Insulin Resistance in Children Tagi, Veronica Maria; Giannini, Cosimo; Chiarelli, Francesco
Frontiers in endocrinology,
06/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
Insulin resistance (IR) is a pathological condition strongly associated with obesity. However, corticosteroids or growth hormone therapy and genetic diseases may affect insulin sensitivity lifelong. ...In obese children and adolescents of any age there is an evident association between IR and an increased prevalence of type 2 diabetes (T2D) and other elements contributing to the metabolic syndrome, leading to a higher cardiovascular risk. Therefore, early diagnosis and interventions in the attempt to prevent T2D when glycemia values are still normal is fundamental. The gold standard technique used to evaluate IR is the hyperinsulinemic euglycemic clamp, however it is costly and difficult to perform in clinical and research sets. Therefore, several surrogate markers have been proposed. Although the treatment of insulin resistance in children is firstly targeted to lifestyle interventions, in selected cases the integration of a pharmacological intervention might be taken into consideration. The aim of this review is to present the current knowledge on IR in children, starting with an outline of the recent evidences about the congenital forms of deficiency in insulin functioning and therefore focusing on the physiopathology of IR, its appropriate measurement, consequences, treatment options and prevention strategies.
Cardiovascular diseases are the main causes of death and health costs in developed countries. Although cardiovascular diseases are thought to affect only adulthood, the underlying process of ...atherosclerosis begins in the first decade of life. Epidemiological studies show that severity of atherosclerosis depends both on the number and intensity of risk factors. Early detection of cardiovascular risk in childhood is the most powerful tool to prevent cardiovascular accidents in adulthood and possibly reduce its consequent burden for the future.A large amount of cardiovascular risk factors is already detectable in childhood and include non-modifiable elements, among which genetic factors and congenital heart diseases, and modifiable elements, which depend on environmental effects (e.g. lifestyle and nutrition). Regardless of the possibility to intervene on these factors, an early diagnosis is fundamental to ensure an optimal life expectancy in adulthood. The most important cardiovascular risk factors in the paediatric age and adolescence are excess weight, arterial hypertension, glucose metabolism and lipid metabolism alterations.In this review we will discuss the main risk factors strictly correlated with cardiac and vessels diseases, focusing on their pathogenesis, diagnosis, and treatments.
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.
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.
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.
Familial hypercholesterolemia is a common autosomal hereditary disorder characterized by elevated concentrations of low-density lipoprotein cholesterol and the development of premature ...atherosclerosis and cardiovascular disease. Early diagnosis, as well as prompt and aggressive treatment, are fundamental steps to prevent cardiovascular complications and a high rate of premature mortality in children and adolescents. Clinics and genetics are the two main aspects on which diagnosis is based. Widespread screening programs are a respectable option for the early detection of familial hypercholesterolemia. Different types of screening have been proposed so far; however, the optimal screening program has not yet been found. The treatment approach for both heterozygous and homozygous familial hypercholesterolemia in the pediatric population is multidisciplinary, including lifestyle modifications, standard lipid-lowering medications, and novel pharmacological agents. The latter show promising results, especially for patients who experience intolerance to other treatment or present with more severe conditions. Our purpose is to focus on the importance of the early detection of familial hypercholesterolemia, and to highlight the best therapeutic strategies, including the recent approaches based on current clinical evidence, that need to be adopted from the earliest stages of life.
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.
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.
It is well known that obesity represents the main modifiable risk factor for insulin resistance in children and adolescents; obesity-induced insulin resistance in children is the most important risk ...factor for developing cardiovascular diseases and type 2 diabetes in adulthood. The mechanisms through which obesity causes insulin resistance are complex and not completely known to date.
In children, global adiposity is the main factor determining insulin resistance. Excessive fatty acids play a determinant role in the pathogenesis of insulin resistance in obese children, inducing an increased production of acetyl-CoA in the liver and enhancing inflammation in adipose tissue. The aetiology of insulin resistance in polycystic ovary syndrome is multifactorial and still debated.
The aim of this review is to present an updated frame and new insights of the numerous pathways involved in the development of insulin resistance in obese patients, focusing on the peculiarities of children and adolescents. Improving the knowledge of mechanisms through which obesity leads to insulin resistance is fundamental in order to recommend particular follow-up and possible treatment to specific categories of obese children and adolescents.
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.