Early Insulin Resistance, Type 2 Diabetes, and Treatment Options in Childhood

Background: Type 2 diabetes (T2D) 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 insulin resistance (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

An Insulin-Like Growth Factor-I Receptor Defect Associated with Short Stature and Impaired Carbohydrate Homeostasis in an Italian Pedigree

Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. Methods: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R mutation (p.Tyr387X): an 18-year-old male (index case), his sister and two paternal aunts. Results: All family members showed a variable degree of impairment in prenatal growth, with birth weight standard deviation scores (SDS) between –1.65 and –2.37 and birth length SDS between –1.78 and –3.08. Their postnatal growth was also impaired, with height SDS between –1.75 and –4.86. The index case presented high IGF-I levels during childhood and adolescence and delayed bone age. The index case and his two paternal aunts had impaired glucose tolerance (IGT) associated with a variable degree of alterations in insulin sensitivity and secretion. In contrast, the index case’s sister, who had had IGT during pregnancy, showed normal glucose metabolism but reduced insulin sensitivity. Conclusion: This is the first study showing an association between a novel IGF1R mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism

Increased GLP-1 response to oral glucose in pre-pubertal obese children.

BACKGROUND: Gastrointestinal hormones, such as glucagon-like peptide (GLP-1), have been hypothesized to play a role in the pathogenesis of obesity-related complications. However, few data are available in youth. The objective of this study was to investigate the GLP-1 response to oral glucose load in obese pre-pubertal children and its relationship with insulin secretion. METHODS: Ten pre-pubertal obese children [five boys; 10.5±1.6 years; body mass index-standard deviation score (BMI-SDS): 2.2±0.5] and 10 controls (eight boys; 9.9±1.2 years; BMI-SDS: -0.7±0.5) underwent a modified oral glucose tolerance test (OGTT) to evaluate post-load glucose, insulin and GLP-1 responses. Insulin sensitivity [homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and secretion [HOMA-beta, insulinogenic index (IGI)] indexes, area under the curve (AUC) for glucose, insulin and GLP-1 were calculated. RESULTS: In obese children GLP-1 AUC values were higher and correlated with BMI-SDS (r=0.45; p=0.04), HOMA-IR (r=0.53; p=0.01) and fasting glucose (r=0.68; p=0.001). CONCLUSIONS: Obese children showed an increased GLP-1 response to oral glucose. These changes might likely represent a compensatory mechanism to avoid post-prandial hyperglycemia and allow a normal glucose tolerance

Etanercept Improves Lipid Profile and Oxidative Stress Measures in Patients with Juvenile Idiopathic Arthritis

Objective.To investigate the effect of 1-year treatment with the anti-tumor necrosis factor-α (TNF-α) drug etanercept on lipid profile and oxidative stress in children and adolescents with juvenile idiopathic arthritis (JIA).Methods.Thirty children with JIA (22 females; mean age 12.3 ± SD 5.7 yrs), all eligible for anti-TNF-α treatment, were assessed at baseline and after 6- and 12-month treatment with etanercept. Disease activity was determined using the Juvenile Arthritis Disease Activity Score (JADAS). Blood samples were drawn to measure the acute-phase reactants C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), lipids, and the proinflammatory cytokines TNF-α, interleukin-1β (IL-1β), IL-6 and interferon-γ. To measure the oxidative stress marker 8-iso-prostaglandin F2α, 24-h urine samples were collected.Results.Inflammatory indicators (CRP and ESR) and JADAS scores improved significantly after 1 year of etanercept treatment (all p < 0.001). Proinflammatory cytokines showed significant reduction during the study period (all p < 0.001). Similar reductions were detected in total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p = 0.04), and triglycerides (p < 0.001), whereas no significant change was found in high-density lipoprotein cholesterol. No side effects were observed during the treatment period.Conclusion.This study shows for the first time that anti-TNF-α therapy for JIA is associated not only with a beneficial effect on clinical disease activity and inflammatory indexes, but also with improved lipid profile and oxidative stress. These findings suggest that TNF-α blockers might reduce atherosclerotic risk in children with JIA

A school educational intervention based on a serious game to promote a healthy lifestyle

Background: Maintaining a healthy lifestyle is a basic aspect of well-being. Since public health surveillance systems underlie high prevalence of obesity and diet-related ill health, efforts to provide effective intervention to prevent these conditions are of primary importance. The present study aims to test and validate a school intervention based on a serious game (SG) directed to empower a healthy lifestyle in children, actively involving their parents and teachers. Methods: A quantitative, pre/post-test study design assessed effects of a healthy lifestyle intervention on healthy food knowledge, food consumption frequency and level of interest. Participants were 79 children attending primary school and lower secondary school in the Chieti-Pescara urban and rural areas of Italy. Measures were collected during two supervised steps of assessment (T1 and T2). Results: Sixty-seven children completed the intervention. After playing the SG, participants reported higher levels of knowledge on healthy diet. Children also showed significant improvement in healthy eating habits. Moreover, high rates of endorsement about fun, playability, learning perception and goodness of characteristics emerged. Conclusion: This study, targeted children, but directly involving families, shows the effectiveness of a school educational intervention based on a SG, an innovative tool with potential benefits for preventive purposes, despite the short term of intervention.  Issues related to the implementation of a method for prevention tailored for children are discussed

Asymmetric Dimethylarginine in Obese Youth: Relationship with 24-hour Ambulatory Blood Pressure

The incidence of amputation worldwide is 1.5 per 1000 habitants and the total number of amputees is about 10 million..

Technology-based intervention for healthy lifestyle promotion in Italian adolescence.

Introduction. Healthy lifestyle promotion programs are essential to prevent metabolic diseases such as obesity and diabetes. Adolescents could represent the ideal target population especially using serious web games. Objective. To test the improvement of knowledge about healthy nutrition in adolescents and to analyze participants’ enjoyment in playing the web game “Gustavo in Gnam’s Planet” in comparison with a leisure web game. Subjects and Methods. Sixty-five adolescents were engaged in three supervised group sessions. Measures about healthy food knowledge and games’ enjoyment were collected during the three stages of assessment. Results. After playing Gustavo in Gnam’s Planet, participants significantly improved their knowledge on a healthy diet, compared to the recreational web games; whereas the level of fun experienced while playing the recreational and the educational games was not significantly different. Conclusions. Gustavo in Gnam’s Planet is an important promising tool, with entertainment property, to promote a healthy lifestyle in Italian adolescents.