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Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy. Methods: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). Results: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis. Conclusion: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.
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Testes Respiratórios , Cetoacidose Diabética , Insulina , Humanos , Cetoacidose Diabética/metabolismo , Testes Respiratórios/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Insulina/metabolismo , Estudos de Viabilidade , Hidratação/métodos , Idoso , Biomarcadores/metabolismo , Biomarcadores/análise , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Background: The overarching goal of blood glucose forecasting is to assist individuals with type 1 diabetes (T1D) in avoiding hyper- or hypoglycemic conditions. While deep learning approaches have shown promising results for blood glucose forecasting in adults with T1D, it is not known if these results generalize to children. Possible reasons are physical activity (PA), which is often unplanned in children, as well as age and development of a child, which both have an effect on the blood glucose level. Materials and Methods: In this study, we collected time series measurements of glucose levels, carbohydrate intake, insulin-dosing and physical activity from children with T1D for one week in an ethics approved prospective observational study, which included daily physical activities. We investigate the performance of state-of-the-art deep learning methods for adult data-(dilated) recurrent neural networks and a transformer-on our dataset for short-term (30 min) and long-term (2 h) prediction. We propose to integrate static patient characteristics, such as age, gender, BMI, and percentage of basal insulin, to account for the heterogeneity of our study group. Results: Integrating static patient characteristics (SPC) proves beneficial, especially for short-term prediction. LSTMs and GRUs with SPC perform best for a prediction horizon of 30 min (RMSE of 1.66 mmol/l), a vanilla RNN with SPC performs best across different prediction horizons, while the performance significantly decays for long-term prediction. For prediction during the night, the best method improves to an RMSE of 1.50 mmol/l. Overall, the results for our baselines and RNN models indicate that blood glucose forecasting for children conducting regular physical activity is more challenging than for previously studied adult data. Conclusion: We find that integrating static data improves the performance of deep-learning architectures for blood glucose forecasting of children with T1D and achieves promising results for short-term prediction. Despite these improvements, additional clinical studies are warranted to extend forecasting to longer-term prediction horizons.
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While advancements in the treatment of diabetes continue to rapidly evolve, many of the newer technologies have financial barriers to care, opposing the egalitarian ethos of Banting who sold his patent on insulin for a nominal cost to allow it to be made widely available. Inequity in access to new therapies drives disparity in diabetes burden with potential for these gaps to widen in the future. The 2023 International Conference on Advanced Technologies and Treatments of Diabetes (ATTD) presented ground-breaking and current research in diabetes technology. Oral presentations of the ATTD conference 2023 were analyzed to describe what percentage of speakers discussed equity in their talks. Overall, less than a quarter of presenters discussed equity, though there was regional variation. To ensure that diabetes technologies reduce disparity and improve outcomes, we encourage future speakers at diabetes (technology) conferences to consider equity of diabetes care and incorporate this into their presentations.
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Diabetes Mellitus , Humanos , Diabetes Mellitus/terapia , InsulinaRESUMO
Accurate treatment adjustment to physical activity (PA) remains a challenging problem in type 1 diabetes (T1D) management. Exercise-driven effects on glucose metabolism depend strongly on duration and intensity of the activity, and are highly variable between patients. In-silico evaluation can support the development of improved treatment strategies, and can facilitate personalized treatment optimization. This requires models of the glucose-insulin system that capture relevant exercise-related processes. We developed a model of glucose-insulin regulation that describes changes in glucose metabolism for aerobic moderate- to high-intensity PA of short and prolonged duration. In particular, we incorporated the insulin-independent increase in glucose uptake and production, including glycogen depletion, and the prolonged rise in insulin sensitivity. The model further includes meal absorption and insulin kinetics, allowing simulation of everyday scenarios. The model accurately predicts glucose dynamics for varying PA scenarios in a range of independent validation data sets, and full-day simulations with PA of different timing, duration and intensity agree with clinical observations. We personalized the model on data from a multi-day free-living study of children with T1D by adjusting a small number of model parameters to each child. To assess the use of the personalized models for individual treatment evaluation, we compared subject-specific treatment options for PA management in replay simulations of the recorded data with altered meal, insulin and PA inputs.
