Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: The Dapa-ON multicenter retrospective study.

OBJECTIVE: To assess real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes mellitus (T1DM). METHODS: We conducted a multicenter retrospective study in Spain including data from 250 people living with T1DM receiving dapagliflozin as add-on therapy to insulin (80.8 % on-label use). The number of diabetic ketoacidosis (DKA) events was calculated over a 12-month follow-up (primary outcome). Changes in body weight, HbA1c, total daily insulin dose, and continuous glucose monitoring (CGM) metrics from baseline (at dapagliflozin prescription) to 12 months were also evaluated. RESULTS: A total of five DKA events (2.4 % [95 % CI 0.3;4.5] were reported in patients with a 12-month follow-up, n = 207): two events related to insulin pump malfunction, two events related to concomitant illnesses, and one event related to insulin dose omission. DKA events were more frequent among insulin pump users than among participants on multiple daily injections (7.7 % versus 1.2 %). Four of the reported DKA events occurred within the first six months after initiation of dapagliflozin. No deaths or persistent sequelae due to DKA were reported. No severe hypoglycemia episodes were reported. Significant reductions in mean body weight (-3.3 kg), HbA1c (-0.6 %), and total daily insulin dose (-8.6 %), P < 0.001, were observed 12 months after dapagliflozin prescription. Significant improvements in TIR (+9.3 %), TAR (-7.2 %), TBR (-2.5 %), and coefficient of variation (-5.1 %), P < 0.001, were also observed in the subgroup of patients with available CGM data. Finally, an improvement in urinary albumin-to-creatinine ratio (UACR) was found among participants with UACR ≥ 30 mg/g at baseline (median decrease of 99 mg/g in UACR, P = 0.001). CONCLUSION: The use of dapagliflozin in people living with T1DM has an appropriate safety profile after careful selection of participants and implementation of strategies to reduce the risk of DKA (i.e., prescribed according to the recommendations of the European Medicines Agency), and also leads to clinical improvements in this population.

Síndrome de Apert: Acrocefalosindactilia, Caso Clínico / Apert Syndrome: Acrocephalosyndactyly, Clinical Case

Introducción:El síndrome de Apert tiene una incidencia variable. Se ha estimado una prevalencia de 1:160milnacimientos. Es de herencia autosómica dominante y se han encontrado algunos factores relacionados, como edad paterna avanzada. Caso:Niña, recién nacida a término, con dificultad respiratoria, hipotonía, sindactiliay retardo del neurodesarrollo. Con Tomografía de Senos paranasales se reportó una malformación del canal semicircular lateral y del vestíbulo bilateral, se confirmó la presencia de una estenosis nasal derecha con desviación septal hacia la derecha y la presencia de estenosis bilateral de coanas. Con una TAC de cráneo se reportó Plagiocefalia unilateral izquierdaylapresencia de craneosinostosis. Evolución: En hospitalización se logró el retiro del oxígeno suplementario, recibió terapia miofuncional con lo que toleró adecuadamente la alimentación oral y se programó la corrección de estenosis de coanas en forma ambulatoria la cual se realizó a los 14 meses. A los18 meses se realizó la cirugía de corrección de craneosinostosis con un avance fronto-orbitario, durante el período post-operatorio la paciente desarrolló una neumonía que fue tratada con antibióticos. Al resolverse el cuadro, fue dada de alta. Conclusión:el Síndrome de Apert, un desorden congénito caracterizado por craneosinostosis coronal, sindactilia simétrica en las cuatro extremidades y malformaciones craneofaciales. El diagnóstico es clínico.El tratamiento es sintomático, relacionado con las diferentes malformaciones asociadas y se debe realizar un manejo interdisciplinario

Introduction: Apert syndrome has a variable incidence. A prevalence of 1: 160 thousand births has been estimated. It is autosomal dominant and some related factors have been found, such as advanced paternal age. Case: Girl, newborn at term, with respiratory distress, hypotonia, syndactyly and neurodevelopmental delay. With Paranasal Sinus Tomography, a malformation of the lateral semicircular canal and the bilateral vestibule was reported, the presence of a right nasal stenosis with septal deviation to the right and the presence of bilateral choanal stenosis was confirmed. With a CT of the skull, left unilateral plagiocephaly and the presence of craniosynostosis were reported. Evolution: In hospitalization, the withdrawal of supplemental oxygen was achieved, he received myofunctional therapy with which he tolerated oral feeding adequately and the correction of choanal stenosis was scheduled on an outpatient basis, which was performed at 14 months. At 18 months, craniosynostosis correction surgery was performed with a fronto-orbital advance, during the postoperative period the patient developed pneumonia that was treated with antibiotics. When the picture was resolved, she was discharged. Conclusion: Apert Syndrome, a congenital disorder characterized by coronal craniosynostosis, symmetric syndactyly in all four limbs, and craniofacial malformations. The diagnosis is clinical. Treatment is symptomatic, related to the different associated malformations and interdisciplinary management must be carried out

