Not only for caregivers: intranasal glucagon for severe hypoglycaemia in a simulation study.

AIMS: To evaluate: (i) the propensity of paediatrics and emergency medicine residents to select different therapeutic options and (ii) the speed and administration success in a high-fidelity simulation of severe hypoglycaemia in a child with type 1 diabetes (T1DM). METHODS: In this single-centre high-fidelity simulation study, 51 paediatrics or emergency medicine residents were exposed to a scenario of severe hypoglycaemia in a T1DM child attending an ambulatory setting, before and after a training on the preparation and administration of both injectable and IN glucagon. Time for drug delivery and its effectiveness were collected. RESULTS: Before training, 45.1% of participants chose to administer injectable glucagon, 43.1% intravenous glucose solution, 5.9% intranasal (IN) glucagon, and 5.9% took no action. Administration was successful in 74% of injectable glucagon, 33.3% intravenous glucose solution, and 22.7% IN glucagon. After training, 58.8% of participants chose IN and 41.2% injectable glucagon, with 100% of successful administrations for IN glucagon and 90.5% for injectable glucagon. Time to successful administration was shorter for IN than injectable glucagon (23 ± 10 vs. 38 ± 7 s, p < 0.0001). CONCLUSIONS: IN glucagon is an easy and effective option for severe hypoglycaemia treatment, with an almost zero possibility of failure provided that adequate training is imparted.

Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes.

OBJECTIVE: Two cases of Type 1 Diabetes (T1D) in pediatric subjects treated with supplementation with high dose vitamin D and omega 3 are reported. A similar pattern of remission of the disease was observed, resulting in restoration and subsequent persistence of optimal metabolic control, one and two years after T1D onset. Minimal basal insulin administration (0.1 IU/kg/die) in a single evening injection was required. The immunomodulatory and anti-inflammatory properties of the supplements were likely contributing to the observed effect. Similarities in genotyping and autoantibody patterns in these two cases could be of assistance to identify which subjects with T1D could benefit from this supplemental therapy. High dose vitamin D and omega 3 could be of assistance in childhood T1D therapy, to prolong preservation of endogenous insulin secretion in the absence of side effects. We do not know how long the state of remission can last, but these initial results are promising and represented a significant benefit for the two pediatric subjects treated. Larger controlled studies will determine the long-term effect of this proposed supplementation and its possible cost-benefits, including reduction of hypoglycemic episodes and complications.

Can Type 1 diabetes progression be halted? Possible role of high dose vitamin D and omega 3 fatty acids.

In Type 1 Diabetes (T1D) in children, close to the onset the requirements of insulin are often reduced. This represents a transient recovery of endogenous insulin secretion named "honeymoon" because transient and followed by a progressive decline in C-peptide secretion. This case report describes the effect of administration of high dose vitamin D and Ω-3 fatty acids on T1D progression in a 8-year-old child. At today after one year and a half from the onset of T1D, the subject shows a near-normal blood glucose with the administration of 1.5-2 UI of insulin once a day. Thus this report may be of assistance to design additional studies to determine and validate the effect of administration of vitamin D and Ω-3 fatty acids on the progression of T1D.

Vitamin D status and type 1 diabetes in children: evaluation according to latitude and skin color.

AIM: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin color. METHODS: We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison. RESULTS: Caucasian (21.4±1.5 vs. 24.0±0.5 ng/mL, P<0.05) and Moroccan children with T1D (12.0±2.6 vs. 17.1±1.7 ng/mL, P<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.

Comparison of two classifications of metabolic syndrome in the pediatric population and the impact of cholesterol.