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Diabetes Mellitus Tipo 1 , Humanos , Criança , Adulto , Glicemia/metabolismo , Medicina de Precisão , Exercício Físico/fisiologia , Glucose , Insulina , Hipoglicemiantes/uso terapêuticoRESUMO
Diabetic ketoacidosis (DKA), a frequent complication of type 1 diabetes (T1D), is characterized by hyperosmolar hypovolemia. The response of water-regulating hormones arginine vasopressin (AVP; antidiuretic hormone) and aldosterone to DKA treatment in children is not well understood, although they may have potential as future diagnostic, prognostic, and/or treatment monitoring markers in diabetic patients. We aimed to characterize the dynamics of the response in copeptin (marker for AVP) and aldosterone secretion to rehydration treatment in pediatric patients with DKA. Data originated from a prospective, observational, multicenter study including 28 pediatric T1D patients treated for DKA (median age, 11.5 years; weight, 35 kg). Serial measurements of hormone levels were obtained during 72 h following rehydration start. Semimechanistic pharmacometric modeling was used to analyze the kinetic/dynamic relationship of copeptin and aldosterone secretion in response to the correction of hyperosmolality and hypovolemia, respectively. Modeling revealed different sensitivities for osmolality-dependent copeptin secretion during the first 72 h of rehydration, possibly explained by an osmotic shift introduced by hypovolemia. Response in aldosterone secretion to the correction of hypovolemia seemed to be delayed, which was well described by an extra upstream turnover compartment, possibly representing chronic upregulation of aldosterone synthase (cytochrome P450 11B2). In conclusion, semimechanistic modeling provided novel physiological insights in hormonal water regulation in pediatric patients during DKA treatment, providing rationale to further evaluate the potential of monitoring copeptin, but not aldosterone due to its delayed response, for future optimization of rehydration treatment to reduce the risk of acute complications such as cerebral edema.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Humanos , Criança , Cetoacidose Diabética/terapia , Cetoacidose Diabética/complicações , Diabetes Mellitus Tipo 1/complicações , Hipovolemia/complicações , Estudos Prospectivos , Hidratação/efeitos adversosRESUMO
Introduction: It is crucial to understand psychosocial outcomes in children and adolescents with type 1 diabetes (T1D) and their families to provide optimal family-centered care. Hence, the aim of this study was to explore psychosocial outcomes in young people with T1D and their parents using currently available glucose monitoring devices in a real-life clinic setting. Methods: Children and adolescents aged 2-18 years with T1D for more than 6 months and their parents were recruited into a cross-sectional study to complete the Hypoglycemia Fear Survey (HFS) and the Pediatric Quality of Life Inventory (PedsQL) Generic Score Scales, Diabetes Module and Family Impact Module. Demographics and diabetes-specific parameters were obtained from medicals records. Results: Fifty-nine children and adolescents (mean age 15.1 ± 3.0 years) and 49 parents of children (mean age of children 12.5± 3.3 years) of which 44 were child-parent dyads completed the questionnaires. Parents had a higher mean (SD) FOH total and worry subscore than children, total score was 37.9 (14.6) vs. 32.2 (11.9), p = 0.047 and worry subscore was 17.8 (10.4) vs. 12.8 (9.0), p = 0.01. Furthermore, lower parental diabetes-specific QoL score was observed in parents, 78.8 (12.2) vs. 82.7 (10.3), p=0.02. No difference in FOH and QoL between real-time continuous glucose monitoring (rtCGM) and intermittently scanned glucose monitoring (isCGM) users and users of devices with and without alerts was observed. In isCGM users (n=36 completing the child questionnaires, n=33 completing parent questionnaires), higher parental FOH and lower parental diabetes-specific QoL correlated with higher scanning frequency, r = 0.399, p = 0.021, and r = -0.464, p = 0.007 respectively. No significant correlation was documented between scanning frequency and child questionnaire scores. Conclusions: Parents are more likely to perceive higher levels of psychosocial burden related to their child's diabetes than children and adolescents with T1D, especially parents of younger children. This highlights the need for family-based education and treatment resources to support parents in diabetes management in addition to rapidly advancing diabetes technology. In isCGM users, higher parental FOH and lower parent-perceived QoL correlated with a higher scanning frequency, indicating the potential impact of glucose monitoring modality on psychosocial outcomes or vice versa.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Adolescente , Glicemia , Automonitorização da Glicemia , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/psicologia , Medo/psicologia , Humanos , Pais/psicologia , Qualidade de VidaRESUMO