Implication of gestational diabetes treatment on maternal weight gain and low neonatal weight: a large retrospective cohort study.

INTRODUCTION: Objective: the treatment for gestational diabetes is based on diet, and this may modify maternal weight gain. The limited maternal weight gain is related to newborns with small weight for their gestational age (SGA), and many studies have found an increase of SGA in women with gestational diabetes (GD), but the reason for this is not clear. The objective of this study is to evaluate the effects of gestational diabetes treatment on maternal weight gain and neonatal weight. Methods: a retrospective cohort study of 1,765 patients with GD, according to the National Diabetes Data Group (NDDG) criteria. We assessed: pre-pregnancy BMI, total maternal weight gain (MWG), weight gain during the third trimester, gestational week of starting the treatment, and treatment modality (diet or diet plus insulin). Birth weight was adjusted by gestational age and gender: SGA (≤ 10th) and large for gestational age (LGA) (> 90th). Results: the percentage of newborns with weight ≤ 10 was 14.8 %. The diet and the time of initiation of the treatment were related to maternal weight gain (MWG) in the third trimester. For every 1 kcal/kg of variation in the diet (increase or decrease), a MWG variation of 0.03 (0.001-0.06) kg occurred (p < 0.01). For each week before the beginning of treatment, the mother did not gain 0.13 ± [(-0.15) - (-0.11)] kg in the third trimester (p < 0.01). The SGA was related to the lowest MWG in total gestation: 7.0 (IQR 3.0-10.4) kg vs 8.4 (IQR 5.0-11.6) kg (p < 0.01), and in the third trimester: 0.3 (IQR -0.9-1.5) kg vs. 0.9 (IQR -0.3-2.2) kg (p < 0.01). Conclusion: the dietary treatment for gestational diabetes leads to a lower maternal weight gain and induces an impact on neonatal weight.

INTRODUCCIÓN: Objetivo: el tratamiento para la diabetes gestacional se basa en la dieta y esto puede modificar el aumento de peso materno. Un aumento de peso materno limitado está relacionado con recién nacidos con bajo peso para su edad gestacional (SGA). Muchos estudios han encontrado un aumento de niños con bajo peso en mujeres con diabetes gestacional, pero la razón no está clara. El objetivo es evaluar los efectos del tratamiento de la diabetes gestacional sobre el aumento de peso materno y el peso neonatal. Métodos: estudio de cohortes retrospectivo en 1765 pacientes con diabetes gestacional. Evaluamos: IMC antes del embarazo, aumento de peso materno total, aumento de peso durante tercer trimestre, semana gestacional de inicio y modalidad de tratamiento (dieta o dieta más insulina). El peso al nacer se ajustó por edad gestacional y género: SGA (≤ 10) y grande para la edad gestacional (> 90). Resultados: el porcentaje de recién nacidos con peso ≤ 10 fue 14,8%. La dieta y el momento de inicio del tratamiento se relacionaron con aumento de peso materno en el tercer trimestre. Por cada 1 kcal/kg de variación en dieta (aumento o disminución) se produjo una variación de aumento del peso materno de 0,03 (0,001-0,06) kg (p < 0,01). Por cada semana antes de inicio del tratamiento la madre dejó de ganar 0,13 ± [(- 0,15)-(- 0,11)] kg en el tercer trimestre (p < 0,01). El SGA se relacionó con un aumento de peso materno más bajo en el total de la gestación: 7,0 (IQR 3,0-10,4) kg versus 8,4 (IQR 5,0-11,6) kg (p < 0,01), y en el tercer trimestre: 0,3 (IQR -0,9-1,5) kg vs. 0,9 (IQR -0,3-2,2) kg (p < 0,01). Conclusión: el tratamiento dietético para la diabetes gestacional puede conducir a un menor aumento de peso materno y a su influir en el peso neonatal.