BACKGROUND: To establish the rate of agreement in predicting metabolic syndrome (MS) in different pediatric classifications using percentiles or fixed cut-offs, as well as exploring the influence of cholesterol. SUBJECTS AND METHODS: Cross-sectional study in a tertiary care center. Nine hundred and twenty-three obese children and adolescents were evaluated for metabolic characteristics, cholesterol levels, the agreement rate and prevalence of MS across age subgroups with pediatric National Cholesterol Education Program/ Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) classifications. RESULTS: The overall prevalence of MS was 36.2% and 56.7% with NCEPATP III and IDF. The overall concordance was fair (k: 0.269), with substantial values observed only in children older than 10 (k: 0.708) and 16 yr (0.694). Concordant subjects for both classifications, ≤6 yr, had higher triglycerides, blood pressure (p<0.05) and lower HDL-cholesterol (p<0.0001), with respect to those found to be discordant. Concordant subjects ranging 6-10 yr had all parameters higher than those discordant for IDF (p<0.01) and insulin resistance (p<0.05) than those discordant for NCEP-ATP III. Concordant subjects ≥10 yr presented more altered parameters than those included only in NCEP-ATP III (p<0.05). Overt glucose alterations were uncommon (7.4%; confidence interval 95% 0.1-14.9%), although glucose was modestly higher in MS subjects (p<0.01). Total and LDL-cholesterol was lower in subjects with MS than in those without (p<0.05), and in concordant rather than discordant subjects (p<0.05). CONCLUSIONS: Classifications of MS do not identify the same pediatric population. Subjects who satisfied any classification were the most compromised. Lipid alterations were precocious in the youngest. Obese youths with MS presented lower total and LDL-cholesterol.

Acylated and unacylated ghrelin levels in normal weight and obese children: influence of puberty and relationship with insulin, leptin and adiponectin levels.

BACKGROUND: Ghrelin circulates in blood as acylated (AG) and unacylated (UAG) ghrelin. The physiological role of the two forms is poorly understood, in particular in childhood. Aim of the study was to evaluate the AG and UAG levels in obese and normal weight (NW) children, pre-pubertal and pubertal, and their relationship with insulin, leptin and adiponectin levels. SUBJECTS AND METHODS: A population based study in which AG, UAG, leptin, adiponectin, glucose, insulin, testosterone or estradiol levels, insulinemic indexes were evaluated in 82 NW and 58 obese (OB) children. RESULTS: Both ghrelin forms in NW were higher (AG, p<0.02; UAG, p<0.0001) than in OB subjects, with similar ratio AG/UAG . While no differences were observed for gender, puberty AG (p<0.01) and UAG (p<0.0001) levels were higher in pre-pubertal than pubertal NW and OB subjects. Adiponectin levels in NW subjects were higher (p<0.001), while leptin and insulin levels were lower (p<0.0001) than in OB subjects. NW children showed homeostasis model assessment (HOMA) and HOMAß indices lower than OB children (p<0.0001) with a higher a quantitative insulin sensitivity check index (p<0.0001). AG and UAG levels correlated to each other (p<0.0001), each showing a negative correlation to age, height, weight and body mass index. Both forms, but more strongly UAG, correlated with adiponectin, leptin, and insulin. CONCLUSIONS: OB children show lower levels of both AG and UAG when compared to NW subjects, with lower levels during puberty. These results demonstrate a peculiar strong relationship between UAG levels and metabolic parameters in the pediatric population, suggesting a role for UAG in metabolic functions.

Acylated/unacylated ghrelin ratio in cord blood: correlation with anthropometric and metabolic parameters and pediatric lifespan comparison.

CONTEXT: Ghrelin is a peptide with multiple functions that circulates in acylated (AG) and unacylated (UAG) forms. However, the role of ghrelin in neonates (NN) remains to be clarified. OBJECTIVE: The aim of this study was to determine ghrelin concentrations of the two forms in NN to clarify their biological roles. As such, ghrelin levels at birth were compared with those in later life. SETTING AND DESIGN: Tertiary Care Center. In this cross-sectional study, we evaluated AG, UAG, AG/UAG ratio, and insulin levels in venous cord blood from NN and in fasted normal weight (NW) and obese (OB) children, both prepubertal and pubertal. SUBJECTS: We studied 82 NN, 82 NW, and 58 OB children. RESULTS: AG levels were lower in NN than in NW and OB children (P<0.0001), more specifically the prepubertal NW and OB children (P<0.0001). UAG levels were higher in NN than in NW and OB children (P<0.0001). Therefore, the AG/UAG ratio was lower in NN than in NW and OB children (P<0.0001). NN showed insulin levels similar to NW and lower than OB children (P<0.0001). At birth UAG was positively correlated with AG (Pearson: 0.425; P<0.0001) and negatively with insulin (-0.253; P<0.02). In NW and OB, UAG and AG were positively correlated to each other and negatively correlated with insulin and body mass index (-0.566; P<0.0001). CONCLUSIONS: NN compared with children, showed higher UAG and lower AG levels. The AG/UAG ratio showed a very different profile in NN, being lower than in NW and OB children, thus suggesting a different metabolic function for the two forms in NN. Further studies are needed to clarify the exact role of the different ghrelin forms in NN.