OBJECTIVE: To determine if the relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio (ICR) required to maintain glycaemia is linear in people with type 1 diabetes. METHODS: We used an open labelled randomized four-arm cross-over study design. Participants (N = 31) aged 12-27 years, HbA1c ≤ 64 mmol/mol (8.0%) received insulin doses based on the individual's ICR and the study breakfast carbohydrate quantity and then consumed four breakfasts containing 20, 50, 100 and 150 g of carbohydrate over four consecutive days in randomized order. The breakfast fat and protein percentages were standardized. Postprandial glycaemia was assessed by 5 h continuous glucose monitoring. The primary outcome was percent time in range (TIR) and secondary outcomes included hypoglycaemia, glucose excursion and incremental area under the curve. Statistical analysis included linear mixed modelling and Wilcoxon signed rank tests. RESULTS: The 20 g carbohydrate breakfast had the largest proportion of TIR (0.74 ± 0.29 p < 0.04). Hypoglycaemia was more frequent in the 50 g (n = 13, 42%) and 100 g (n = 15, 50%) breakfasts compared to the 20 g (n = 6, 20%) and 150 g (n = 7, 26%) breakfasts (p < 0.029). The 150 g breakfast glucose excursion pattern was different from the smaller breakfasts with the lowest glucose excursion 0-2 h and the highest excursion from 3.5 to 5 h. CONCLUSIONS: A non-linear relationship between insulin requirement and breakfast carbohydrate content was observed, suggesting that strengthened ICRs are needed for meals with ≤20 and ≥150 g of carbohydrate. Meals with ≥150 g of carbohydrate may benefit from dual wave bolusing.
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Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Desjejum/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Carboidratos da Dieta/farmacologia , Insulina/farmacologia , Refeições/fisiologia , Adolescente , Adulto , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Adulto JovemRESUMO
Regular exercise is beneficial and recommended for people with type 1 diabetes, but increased glucose demand and changes in insulin sensitivity require treatment adjustments to prevent exercise-induced hypoglycemia. Several different adjustment strategies based on insulin bolus reductions and additional carbohydrate intake have been proposed, but large inter- and intraindividual variability and studies using different exercise duration, intensity, and timing impede a direct comparison of their effects. In this study, we use a mathematical model of the glucoregulatory system and implement published guidelines and strategies in-silico to provide a direct comparison on a single 'typical' person on a standard day with three meals. We augment this day by a broad range of exercise scenarios combining different intensity and duration of the exercise session, and different timing with respect to adjacent meals. We compare the resulting blood glucose trajectories and use summary measures to evaluate the time-in-range and risk scores for hypo- and hyperglycemic events for each simulation scenario, and to determine factors that impede prevention of hypoglycemia events. Our simulations suggest that the considered strategies and guidelines successfully minimize the risk for acute hypoglycemia. At the same time, all adjustments substantially increase the risk of late-onset hypoglycemia compared to no adjustment in many cases. We also find that timing between exercise and meals and additional carbohydrate intake during exercise can lead to non-intuitive behavior due to superposition of meal- and exercise-related glucose dynamics. Increased insulin sensitivity appears as a major driver of non-acute hypoglycemic events. Overall, our results indicate that further treatment adjustment might be required both immediately following exercise and up to several hours later, but that the intricate interplay between different dynamics makes it difficult to provide generic recommendations. However, our simulation scenarios extend substantially beyond the original scope of each model component and proper model validation is warranted before applying our in-silico results in a clinical setting.