[Prevalence of carbohydrate metabolism disturbances in a population of children and adolescents with severe obesity]. / Prevalencia de alteraciones del metabolismo hidrocarbonado en una población infanto-juvenil con obesidad grave.

INTRODUCTION: There is currently a disproportionate increase in childhood and adolescent obesity worldwide, together with other disorders involving substantial cardiometabolic risk in adulthood, such as alterations in carbohydrate metabolism. OBJECTIVE: To establish the prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) after an oral glucose tolerance test, and the prevalence of type 2 diabetes mellitus (DM-2) in a pediatric population with severe obesity. Additionally, we aimed to assess clinical metabolic differences between prediabetic obese patients and obese subjects without prediabetes. MATERIAL AND METHODS: A cross-sectional study was carried out in children and adolescents with severe obesity (>97th percentile). The variables studied were age, sex, height, weight, body mass index, waist circumference, fasting plasma glucose and oral glucose tolerance test, insulinemia, insulin resistance assessed by the homeostasis model assessment (HOMA) index, glycated hemoglobin (HbA(1c)), triglycerides, high-density lipoprotein cholesterol (HDL), and systolic and diastolic blood pressure. RESULTS: A total of 133 patients were included: 67 boys (50.4%) and 66 girls (49.6%), with a mean age of 12.17±3.27 years. Fourteen patients (10.52%) had prediabetes (10 IFG, 3 IGT, 1 IFG+IGT): 7 girls and 8 boys, with a mean age of 13.2±3.3 years. One patient had DM2 (0.75%). Patients with prediabetes had significantly higher concentrations of fasting glucose (98±10.76 vs 88.53±6.3mg/d; p=0.001), insulinemia (35.38±14.22 vs 22.95±14.30µU/ml; p=0.009) and HOMA index (8.10±3.24 vs 4.89±3.27; p=0.004) than patients without impaired carbohydrate metabolism. These patients also had higher values of HbA(1c), triglycerides, blood pressure and HDL concentrations, although differences were not statistically significant. CONCLUSIONS: The prevalence of prediabetes (IFG/IGT) in children with severe obesity was high (10.52%). These patients should therefore be investigated to establish early diagnosis and appropriate treatment. Obese patients with prediabetes have significantly higher levels of insulin and insulin resistance than individuals without impaired carbohydrate metabolism.

[Effects of zoledronic acid in adults with osteogenesis imperfecta]. / Efectos del tratamiento con ácido zoledrónico en pacientes adultos con osteogénesis imperfecta.

BACKGROUND AND OBJECTIVE: Osteogenesis imperfecta (OI) is a genetic disorder that results in bone fragility. Several studies have demonstrated the effectiveness of bisphosphonate therapy. The aim of this study was to evaluate the effects of intravenous zoledronic acid on bone mineral density (BMD) and biochemical markers of bone turnover in adults with OI. MATERIAL AND METHODS: We carried out a prospective non-randomized study in patients with osteoporosis or severe osteopenia (T score < -2) related to OI and intolerance or contraindication to oral bisphosphonates. The patients were treated with a zoledronic acid infusion every 6 months. Densitometry was carried out annually. Calcium (Ca), phosphate (P), intact parathormone (PTH), 25 hydroxyvitamin D and biochemical markers of bone turnover [bone alkaline phosphatase (BAP), beta-cross-laps (CTX) and urinary deoxypyridoxine (DOP)] were measured every year. Adverse events and new fractures were registered. RESULTS: Ten patients (2 men and 8 women) were treated. Treatment increased BMD measured in the lumbar spine after 24 (0.738+/-0.141 vs 0.788+/-0.144 g/cm(2); p=0.048) and 36 months (0.720+/-0.139 vs 0.820+/-0.128; p=0.01). Significant increases in BMD were also observed after 24 months in the femoral neck (0.677+/-0.121 vs 0.703+/-0.122 g/cm(2); p<0.016). Serum Ca, P, BAP and CTX concentrations remained unchanged. PTH concentrations increased and vitamin D concentrations decreased after 36 months of treatment. DOP excretion decreased significantly after 24 months. Seven patients had mild influenza-like symptoms occurring within the first 24 h after the first infusion. No severe adverse events were observed. None of the patients had new fractures. CONCLUSION: Zoledronic acid seems to be a safe and effective treatment option in adults with osteoporosis related to OI.