[New Insulins for Type 1 Diabetes treatment]. / Nuevas Insulinas en el tratamiento de la Diabetes Tipo 1.

Insulin therapy is complex in pediatric patients because they present greater variations in insulin requirements. Traditional insulins have limitations related to time of onset of action and duration of effect, which has led to the development of new insulins, seeking to reduce chronic complications, severe or nocturnal hypoglycemia, and to improve adherence to therapy. This review updates the information on new insulins, their mechanisms of action and the benefits they provide in the treatment of diabetes. Insulin analogues attempt to mimic the physiological secretion of the hormone, including time of action and duration of effect. The most used prandial analogs are the so-called rapid-acting insulins, including Faster Aspartic and the new basal insulins, glargine U300 and degludec, which have a prolonged action of more than 24 hours and therefore require a daily dose. New technologies under development include biosimilar insulins such as the glargine biosimilar, already available in the clinic. New formulations are being developed for the future, as well as novel ways of dispersing them, mimicking the action of pancreatic cells, which will allow a more physiological and personalized management of the disease.

Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children.

OBJECTIVES: The objective of this study was to compare the diurnal variations in cortisol and cortisone concentrations in serum and saliva among extremely preterm (EPT), very preterm (VPT), and full-term (FT) children, all born appropriate for gestational age (AGA). METHODS: EPT, VPT, and FT children, all born AGA, were recruited from two healthcare centers. Cortisol and cortisone concentrations in serum and saliva were measured by liquid chromatography-mass spectrometry (LC‒MS). Statistical analysis was performed using nonparametric tests. RESULTS: A total of 101 children (5.0-8.9 years old) were included in this study: EPT=18, VPT=43 and FT=40. All groups had similar distributions in terms of age, birth weight standard deviation score (SDS) and BMI (SDS), showing no differences in serum ACTH, cortisol, or cortisone levels. Additionally, salivary cortisol and cortisone concentrations decreased significantly throughout the day (p-values<0.0001). Salivary cortisol concentrations were below the limit of detection (0.55 nmol/L) before dinner and before bedtime in approximately one-third and two-thirds of all children, respectively. Salivary cortisone was detectable in all but one sample. CONCLUSIONS: The diurnal cortisol rhythm was preserved in all preterm children, regardless of their gestational age, and no differences in cortisol concentrations among the groups were found. This may have significant implications for the clinical management and follow-up of preterm individuals.

Variación estacional de 25-hidroxi-vitamina D3, hormona paratiroidea y fosfatasa alcalina en niños escolares / Seasonal variations in 25-hydroxy vitamin D3, parathormone and alkaline phosphatase in school-aged children

INTRODUCCIÓN: El principal rol de la vitamina D es la regulación del metabolismo del calcio, cuya principal fuen te es la vitamina D3 que se obtiene principalmente por la acción de la luz ultravioleta (UV) en la piel. OBJETIVO: Evaluar las diferencias estacionales en las concentraciones de 25-hidroxi-vitamina D3 (25OHVitD3), hormona paratiroidea (PTH), fosfatasa alcalina (FA) y calcio en niños en edad esco lar. SUJETOS Y MÉTODO: Se midieron las concentraciones de 25OHVitD3, PTH, FA y calcio en niños de 5 a 8 años, sin suplementación de Vitamina D, reclutados en Santiago de Chile (latitud -33.4372) en distintas estaciones del año. El estatus de VitD fue definido como suficiente con concentraciones de 25OHVitD3 > 20 ng/mL (50 nmol/L), insuficiente 12-20 ng/mL (30-50 nmol/L) y deficiente 20 ng/mL) en verano, lo que disminuyó significativamente en invierno (54,3%, p < 0,0001). CONCLUSIONES: Las concentraciones de 25OHVitD3 disminuyeron en aproximadamente la mitad de los niños durante el invierno, lo que se vio acompañado de un aumento de la PTH y FA, asociado a concentraciones normales de calcio. De acuerdo a nuestros resultados, la suplementación con VitD en niños podría ser necesaria durante otoño e invierno.

