, identification of strong surrogate biomarkers of IR, and the effective role of lifestyle intervention and medications in the prevention and treatment of IR.The aim of this review is to update each point of the consensus with the most recent available studies, with the goal of giving a picture of the current state of the scientific literature regarding IR in children, with a particular regard for issues that are not yet fully clarified.

Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.

Insulin resistance in children.

PURPOSE OF REVIEW: Insulin resistance (IR) is a clinical condition due to the decline in the efficiency of insulin promoting glucose uptake and utilization. The aim of this review is to provide an overview of the current knowledge on IR in children, focusing on its physiopathology, the most appropriate methods of measurement of IR, the assessment of risk factors, the effects of IR in children, and finally giving indications on screening and treatment. RECENT FINDINGS: IR has evolved more and more to be a global public health problem associated with several chronic metabolic diseases. SUMMARY: Detecting a correct measurement method and specific risk predictors, in order to reduce the incidence of IR, represents a challenging goal.

Treatment Options for Lipodystrophy in Children.

Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance, that may lead to severe morbidity and, sometimes, mortality. Therefore, therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Given the evidence of leptin deficiency in lipodystrophy syndromes, leptin replacement therapy has been considered as a treatment option. Long-term studies on the use of therapy with a methionylated analog of human leptin, metreleptin, first on animals and subsequently on human patients, demonstrated enormous improvements of patients' clinical features and metabolic conditions. Recently, metreleptin was approved by Food and Drug Administration (FDA) for the treatment of generalized lipodystrophy and by European Medicines Agency (EMA) for the treatment of both generalized and partial lipodystrophy. However, further research is being conducted for new and different therapeutic agents, especially helpful for the treatment of patients with partial lipodystrophy, as some of them do not have access to metreleptin therapy or show poor response.

Hypertension in Patients with Insulin Resistance: Etiopathogenesis and Management in Children.

Insulin resistance (IR) is a key component in the etiopathogenesis of hypertension (HS) in patients with diabetes mellitus (DM). Several pathways have been found to be involved in this mechanism in recent literature. For the above-mentioned reasons, treatment of HS should be specifically addressed in patients affected by DM. Two relevant recently published guidelines have stressed this concept, giving specific advice in the treatment of HS in children belonging to this group: the European Society of HS guidelines for the management of high blood pressure in children and adolescents and the American Academy of Pediatrics Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Our aim is to summarize the main pathophysiological mechanisms through which IR causes HS and to highlight the specific principles of treatment of HS for children with DM.