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Simulação por Computador , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cálculos da Dosagem de Medicamento , Exercício Físico/fisiologia , Insulina/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Carboidratos da Dieta/administração & dosagem , Fidelidade a Diretrizes , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Resistência à Insulina , Refeições , Modelos Teóricos , Medicina de Precisão/métodosRESUMO
BACKGROUND: Hypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia. OBJECTIVE: To evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D. METHODS: Children and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia. RESULTS: Mean QTc during hypoglycemia was significantly longer compared to euglycemia (412 ± 15 vs. 405 ± 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 ± 57 to 73 ± 43 ms) and HF (from 54 ± 17 to 47 ± 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 ± 9 to 72 ± 12 bpm) and LF (from 44 ± 17 to 52 ± 21 nu) increased (p = 0.04). CONCLUSION: A QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction.
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Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Frequência Cardíaca/fisiologia , Coração/fisiopatologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/fisiopatologia , Adolescente , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Eletrocardiografia Ambulatorial , Feminino , Humanos , Insulina/efeitos adversos , Insulina/uso terapêutico , Masculino , Estudos ProspectivosRESUMO
Objective: This study evaluated the efficacy of using a hybrid closed loop (HCL) system in restoring hypoglycemia awareness in individuals with impaired awareness of hypoglycemia (IAH). Research Design and Methods: Participants with IAH (Gold score ≥4) were recruited into a randomized crossover pilot study. They participated in two 8-week periods using a HCL system (Medtronic 670G™) (intervention) and standard insulin pump therapy (control). Hyperinsulinemic hypoglycemic clamp studies were undertaken at baseline and at the end of each study period for the evaluation of the counter-regulatory hormonal and symptomatic responses to hypoglycemia. Results: Seventeen participants (mean age [standard deviation] 35.8 years [11.2 years]) were included in the study. Peak epinephrine levels (median, interquartile range [IQR]) in response to hypoglycemia were similar postintervention and control periods; 234.7 pmol/L (109.2; 938.9) versus 188.3 pmol/L (133.7; 402.9), P = 0.233. However, both peak adrenergic and neuroglycopenic symptom scores were higher after intervention; 5.0 (4.5; 9.0) versus 4.0 (4.0; 5.5), P = 0.009, and 8.5 (6.0; 15.0) versus 6.5 (6.0; 7.0) P = 0.014, respectively. Self-reported hypoglycemia awareness improved: median (IQR) Gold score was 4.0 (3.0; 5.5) versus 5.5 (4.5; 6.0); intervention versus control, P = 0.033. Time spent <3.9 and <3.0 mmol/L was lower in the intervention group than in control, P = 0.002. Other patient-reported outcomes (hypoglycemia fear and diabetes treatment satisfaction) did not change. Conclusions: A short-term use of a HCL system failed to demonstrate an improvement in counter-regulatory hormonal responses. However, higher hypoglycemia symptom scores during controlled hypoglycemia, better self-reported hypoglycemia awareness, and less time spent in hypoglycemia suggest the potential benefits of a HCL system in people with IAH. Trial Registration: anzctr.org.au Identifier: ACTRN12616000909426.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Projetos PilotoRESUMO
CONTEXT: Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). OBJECTIVE: The objective of this work is to characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA. DESIGN AND SETTING: A prospective, observational, multicenter study was conducted. PATIENTS AND INTERVENTION: Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. MAIN OUTCOME MEASURES: Measurements included temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), and association between-subject variability (BSV) (coefficient of variation, CV%). RESULTS: Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95 pmol/L (95% CI, 55-136 pmol/L) (CV%, 158%) to 9.7 pmol/L (95% CI, 8.1-11.4 pmol/L) (CV%, 31%) with a 50% recovery time (t1/2) of 7.1 hours (range, 5.1-11.5 hours) (114%). Serum osmolality decreased from 321 mOsm/kg (range, 315-327 mOsm/kg) (4%) to 294 mOsm/kg (range, 292-296 mOsm/kg) (1%) with a t1/2 of 4.3 hours (range, 3.0-5.6 hours) (64%). Copeptin levels doubled with each osmolality increase by 15 mOsm/kg (range, 10-21 mOsm/kg) (59%), from 9.8 pmol/L (range, 7.3-12.3 pmol/L) (48%) to 280 mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (Pâ =â .001), and less between mild vs moderate-severe DKA (Pâ =â .04). CONCLUSIONS: First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.