INTRODUCTION: The main role of Vitamin D is to regulate calcium metabolism, whose main source is vitamin D3 ob tained mostly from the action of ultraviolet (UV) light on the skin. OBJECTIVE: To evaluate the seaso nal differences in the concentrations of 25-hydroxy-vitamin D3 (25OHVitD3), parathyroid hormone (PTH), alkaline phosphatase (ALP), and calcium in school-age children. SUBJECTS AND METHOD: The concentrations of 25OHVitD3, PTH, ALP, and calcium were measured in children from Santiago, Chile (latitude -33.4372), aged 5 to 8 years, without Vitamin D supplementation, in different seasons of the year. VitD status was defined as sufficient with concentrations of 25OHVitD3 >20 ng/mL (50 nmol/L), insufficient 12-20 ng/mL (30-50 nmol/L) and deficient 20 ng/mL), which decreased significantly in winter to 54.3% (p <0.0001). CONCLUSIONS: In winter, 25OHVitD3 concentrations decreased in approximately half of the children, which was associated with an increase in PTH and ALP, and normal calcium concentrations. According to our results, children may need VitD supple mentation during fall and winter.

[Seasonal variations in 25-hydroxy vitamin D3, parathormone and alkaline phosphatase in school-aged children]. / Variación estacional de 25-hidroxi-vitamina D3, hormona paratiroidea y fosfatasa alcalina en niños escolares.

INTRODUCTION: The main role of Vitamin D is to regulate calcium metabolism, whose main source is vitamin D3 ob tained mostly from the action of ultraviolet (UV) light on the skin. OBJECTIVE: To evaluate the seaso nal differences in the concentrations of 25-hydroxy-vitamin D3 (25OHVitD3), parathyroid hormone (PTH), alkaline phosphatase (ALP), and calcium in school-age children. SUBJECTS AND METHOD: The concentrations of 25OHVitD3, PTH, ALP, and calcium were measured in children from Santiago, Chile (latitude -33.4372), aged 5 to 8 years, without Vitamin D supplementation, in different seasons of the year. VitD status was defined as sufficient with concentrations of 25OHVitD3 >20 ng/mL (50 nmol/L), insufficient 12-20 ng/mL (30-50 nmol/L) and deficient <12 ng/mL (30 nmol/L) based on the recommendations of the expert group of the "Global Consensus for the Prevention and Mana gement of Nutritional Rickets". RESULTS: 133 children participated (89 preterms under or equal to 32 weeks), 41 during summer, 28 in fall, 35 in winter, and 29 in spring. The difference of means between summer and winter was 9.6 ng/mL for 25OHVitD3 (p <0.0001), -11.1 pg/mL for PTH (p <0.0001), and -47.5 IU/mL for ALP (p= 0.01). There were no differences in calcium concentrations. In sum mer, 97.6% of the subjects were classified with sufficiency status (> 20 ng/mL), which decreased significantly in winter to 54.3% (p <0.0001). CONCLUSIONS: In winter, 25OHVitD3 concentrations decreased in approximately half of the children, which was associated with an increase in PTH and ALP, and normal calcium concentrations. According to our results, children may need VitD supple mentation during fall and winter.

ALS deficiency caused by an exon 2 deletion and a novel missense variant in the gene encoding ALS.

CONTEXT: ALS deficiency (ACLSD), caused by mutations in IGFALS, is characterized by a mild short stature, low concentrations of IGF-I and IGFBP-3, and a normal growth hormone (GH) stimulation test response. To our knowledge, no larger deletions have been reported. CASE DESCRIPTION: A 17-year-old adolescent male was evaluated due to delayed puberty and short stature. He had a height of 154.4 cm (SDS -2.84), a weight of 53.3 kg (SDS -1.41), a BMI of 22.4 kg/m2 (SDS +0.31), a Tanner 2 pubertal stage with a testicular volume of 10 mL, and a bone age of 16 years (SDS -1.33). After biochemical evaluation, low IGF-I levels, undetectable IGFBP-3 levels, and a normal response to the GH stimulation test were observed, suggesting GH insensitivity. ACLSD was confirmed by ALS measurement (116 ng/mL, SDS -3.19) and genetic analysis of IGFALS. An apparently homozygous missense variant, p. Pro624Leu, was found in exon 2 of the proband; this mutation was observed on one allele of the proband's father but was absent in the mother and siblings. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) was consistent with a deletion encompassing a significant part of exon 2 on one allele in the proband and in his mother and siblings. CONCLUSION: This is the first report of a large deletion in a patient with ACLSD. Deletion/duplication analysis should be considered in the genetic study of ACLSD, especially when homozygosity for a pathogenic variant cannot be confirmed by the study of the parents or when no variants are found but ALS concentrations are very low.