Repercusión del confinamiento por COVID-19 sobre el control glucémico en niños y adolescentes con diabetes mellitus tipo 1 / Impact of COVID-19 lockdown on glucemic control in children and adolescents with type 1 diabetes mellitus

Introducción y objetivos: Con objeto de hacer frente a la rápida propagación de la pandemia por coronavirus SARS-CoV-2, España decretó el confinamiento domiciliario de la población el 15 de marzo de 2020. El objetivo principal de este estudio es evaluar la repercusión de dicha medida sobre el control glucémico en niños y adolescentes con diabetes mellitus tipo 1 (DM1).Pacientes y métodos: Estudio observacional, retrospectivo, en niños y adolescentes con DM1 usuarios de sistemas de monitorización de glucosa intersticial. Se recogió la siguiente información correspondiente a las 2 últimas semanas de cuarentena, previas al inicio del desconfinamiento, para su posterior comparación con los datos de 2 semanas previas al confinamiento: necesidades diarias de insulina, glucosa intersticial media, HbA1c estimada, coeficiente de variación, tiempo en rango (70-180mg/dl), hipoglucemia (<70 y <54mg/dl) e hiperglucemia (>180 y>250mg/dl), uso del sensor y número de glucemias capilares. Mediante encuesta se obtuvo información acerca de rutinas de ingesta, ejercicio físico, necesidad de ajustes en la terapia, complicaciones agudas surgidas y acompañamiento de los pacientes por sus cuidadores durante el confinamiento. (AU)

Background and aims: To face the rapid spread of SARS-CoV-2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D).Patients and methods: Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl), and hyperglycemia (>180 and>250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications, and lockdown of caregivers were assessed via a survey. (AU)

Impact of COVID-19 lockdown on glucemic control in children and adolescents with type 1 diabetes mellitus.

BACKGROUND AND AIMS: To face the rapid spread of SARS-CoV2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D). PATIENTS AND METHODS: Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl) and hyperglycemia (>180 and> 250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications and lockdown of caregivers were assessed via a survey. RESULTS: 80 patients were studied (mean age 12.61±3.32 years, mean time of evolution of the disease 5.85±3.92 years), 66.2% treated with an insulin pump, users of following glucose monitoring systems: Guardian 3 (65%), FreeStyle Libre (18.8%) and Dexcom G6 (16.2%). Time in range in the cohort increased significantly during confinement (72.1±10.5 vs 74.8±10.5%; P=0.011) with lower time in hypoglycemia both <70mg/dl (4.6±3.2 vs 3.2±2.7%; P<0.001) and <54mg/dl (1.2±1.6 vs 0.7±1.2%; P<0.001) and hyperglycemia >250mg/dl (4.6±3.9 vs 3.7±3.7%; P=0.038). CV also decreased (35.8±6.3 vs 33.1±6.1%; P<0.001). Patients treated with multiple doses of insulin and poorer baseline glycemic control experienced greatest improvement. Daily insulin requirements remained stable. Regular practice of physical exercise and caregivers' confinement did not have a significant impact. CONCLUSIONS: Glycemic control in children and adolescents with T1D improved during quarantine, particularly in those with worse baseline control.

The impact of "faster aspart" on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump.

BACKGROUND AND AIMS: Post-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new "faster aspart" insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of "faster aspart" vs. "insulin aspart" in children and adolescents with DM1 on sensor-augmented pump treatment. PATIENTS AND METHODS: Multicentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) <70 and >180 mg/dL, mean sensor glucose pre- and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. RESULTS: The study included 32 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia >180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = .011) and >250 mg/dL (5.2±4.9 vs. 4.0 ± 3.6; p = .04), lower AUC >180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = .03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = .03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. CONCLUSIONS: Faster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies.

OBJECTIVE: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. DESIGN: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. METHODS: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. RESULTS: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. CONCLUSIONS: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

[Impact of COVID-19 lockdown on glucemic control in children and adolescents with type 1 diabetes mellitus]. / Repercusión del confinamiento por COVID-19 sobre el control glucémico en niños y adolescentes con diabetes mellitus tipo 1.

BACKGROUND AND AIMS: To face the rapid spread of SARS-CoV-2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D). PATIENTS AND METHODS: Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl), and hyperglycemia (>180 and>250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications, and lockdown of caregivers were assessed via a survey. RESULTS: 80 patients were studied (mean age 12.61±3.32 years, mean time of evolution of the disease 5.85±3.92 years), 66.2% treated with an insulin pump, users of following glucose monitoring systems: GuardianTM 3 (65%), FreeStyle LibreTM (18.8%) and Dexcom G6TM (16.2%). Time in range in the cohort increased significantly during confinement (72.1±10.5 vs. 74.8±10.5%; P=.011) with lower time in hypoglycemia both<70mg/dl (4.6±3.2 vs. 3.2±2.7%; P<.001) and<54mg/dl (1.2±1.6 vs. 0.7±1.2%; p<0.001) and hyperglycemia >250mg/dl (4.6±3.9 vs. 3.7±3.7%; P=.038). CV also decreased (35.8±6.3 vs. 33.1±6.1%; P<.001). Patients treated with multiple doses of insulin and poorer baseline glycemic control experienced greatest improvement. Daily insulin requirements remained stable. Regular practice of physical exercise and caregivers' confinement did not have a significant impact. CONCLUSIONS: Glycemic control in children and adolescents with T1D improved during quarantine, particularly in those with worse baseline control.