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Cetoacidose Diabética/terapia , Hidratação , Glicopeptídeos/sangue , Adolescente , Arginina Vasopressina/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Cetoacidose Diabética/sangue , Feminino , Humanos , Lactente , Masculino , Concentração Osmolar , Estudos ProspectivosRESUMO
Background: In April 2017, the Australian Government announced the full subsidy of continuous glucose monitors (CGM) to children and young people <21 years with type 1 diabetes (T1D). This study aimed to evaluate the effect of CGM on psychosocial outcomes in a T1D pediatric population-based sample. Methods: Children with T1D, commencing CGM between June 2017 and January 2018, and their parents were recruited in a prospective cohort study in a tertiary pediatric hospital in Western Australia. Parents and children older than 12 years self-completed questionnaires at onset of CGM and 2 months later, on fear of hypoglycemia (FOH) and diabetes treatment satisfaction (DTS). Parents provided measures of sleep quality. Children completed the Gold hypoglycemia awareness score. Hemoglobin A1c (HbA1c) values were compared at baseline (BL) and follow-up (FU). Results: Sixty parents and 38 children provided measures at BL and FU. Parental total FOH decreased (mean score BL vs. FU; 50.0 vs. 44.3, P = 0.004) with reduction in the Worry subscore (28.2 vs. 24.2, P = 0.004). Furthermore, parental and child DTS increased. Parental sleep quality improved (P < 0.001) and overnight finger prick testing decreased (P < 0.001). Impaired hypoglycemic awareness decreased in children (26.3% vs. 10.5%, P = 0.031). HbA1c reduced from 8.4% (68 mmol/mol) to 8.1% (65 mmol/mol) (P = 0.036). Conclusions: Introduction of subsidized CGM showed early improvement in psychosocial and glycemic outcomes in patients and their families in Western Australia. Ongoing evaluation is essential to assess whether equitable access to CGM will translate to sustained benefits for Australian T1D pediatric patients.
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Glicemia/análise , Diabetes Mellitus Tipo 1/psicologia , Hipoglicemia/psicologia , Pais/psicologia , Dispositivos Eletrônicos Vestíveis/psicologia , Adolescente , Automonitorização da Glicemia/economia , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/economia , Feminino , Financiamento Governamental , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Masculino , Estudos Prospectivos , Sono , Dispositivos Eletrônicos Vestíveis/economia , Austrália OcidentalRESUMO
Diabetes care during exercise frequently requires interruptions to activity and adds extra challenges particularly for young individuals with type 1 diabetes (T1D). This study investigated the use of a carbohydrate (CHO) intake algorithm based on continuous glucose monitoring (CGM) trends during physical activity. Children with T1D diagnosed for >1 year, ages 8-12 years, with a glycated hemoglobin of <10% were recruited into a randomized crossover study. They attended two similar mornings of fun-based physical activity and adhered to either a CHO intake algorithm based on CGM trends (intervention) or to standard exercise guidelines (consumption of 0.5 g CHO/kg/h when glucose <8 mmol/L) (control). Outcome measures included events such as exercise interruptions, CHO intake, and hypoglycemia events and percentage time spent in different sensor glucose ranges. Fourteen children completed the study. No episodes of significant hypoglycemia (sensor glucose level <3.0 mmol/L) occurred in either arm. Mean CHO intake was the same in both arms, 0.3 ± 0.2 g/kg/h. However, the intervention algorithm resulted in fewer CHO intake events per day: rate [95% confidence interval] 2.4 [1.6-2.3] versus 0.9 [0.4-1.5], P < 0.001, and exercise interruptions: 7.2 [5.9-8.8] versus 1.4 [0.8-2.1], P < 0.001, compared with control. There was no evidence of a difference in percentage time in range (3.9-10 mmol/L) and percentage time spent high between study arms. Both control and intervention protocols prevented significant hypoglycemia. Using a CHO intake algorithm based on CGM trends resulted in fewer CHO intake events and fewer interruptions to exercise. Use of this algorithm may reduce the burden of diabetes management with potential to facilitate activity in young people with T1D.
