Background T2D (Type 2 Diabetes) 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 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.

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.

Atherosclerotic cardiovascular disease (ASCVD) represents the major cause of morbidity and mortality worldwide. The onset of the atherosclerosis process occurs during childhood and adolescence, subsequently leading to the onset of cardiovascular disease as young adults. Several cardiovascular risk factors can be identified in children and adolescents; however, hyperlipidemia, in conjunction with the global obesity epidemic, has emerged as the most prevalent, playing a key role in the development of ASCVD. Therefore, screening for hyperlipidemia is strongly recommended to detect high-risk children presenting with these disorders, as these patients deserve more intensive investigation and intervention. Treatment should be initiated as early as possible in order to reduce the risk of future ASCVD. In this review, we will discuss lipid metabolism and hyperlipidemia, focusing on correlations with cardiovascular risk and screening and therapeutic management to reduce or almost completely avoid the development of ASCVD.

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.

Background: Lipodystrophy includes a wide group of diseases characterized by reduction, absence or altered distribution of adipose tissue. Lipodystrophies are classified into generalized or partial, according to the fat distribution, and congenital or acquired, considering the aetiology. Summary: Impaired glucose and lipid metabolism is typically present, thus severe insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis are frequent complications. Because of the rarity and the diversification of lipodystrophies, diagnosis might be challenging, typically for partial forms that cannot be easily recognized, leading to progression of the several metabolic abnormalities associated. First management of lipodystrophy is diet and lifestyle changes, followed by the treatment of metabolic complications. Replacement therapy with metreleptin, currently available in the United States and Europe, has shown improvement of metabolic profile in a great number of patients with lipodystrophy. Key messages: The purpose of this review is to describe the phenotypic characteristics of all the known lypodistrophic types and to present specific steps for obtaining early diagnosis and assessing the best treatment of lipodystrophy.