[The impact of «faster aspart¼ on blood glucose control in children and adolescents with type 1 diabetes treated using a sensor-augmented insulin pump]. / Impacto de faster aspart sobre el control glucémico en niños y adolescentes con diabetes tipo 1 en tratamiento con un sistema integrado.

BACKGROUND AND AIMS: Post-prandial glucose control is essential to achieve metabolic goals in patients with type 1 diabetes mellitus (T1DM). The new «faster aspart¼ insulin has a pharmacological profile noted for its faster absorption and onset of action, and increased early availability, resulting in improved blood glucose control after meals. The main objective of the study was to analyse the efficacy of «faster aspart¼ vs. «insulin aspart¼ in children and adolescents with DM1 on sensor-augmented pump treatment. PATIENTS AND METHODS: Multicentre, longitudinal and prospective analytical trial evaluating the use of faster aspart insulin for three months in children with T1DM with MiniMed640G® sensor-augmented pumps previously treated with aspart insulin. At the beginning and end of the study the following variables were analysed for subsequent comparison: mean sensor glucose, percentage of time in range, hypoglycaemia and hyperglycaemia, area under the curve (AUC) < 70 and > 180 mg/dL, mean sensor glucose pre and postprandial in main meals, daily insulin requirements, basal/bolus percentage, and HbA1c. Acute complications, adverse events and satisfaction survey were assessed. RESULTS: The study included 31 patients with a mean of 13.49 ± 2.42 years of age and with T1DM of 7.0 ± 3.67 years of onset. The use of faster aspart was associated with lower time in hyperglycaemia > 180 mg/dL (25.8 ± 11.3 vs. 22.4 ± 9.5; p = 0.011) and > 250 mg/dL (5.2 ± 4.9 vs. 4.0 ± 3.6; p = 0.04), lower AUC > 180 mg/dL (10.8 ± 6.5 vs. 9.3 ± 6.1; p = 0.03), and increased time in range (71.4 ± 10.0 vs. 74.3 ± 9.2; p = 0.03). No significant changes in hypoglycaemia, HbA1c, insulin requirements, and basal/bolus percentages were detected. Faster aspart was safe and well-evaluated by patients and caregivers. CONCLUSIONS: Faster aspart achieves better glycaemic control by increasing glucose time in range in children and adolescents with T1DM on treatment with sensor-augmented pumps.

RIT1: un nuevo gen causal del síndrome de Noonan / RIT1: a novel gene associated with Noonan syndrome

Introducción. El síndrome de Noonan es el más frecuente del grupo de los síndromes malformativos congénitos originados por mutaciones germinales en genes de la vía RAS/MAPK, denominados genéricamente RAS-opatías, uno de los grupos más comunes de alteraciones genéticas congénitas en la práctica clínica. Recientemente se han descrito mutaciones en el gen RIT1 en pacientes con síndrome de Noonan. Caso clínico. Niña de 7 años con diagnóstico clínico de síndrome de Noonan, que entre sus manifestaciones clínicas incluye miocardiopatía hipertrófica, en la que se ha identificado una mutación de novo en heterocigosis, en RIT1, c.295T>C (p.Phe99Leu), no descrita previamente, probablemente causal. Conclusiones. RIT1 comparte homología con otras proteínas RAS y la expresión de alelos mutantes origina un efecto de ganancia de función que apoya su papel causal en el síndrome de Noonan. Podemos estimar actualmente que es responsable de un 3-5% de los casos del síndrome. Estos casos con síndrome de Noonan, respecto a los que presentan mutaciones en otros genes, se caracterizan por una mayor frecuencia de alteraciones prenatales, alta frecuencia de miocardiopatía hipertrófica y menor frecuencia de talla baja y deformidad torácica. Destaca la importancia de incorporar los nuevos genes identificados en los paneles diagnósticos (AU)

Introduction. Noonan syndrome is the most frequent of the congenital group of malformation syndromes caused by germline mutations that encode components of the RAS/MAPK pathway, termed RASopathies, one of the most frequent congenital genetic disorders in the clinical practice. Recently RIT1 mutations have been reported in patients with Noonan syndrome. Case report. A 7 years-old girl with a clinical diagnosis of Noonan syndrome, and with a hypertrophic cardiomyopathy included in her clinical manifestations, where a de novo heterozygous, probably pathogenic, novel mutation in RIT1, c.295T>C (p.Phe99Leu), has been identified. Conclusions. RIT1 shares homology with other RAS proteins and the expression of mutant alleles demonstrates a gain-offunction effect supporting a causative role in Noonan syndrome pathogenesis. Data suggest that the frequency of RIT1 mutations can be estimated as 3-5% in Noonan syndrome patients. These cases compared with Noonan patients harboring mutations in other genes are characterized by high frequency of prenatal abnormalities and hypertrophic cardiomyopathy, and lower frequencies of short stature and pectus abnormalities. We emphasize the importance of the novel identified genes in order to be included in the diagnostic panels (AU)