Etiopathogenetic advances and management of holoprosencephaly: from bench to bedside.

Holoprosencephaly (HPE) is a complex brain malformation caused by impaired or incomplete midline division of the prosencephalon. It's characterized by cerebral and facial anomalies of different levels of severity. Both genetic and environmental factors are known to cause HPE, but they cover only few cases. Genetic causes are responsible for about 20% of cases: they are chromosomal abnormalities and gene mutations: up to date, nine genes (SHH, ZIC2, SIX3, TGIF, PATCHED1, TDGF1/CRIPTO, FAST1, GLI2 and DHCR) are definitely associated with HPE, but many others candidate gene are under investigation. The diagnosis of HPE is usually prenatal and is based on systematic ultrasound scan (US) and magnetic resonance imaging (MRI). Children with HPE have many medical problems in agreement with the severity of the brain malformation: craniofacial abnormalities, neurological signs, endocrine disorders, oromotor and dysautonomic dysfunction, thus requiring a multidisciplinary team for symptomatic treatment of manifestations, prevention of complications and parental support. Genetic counselling is an important step, often made difficult by extreme phenotypic variability, genetic heterogeneity, and a high risk of recurrence in apparently sporadic cases. In conclusion it can be concluded that we are far from a complete explanation of the etiopathogenesis. Future researches on genomic rearrangements all over the genome with techniques like the CGH array should lead to the identification of other causal genes and could improve diagnosis and prognosis. A skill multidisciplinary approach is mandatory to offer the better clinical assistance to patients and their parents.

[Germinoma: a rare cerebral tumor causing central diabetes insipidus in childhood]. / Il germinoma: un raro tumore cerebrale causa di diabete insipido centrale in età infantile.

Germinoma represents 7.8% of cerebral tumors in pediatric age and 50-65% of germ cell cerebral tumors. Generally it is a definite lesion of the pineal gland or suprasellar region, frequently occurring in the first three decades of life. Clinical presentation depends on tumor localization. Pineal lesions generally determine symptoms due to the compression of cerebral structures, causing Parinaud syndrome, while hypothalamic lesions are often characterized by diabetes insipidus, hypopituitarism and visual defects. In the absence of these classic signs and symptoms, however, the diagnosis of germinoma can be difficult. We presented the case of an 8-year-old boy, referred to our clinic for polyuria and polydipsia. Hormonal evaluations demonstrated central diabetes insipidus (CDI), with normal anterior pituitary function. Magnetic resonance imaging (MRI) showed a lack of posterior pituitary gland and partial pituitary stalk enlargement. The patient started therapy with desmopressin (Minirin) with good hydro-electrolytic balance. During follow-up the pituitary function became insufficient with low growth velocity. A second MRI demonstrated a bifocal lesion with dyshomogeneous and cystic appearance, suggesting the diagnosis of germinoma. On the basis of this case report we would like to point out the importance of an early diagnosis in order to improve the prognosis of the disease and the necessity of a careful follow-up of these patients.

Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake.

CONTEXT: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. OBJECTIVE: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. METHODS: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. RESULTS: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. CONCLUSIONS: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.

Role of ghrelin in the regulation of appetite in children.

Ghrelin, the new recently discovered hormone, is a 28 amino-acid acylated peptide predominantly produced by the stomach characterized by a strong GH-releasing activity mediated by the hypothalamic-pituitary GH secretagogues (GHSs) receptors. Ghrelin and GHSs, acting on central and peripheral receptors, exert other actions such as stimulation of ACTH and prolactin secretion, influence on insulin secretion and glucose metabolism, orexigenic effect and modulatory activity on the neuroendocrine and metabolic response to starvation, influence on exocrine gastro-entero-pancreatic functions, cardiovascular activities and modulation of cell proliferation and apoptosis. The wide spectrum of ghrelin action requires further studies to provide critical information on the role of ghrelin and the potential perspectives of its analogues in the clinical practice. This point is of particular interest in the field of pediatric endocrinology and metabolism because the ghrelin story started focusing on GH deficiency and is now extending to aspects that once again are of major relevance such as obesity and eating disorders, regulation of the hypothalamus-pituitary-adrenal and gonadal axis. More studies are needed to evaluate the real impact of ghrelin in different non endocrine processes and the possible use of ghrelin analogues in different diseases condition.