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Algoritmos , Automonitorização da Glicemia/métodos , Carboidratos/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico/fisiologia , Glicemia/análise , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , MasculinoRESUMO
OBJECTIVE: This study aimed to explore the effect of continuous glucose monitors with remote monitoring on psychosocial outcomes in parents of children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Children with type 1 diabetes, aged 2-12 years, along with their parents, were studied in a randomized crossover study. They participated in two 3-month periods using conventional blood glucose monitoring (control) or the Dexcom G5 Mobile continuous glucose monitoring (CGM) system with remote monitoring (intervention). The primary outcome was parental fear of hypoglycemia score assessed by the Hypoglycemia Fear Survey. RESULTS: Parental Hypoglycemia Fear Survey scores were lower while the child was using CGM with remote monitoring (P < 0.001). Furthermore, parental health-related quality of life and family functioning, stress, anxiety, and sleep measures also improved significantly after intervention. CONCLUSIONS: CGM with remote monitoring was found to improve multiple measures of quality of life, reduce family stress, and improve parental sleep.
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Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Pais/psicologia , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia , Criança , Pré-Escolar , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Medo/psicologia , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/psicologia , Masculino , Qualidade de Vida , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Long-term glycemic outcomes in people with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) with appropriate control data are limited. Randomized controlled studies of technology in diabetes care are generally limited in duration and likely to have a selection bias. Hence, evaluation of population-based data provides a robust alternative evaluation of the benefits of insulin pump therapy. AIM: To investigate the outcomes of insulin pump therapy, as compared to injection therapy, in children with T1D attending a state-wide diabetes service in Western Australia. METHODS: Patients using insulin pump therapy between January 1999 and July 2016 were matched to patients on injection therapy on the basis of age, date of diagnosis, and hemoglobin A1C (HbA1c) at the start of pump therapy. RESULTS: A total of 513 pump-injection matches were identified. The pump cohort had a significantly lower mean HbA1c for the first 6 years of follow-up. The difference in HbA1c between the cohorts was observed by 6 months (3 mmol/mol [0.3%], standard error of the mean (SEM) 0.05, N = 463 matched pairs, P < 0.001) and was sustained with the greatest difference in HbA1c at 6 years (4 mmol/mol [0.4%], SEM 0.21, N = 112 matched pairs, P = 0.04). Beyond 6 years of follow-up, the HbA1c was not significantly lower in the pump cohort (N < 70 matched pairs). CONCLUSIONS: Patients using insulin pump therapy had a better long-term glycemic control relative to the matched injection therapy cohort. Large population-based cohort studies using real-world data provide a valuable perspective on evaluation of new technologies in children with T1D.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Fatores Etários , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Lactente , Injeções Subcutâneas , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV) contribute to a much greater proportion of symptomatic cCMV than was previously thought. Here, we describe a case of symptomatic cCMV infection in the newborn of a woman with proven immunity prior to pregnancy. Diagnosis was confirmed by CMV PCR from amniotic fluid and fetal MR imaging. The newborn presented with typical cCMV symptoms including jaundice, hepatosplenomegaly, cholestasis, petechiae, small head circumference, and sensorineural hearing loss, the most common neurologic sequela. CMV was detected in infant blood and urine by PCR, and intravenous ganciclovir was initiated and continued orally for 6 weeks totally. Apart from persisting right-sided deafness, the child exhibited normal neurological development up through the last follow-up at 4.5 years. To date, the most effective strategy to prevent vertical CMV transmission is hygiene counseling for women of childbearing age, which, in our case, and in concordance with recent literature, applies to seronegative, as well as seropositive, women. Once an expecting mother shows seroconversion or signs of an active CMV infection, there are no established procedures to reduce the risk of transmission, or therapeutic options for the fetus with signs of infection. After birth, symptomatic infants can be treated with ganciclovir to inhibit viral replication and improve hearing ability and neurodevelopmental outcome. A comprehensive review of the literature, including our case study, reveals the most current and significant diagnostic and treatment options available. In conclusion, the triad of maternal hygiene counseling, postnatal hearing screening of all newborns, followed by CMV PCR in symptomatic infants, and antiviral therapy of infants with symptomatic cCMV provides an outline of best practice to reduce the burden of CMV transmission sequelae.
