Valentina Chiavaroli

GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome

OBJECTIVEnGNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty.nnnDESIGNnLongitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height.nnnMETHODSnTwenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed.nnnRESULTSnIn GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (P=0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (P=0.03 for both) as well as higher DHEAS and androstenedione levels (P=0.02 and P=0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively, P=0.04; 56 and 23.6% respectively, P=0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (P=0.03).nnnCONCLUSIONSnIn girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence.

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.

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

BACKGROUND AND AIMSnThe 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.nnnMETHODS AND RESULTSnWe 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).nnnCONCLUSIONnThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.

One-hour post-load plasma glucose levels associated with decreased insulin sensitivity and secretion and early makers of cardiometabolic risk

PurposeObese adults with normal glucose tolerance (NGT) but with 1-hour post-load plasma glucose (1hPG)u2009≥u2009155xa0mg/dl are at higher risk of developing type 2 diabetes (T2D) and cardiometabolic complications. Little information is available for the pediatric population, where recently, a lower cutoff, 132.5xa0mg/dl, has been suggested as being more sensitive to identify subjects at risk of T2D. Our aim was to assess whether obese Caucasian youth with 1hPGu2009≥u2009132.5xa0mg/dl have worse insulin sensitivity and secretion and a worse cardiometabolic profile compared to obese youth with 1hPGu2009<u2009132.5xa0mg/dl.MethodsMedical records of 244 (43% male; age: 11.1u2009±u20092.7years) overweight/obese children and adolescents, who had undergone an oral glucose tolerance test (OGTT), were retrieved. Anthropometric and biochemical data were collected from the hard copy archive. Indexes of insulin resistance (HOMA-IR), insulin sensitivity (WBISI), and insulin secretion (Insulinogenic Index, Disposition Index) were calculated.ResultsOf the 244 records analyzed, 215 fulfilled criteria for NGT and had complete biochemical data. Among NGT patients, 42 (19.5%) showed 1hPGu2009≥u2009132.5xa0mg/dL (high-NGT), while the remaining had 1hPGu2009<u2009132.5xa0mg/dL (low-NGT). The high-NGT group showed a higher male prevalence (59.5 vs 37%), lower Disposition Index (0.54 [0.39–0.71] vs 0.79 [0.47–1.43]), and WBISI (0.24 [0.18–0.35] vs 0.33 [0.23–0.50]) than the low-NGT group. High-NGT subjects also showed a trend towards lower HDL-cholesterol and higher triglycerides/HDL-cholesterol ratio (2.13 [1.49–3.41] vs 1.66 [1.24–2.49]).ConclusionsIn overweight/obese NGT Caucasian youth a 1hPGu2009≥u2009132.5xa0mg/dL was able to identify those with impaired insulin sensitivity and secretion and a trend towards a worse cardio-metabolic profile, a group likely at risk for future T2D.

Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine.

Background and proposeHypertension is the most important cardiovascular complication of obesity, even during childhood. Several studies have demonstrated that there is a natural progression of hypertension from childhood to adulthood. However, there are no data reporting a potential worsening in blood pressure (BP) already moving from the pre-pubertal to the pubertal period in obese youths. The aim of this study was to evaluate early change in BP and its relation to insulin resistance (IR) and asymmetric dimethylarginine (ADMA).MethodsThirty obese children underwent a first assessment when they were pre-pubertal (visit_1) and were re-evaluated after a mean of 4.5xa0years (visit_2). At both visits, anthropometric parameters were assessed, blood samples were collected for measurement of insulin, glucose and ADMA and a 24-h ambulatory BP monitoring was performed.ResultsAt visit_2, the study participants presented increased HOMA-IR and ADMA compared to visit_1 (HOMA-IR: 3.6xa0±xa02.8 vs 2.8xa0±xa01.4, pxa0=xa00.01; ADMA: 1.57xa0±xa00.78 vs 0.77xa0±xa00.52xa0μmol/l, pxa0<xa00.001). Values of 24-h systolic and diastolic BP SDS (0.86xa0±xa00.79 vs 0.42xa0±xa00.83, pxa0=xa00.001; −0.45xa0±xa00.82 vs 0.08xa0±xa00.51, pxa0=xa00.001) were significantly increased at visit_2 compared to visit_1. At both visits, BMI-SDS, HOMA-IR and ADMA were associated with 24-h BP. In addition, over-time changes in IR and ADMA influenced changes in systolic blood pressure and diastolic blood pressure from childhood to adolescence (pxa0<xa00.05).ConclusionsChanges in BP already occur moving from the pre-pubertal to the pubertal period in obese children, and modifications in insulin resistance and ADMA seem to be implicated in this early progression in BP.

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

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.