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.

Dysregulation of several metabolite pathways, including branched-chain amino acids (BCAAs), are associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and insulin resistance in adults, while studies in youth reported conflicting results. We explored whether, independently of obesity and insulin resistance, obese adolescents with NAFLD display a metabolomic signature consistent with disturbances in amino acid and lipid metabolism. A total of 180 plasma metabolites were measured by a targeted metabolomic approach in 78 obese adolescents with (n = 30) or without (n = 48) NAFLD assessed by magnetic resonance imaging (MRI). All subjects underwent an oral glucose tolerance test and subsets of patients underwent a two-step hyperinsulinemic-euglycemic clamp and/or a second MRI after a 2.2 ± 0.8-year follow-up. Adolescents with NAFLD had higher plasma levels of valine (p = 0.02), isoleucine (p = 0.03), tryptophan (p = 0.02), and lysine (p = 0.02) after adjustment for confounding factors. Circulating BCAAs were negatively correlated with peripheral and hepatic insulin sensitivity. Furthermore, higher baseline valine levels predicted an increase in hepatic fat content (HFF) at follow-up (p = 0.01). These results indicate that a dysregulation of BCAA metabolism characterizes obese adolescents with NAFLD independently of obesity and insulin resistance and predict an increase in hepatic fat content over time.

Type 1 diabetes mellitus (T1DM) and other chronic diseases in children are well known to adversely affect linear growth and pubertal development. In the years immediately following the introduction of insulin therapy, short stature was consistently reported in children with T1DM. However, over the past 50 years significant improvement in the prognosis for growth and final height in children with diabetes has been achieved. Although pre-pubertal and post-pubertal growth are important phases in growth, puberty and its related hormonal changes represent a critical phase for growth gain and final height particularly in patients with T1DM. Growth impairment reported in diabetic patients is dependent on abnormalities in physiological bone growth and corresponds to abnormalities of the growth hormone -insulin-like growth-I (GH -IGF-I) axis. These alterations seem to be related to appropriate insulin levels and thereby to glycaemic control as judged by haemoglobin levels. Modern diabetes care, particularly intensified insulin regimens, might improve metabolic control in patients with T1DM, therefore preventing abnormalities of the GH -IGF-I axis and leading to normal growth and final height similar to that of their unaffected peers. European Journal of Endocrinology 151 U109-U117

This review focuses on the current knowledge of the effects of thyroid hormones on central nervous system differentiation and development in animals and the human fetal brain. The outcomes of children with congenital hypothyroidism and of newborns with hypothyroid pregnant mothers are emphasized, focusing on how therapies could affect and especially improve the outcomes.

Neck pain is a prevalent health problem, largely reported in adult patients. However, very recent data show that new technologies are inducing a shift in the prevalence of this relevant issue from adulthood to all of the pediatric ages. In fact, the precocious and inappropriate use of personal computers and especially cell phones might be related to the development of a complex cluster of clinical symptoms commonly defined as “text neck syndrome”. The purpose of this article is to analyze the new phenomenon of the “text neck syndrome”, the underlying causes and risk factors of musculoskeletal pain, that can be modified by changes in routine life, in different cultures and habits, and on the “text neck syndrome” as increased stresses on the cervical spine, that can lead to cervical degeneration along with other developmental, medical, psychological, and social complications. Findings support the contention that an appropriate approach for an early diagnosis and treatment is crucial to properly evaluate this emerging issue worldwide in children and adolescents who spend a lot of time watching smartphones and computers; additional research with more rigorous study designs and objective measures of musculoskeletal pain are needed to confirm significant relationships. Existing evidence is limited by non-objective measures and the subjective nature of musculoskeletal pain.

α-Hydroxybutyrate and BCAA concentrations during an OGTT characterize insulin-resistant youth and predict worsening of glycemic control. These findings provide potential biomarkers for risk assessment of type 2 diabetes and new insights into IR pathogenesis.

Obesity has been estimated to decrease life expectancy by as little as 0.8 to as much as 7 years being the second leading cause of preventable death in the United States after smoking. Along with the increase in the prevalence of obesity, there has been a dramatic rise of the prevalence of prediabetes and type 2 diabetes among adolescents. Despite that, very little is known about the pathogenesis of these conditions in pediatrics and about how we could detect prediabetes in an early stage in order to prevent full blown diabetes. In this review we summarize the current knowledge on the pathophysiology of prediabetes and type 2 diabetes in adolescents and describe how biomarkers of beta-cell function might help identifying those individuals who are prone to progress from normal glucose tolerance towards prediabetes and overt type 2 diabetes. To better understand and fight this disease, we will need to explore and develop novel therapeutic strategies and individuate more sensitive and specific biomarkers that can allow an earlier detection of the disease.

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