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.

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Purpose of review 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. Recent findings 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. Summary 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.

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 COVID19. 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 PDYN in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in 2 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 COVID19, 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.

Although metabolic syndrome (MetS) in children and adolescents is a frequently discussed topic in the literature, uniform guidelines on its definition and treatment are still lacking. Insulin resistance, central obesity, dyslipidaemia, and hypertension are commonly considered the main components of MetS. The first recommended approach to all these pathological conditions in children and adolescents is lifestyle intervention (diet and physical exercise); however, in some selected cases, a pharmacological or surgical treatment might prove useful for the prevention of metabolic and cardiovascular complications. The aim of this review is to present the more recent evidence about the treatment of the major components of MetS in children and adolescents, focussing on the current recommendations concerning lifestyle changes, available drugs, and bariatric surgery.

Anthropologists are frequently required to confirm or exclude the human origin of skeletal remains; DNA and protein radioimmunoassays are useful in confirming the human origin of bone fragments but are not always successful. Histology may be the solution, but the young subadult structure could create misinterpretation. Histological tests were conducted on femur and skull of 31 human subjects. Each sample was observed focusing on presence or absence of fibrous bone, lamellar bone, radial lamellar bone, plexiform bone, reticular pattern, osteon banding, Haversian bone, primary osteons, secondary osteon and osteon fragments. Samples were divided into five age classes; 1 (<1 year), 2 (1-5 years), 3 (6-10 years), 4 (11-15 years) and 5 (16-20 years). Regarding femurs, class 1 presented the following: 87.5% fibrous bone, 37.5% plexiform bone, 12.5% reticular pattern and 12.5% lamellar bone radially oriented. Class 2 showed 37.5% of fibrous bone, 12.5% of reticular pattern and 37.5% of osteon banding. In the higher age classes, the classical human structures, lamellar bone and osteons were frequently visible, except for one case of reticular pattern, generally considered a distinctive non-human structure. The situation appeared different for the skull, where there was a lack of similar information, both in human and non-human. An analysis of the percentage of lamellar bone and osteons was conducted on femur and skull fragments. A trend of increase of primary osteon number and a decrease of the lamellar bone area has been detected in the femur. The present study has therefore shed some light on further pitfalls in species determination of subadult bone.

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.

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