Angelika Mohn

Macrovascular angiopathy in children and adolescents with type 1 diabetes.

Diabetes represents one of the most common diseases globally. Worryingly, the worldwide incidence of type 1 diabetes (T1D) is rising by 3% per year. Despite the rapid increase in diabetes incidence, recent advances in diabetes treatment have been successful in decreasing morbidity and mortality from diabetes‐related retinopathy, nephropathy, and neuropathy. In contrast, there is clear evidence for the lack of improvement in mortality for cardiovascular diseases (CVDs). This emphasizes the importance of focusing childhood diabetes care strategies for the prevention of CVD in adulthood. Furthermore, although most work on diabetes and macrovascular disease relates to type 2 diabetes, it has been shown that the age‐adjusted relative risk of CVD in T1D far exceeds that in type 2 diabetes. As T1D appears predominantly during childhood, those with T1D are at greater risk for coronary events early in life and require lifelong medical attention. Because of the important health effects of CVDs in children and adolescents with T1D, patients, family members, and care providers should understand the interaction of T1D and cardiovascular risk. In addition, optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional cardiovascular risk factors to optimize those well‐recognized as well as new specific risk factors which are becoming available. Therefore, a complete characterization of the molecular mechanisms involved in the development and progression of macrovascular angiopathy is needed. Furthermore, as vascular abnormalities begin as early as in childhood, potentially modifiable risk factors should be identified at an early stage of vascular disease development. Copyright

Improved oxidative stress and cardio-metabolic status in obese prepubertal children with liver steatosis treated with lifestyle combined with Vitamin E.

Abstract In obese adults with non alcoholic fatty liver disease (NAFLD), treatment with Vitamin E has resulted in an improvement in liver histology, whereas variable and limited results are available in children. Our aim was to assess whether lifestyle combined with supplementation with Vitamin E might reduce oxidative stress and improve cardio-metabolic status in obese children with NAFLD. 24 obese prepubertal children (16M) followed a 6-month lifestyle intervention combined with Vitamin E supplementation (600 mg/day) and they were compared with 21 age and sex-matched obese peers who underwent lifestyle intervention only. At baseline and after 6-month urinary prostaglandin F2α (PGF-2α), endogenous secretory receptor for advanced glycation end products (esRAGE), high sensitivity C-reactive protein (hs-CRP), alanine aminotransferases (ALT), lipid profile, glucose, and insulin were assessed. The two groups were comparable for age (8.3 ± 1.6 vs 8.4 ± 1.3 yr), sex and BMI SDS (2.16 ± 0.29 vs 2.13 ± 0.28). At the beginning of the study, PGF2-α, esRAGE hsCRP, ALT, lipid profile and HOMA-IR levels were similar between the two groups (all p > 0.05). After 6-month treatment, levels of PGF2-α (p < 0.001) significantly decreased and esRAGE significantly increased (p < 0.001) in children treated with Vitamin E. A significant reduction was also found in ALT (p = 0.001), lipid profile and HOMA-IR (p < 0.001). In contrast, no significant change in any of these markers was detected in the lifestyle only group. In conclusion, Vitamin E supplementation was associated with a significant reduction in oxidative stress and improved cardio-metabolic alterations. These data suggest that Vitamin E supplementation could represent a valuable treatment in obese children affected by NAFLD.

An insulin-like growth factor-I receptor defect associated with short stature and impaired carbohydrate homeostasis in an Italian pedigree.

Background: 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.

Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

BACKGROUND AND AIMS The Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima-media thickness (cIMT) in pre-pubertal hypercholesterolaemic children. METHODS AND RESULTS We performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05). CONCLUSION The Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

Primary and Secondary Amenorrhea

Puberty represents a particular period of life characterized by hormonal changes and physical and psychological modifications leading children from childhood to adolescence. During this period, menarche represents the most important event in females. Age of menarche is different among populations and has been recognized as an useful marker of socio-economic status, as well as dietary and environmental patterns (Chumlea et al., 2003; Swenson & Havens, 1987; Thomas et al., 2001). Generally, the first menstrual cycle takes place between 12 and 13 years of age, with 98% of girls having menarche by 15 years of age (Diaz, 2006). The normal range for menstrual cycles is between 21 and 45 days, with flow length varying from 2 to 7 days (Flug et al., 1984; World Health Organization Task Force on Adolescent Reproductive Health, 1986). During the first 2 years after menarche, menses length is often abnormal due to immaturity of the hypothalamic-pituitary-ovarian axis (Diaz, 2006); however, cycles range can be regular also in the first gynecologic year (Flug et al., 1984; World Health Organization Task Force on Adolescent Reproductive Health, 1986). Amenorrhea is defined as the complete absence or anomalous cessation of menstrual cycles in females during reproductive years. Just in three situations amenorrhea is considered physiological: during pregnancy, lactation and menopause. In all other situations, amenorrhea can be due to many pathological conditions and merits a careful assessment. Amenorrhea is classified as primary and secondary according to its occurrence before or after menarche, respectively (The Practice Committee of American Society for Reproductive Medicine, 2008). Amenorrhea is defined primary when menarche does not occur by the age of 16 years in a girl with complete secondary sexual development, or by the age of 14 years in a girl without secondary sexual development. Amenorrhea is defined secondary when menstrual cycles disappear for 6 consecutive months in a girl with irregular menses or for 3 consecutive months in a girl with regular menses (Deligeoroglou et al., 2010). According to the American Society for Reproductive Medicine, currently in literature many causes of amenorrhea have been recognized (The Practice Committee of American Society for Reproductive Medicine, 2008), including: • anatomic defects of the genital tract • hypothalamic/pituitary causes • ovary insufficiency • endocrinopathies • chronic oligoor anovulation

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes

To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule‐1 (ICAM‐1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function.

Corticosteroids in Pediatric Endocrinology

Glucocorticoids are human steroid hormones secreted by the adrenal cortex that play a critical role in several biologic processes. At “pharmacologic” or “stress-related” doses, glucocorticoids are irreplaceable therapeutic means for many allergic, inflammatory, autoimmune, and lymphoproliferative diseases. Glucocorticoids also remain the cornerstone of treatment for certain life-threatening endocrinopathies in childhood, such as congenital adrenal hyperplasia, Addison disease, and steroid replacement therapy for subjects with secondary hypothalamic–pituitary–adrenal axis deficit. In this chapter the physiology of the hypothalamic–pituitary–adrenal axis and of glucocorticoids is described. In addition, the therapeutic approach to glucocorticoid replacement therapy in the most relevant endocrinopathies in childhood (i.e., congenital adrenal hyperplasia, Addison disease, and Cushing disease) is elucidated.

Growth, Puberty, and Nutritional Disturbances

Oxidative stress can be defined as an imbalance between oxidant and antioxidant status, which occurs in physiological conditions. Of note, the alteration of the oxidant–antioxidant system may also influence the pathogenesis of many diseases. Recent data have clearly shown that oxidative stress plays an important role in the onset and progression of several pathologies even during childhood. The aim of this chapter is to summarize the most important and recent findings regarding the role of oxidative stress in growth, puberty, and nutrition. A careful analysis and critical interpretation of the literature data have been made in order to establish the correlation between the special needs of childhood and the impairment of oxidant–antioxidant system. Emerging evidences suggest that children affected by growth, puberty, as well as nutritional disturbances are highly exposed to oxidative stress. New clinical studies need to be performed to establish possible prophylactic actions or treatment protocols limiting the oxidative damage in childhood.