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CONTEXT: 3ß-hydroxysteroid dehydrogenase deficiency (3ßHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3ßHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. OBJECTIVE: To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. METHODS: Biochemical, genetic and immunohistochemical investigations on human biomaterials. RESULTS: A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. CONCLUSIONS: The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.
Assuntos
Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/patologia , Infertilidade Masculina/genética , Puberdade/genética , Testículo/patologia , Humanos , Recém-Nascido , Masculino , MutaçãoRESUMO
BACKGROUND AND AIM: Infection with Bordetella pertussis is most severe in young infants who frequently acquire it from adults. Pertussis immunization in adults 25-29 years of age and all adults in close contact with infants <6 months was introduced in Switzerland in 2012. We immediately implemented this new recommendation in our hospital with a vaccination campaign. METHODS: Between April 2012 and March 2013 we provided information about the campaign to our staff through several channels and offered appointments for counseling and immunization. After checking indications and contraindications of responding health-care personnel (HCP), informed consent for tetanus-diphtheria-acellular pertussis component (Tdap) immunization was obtained. Specific adverse events (AE) were self-assessed by standardized diaries for 7 days. Statistical analyses were performed using a t-test and Mann-Whitney U-tests SPSS (V21). RESULTS: Of 852 HCP eligible for pertussis immunization, 427 (51%) responded. Of these, 72 (17%) had already received Tdap <10 years ago, 304 (71%) received Tdap now, 38 (9%) were scheduled for vaccination and 12 (3%) declined. Diaries were returned by 272 (89%) of 304 vaccinees; 56 HCP reported ≥1 local AE, most frequently local swelling (8%), redness (2%), redness and swelling (7%), and fever (5=2%); no serious AE occurred. CONCLUSIONS: Comprehensive efforts were needed to achieve pertussis immunization coverage of ≥49% among all HCP in our institution. Good tolerability of the vaccine and continuous and individual information to HCP about the rationale and benefits of pertussis immunization contributed to this partial success, but increased efforts are needed to mobilize non-responding HCP.
Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Pessoal de Saúde , Programas de Imunização , Vacinação/estatística & dados numéricos , Coqueluche/prevenção & controle , Adulto , Difteria/prevenção & controle , Feminino , Pessoal de Saúde/educação , Humanos , Esquemas de Imunização , Lactente , Masculino , Suíça , Tétano/prevenção & controle , Vacinação/efeitos adversosRESUMO
BACKGROUND: Aromatase deficiency may result in a complete block of estrogen synthesis because of the failure to convert androgens to estrogens. In females, this results in virilisation at birth, ovarian cysts in prepuberty and lack of pubertal development but virilisation, thereafter. OBJECTIVE AND METHODS: We studied the impact of oral 17ß-estradiol treatment on ovarian and uterine development, and on LH/FSH and inhibin B during the long-term follow-up of a girl harboring compound heterozygote point mutations in the CYP19A1 gene. RESULTS: In early childhood, low doses of oral 17ß-estradiol were needed. During prepuberty treatment with slowly increasing doses of E2 resulted in normal uterine and almost normal development of ovarian volume, as well as number and size of follicles. Regarding hormonal feedback mechanisms, inhibin B levels were in the upper normal range during childhood and puberty. Low doses of estradiol did not suffice to achieve physiological gonadotropin levels in late prepuberty and puberty. However, when estradiol doses were further increased in late puberty levels of both FSH and LH declined with estradiol levels within normal range. CONCLUSION: Complete aromatase deficiency provides an excellent model of how ovarian and uterine development in relation to E2, LH, FSH and inhibin B feedback progresses from infancy to adolescence.