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BACKGROUND: Whether improved glucose control with hybrid closed-loop therapy can preserve C-peptide secretion as compared with standard insulin therapy in persons with new-onset type 1 diabetes is unclear. METHODS: In a multicenter, open-label, parallel-group, randomized trial, we assigned youths 10.0 to 16.9 years of age within 21 days after a diagnosis of type 1 diabetes to receive hybrid closed-loop therapy or standard insulin therapy (control) for 24 months. The primary end point was the area under the curve (AUC) for the plasma C-peptide level (after a mixed-meal tolerance test) at 12 months after diagnosis. The analysis was performed on an intention-to-treat basis. RESULTS: A total of 97 participants (mean [±SD] age, 12±2 years) underwent randomization: 51 were assigned to receive closed-loop therapy and 46 to receive control therapy. The AUC for the C-peptide level at 12 months (primary end point) did not differ significantly between the two groups (geometric mean, 0.35 pmol per milliliter [interquartile range, 0.16 to 0.49] with closed-loop therapy and 0.46 pmol per milliliter [interquartile range, 0.22 to 0.69] with control therapy; mean adjusted difference, -0.06 pmol per milliliter [95% confidence interval {CI}, -0.14 to 0.03]). There was not a substantial between-group difference in the AUC for the C-peptide level at 24 months (geometric mean, 0.18 pmol per milliliter [interquartile range, 0.06 to 0.22] with closed-loop therapy and 0.24 pmol per milliliter [interquartile range, 0.05 to 0.30] with control therapy; mean adjusted difference, -0.04 pmol per milliliter [95% CI, -0.14 to 0.06]). The arithmetic mean glycated hemoglobin level was lower in the closed-loop group than in the control group by 4 mmol per mole (0.4 percentage points; 95% CI, 0 to 8 mmol per mole [0.0 to 0.7 percentage points]) at 12 months and by 11 mmol per mole (1.0 percentage points; 95% CI, 7 to 15 mmol per mole [0.5 to 1.5 percentage points]) at 24 months. Five cases of severe hypoglycemia occurred in the closed-loop group (in 3 participants), and one occurred in the control group; one case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In youths with new-onset type 1 diabetes, intensive glucose control for 24 months did not appear to prevent the decline in residual C-peptide secretion. (Funded by the National Institute for Health and Care Research and others; CLOuD ClinicalTrials.gov number, NCT02871089.).
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Peptídeo C , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Insulina , Adolescente , Glicemia/análise , Peptídeo C/metabolismo , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Sistemas de Infusão de InsulinaRESUMO
BACKGROUND: GNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein-coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright's hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism). METHODS: We performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays. RESULTS: Almost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone-releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, -0.90 vs. 0.75, respectively; P = 0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P = 0.004). CONCLUSIONS: Because pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.).
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Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação , Obesidade Infantil/genética , Receptor Tipo 4 de Melanocortina/metabolismo , Adolescente , Estatura , Criança , Cromograninas/genética , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/deficiência , Humanos , Masculino , Mutação de Sentido Incorreto , Receptores da Tireotropina/metabolismo , Transdução de Sinais , Sequenciamento do ExomaRESUMO
Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialised algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months post-initiation on glycated haemoglobin (HbA1c), time-in-range (TIR), hypoglycaemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight paediatric diabetes centres across England under the National Health Service England's (NHSE) HCL pilot real-world study. A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilised three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM.All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycaemia frequency (50% reduction), hypoglycaemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycaemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycaemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them.
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Glicemia , Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Insulina , Qualidade de Vida , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Masculino , Criança , Adolescente , Feminino , Glicemia/efeitos dos fármacos , Insulina/administração & dosagem , Insulina/uso terapêutico , Inglaterra , Automonitorização da Glicemia/métodos , Hemoglobinas Glicadas/análise , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Estudos Prospectivos , Hipoglicemia , Controle Glicêmico/métodosRESUMO
AIMS: Hybrid closed-loop (HCL) systems are characterised by integrating continuous glucose monitoring (CGM) with insulin pumps that automate insulin delivery via specific algorithms and user-initiated insulin delivery. The aim of the study was to evaluate effectiveness of HCLs on HbA1c, time-in-range (TIR), hypoglycaemia frequency and quality of life measures in children and young people (CYP) with T1D, and their carers. METHODS: Patients were recruited prospectively into the National Health Service (NHS) England real-world HCL observational study from the 1st of August 2021 to the 10th of December 2022 from eight paediatric diabetes centres in England. RESULTS: There were 251 CYP (147 males, 58%) with T1DM recruited with a mean age at recruitment of 12.3 (SD 3.5) (range 2-19) years. Eighty nine per cent of the CYP were of white ethnicity, 3% Asian, 4% black and 3% mixed ethnicity, and 1% were recorded as others. The HCL systems used in the study were: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA) with the Dexcom G6® CGM (Dexcom, San Diego, CA) sensor; (2) Medtronic MiniMed™ 780G (Medtronic, Northridge, CA) and (3) CamAPS FX (CamDiab, Cambridge, UK.) All systems were fully funded by the national health service. CONCLUSIONS: The results of the NHS England Closed Loop Study in Children and Young People showed improvements in glycaemic control, TIR, frequency of hypoglycaemia, hypoglycaemia fear and quality of sleep for children and young people when using HCL for 6 months. Hypoglycaemia fear and quality of sleep were also improved for their parents and carers at 6 months.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Masculino , Humanos , Criança , Adolescente , Pré-Escolar , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Medicina Estatal , Glicemia , Qualidade de Vida , Automonitorização da Glicemia/métodos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Insulina/uso terapêutico , Inglaterra/epidemiologia , Sistemas de Infusão de Insulina , Hipoglicemiantes/uso terapêuticoRESUMO
The National Institute for Clinical Excellence updated guidance for continuous glucose monitoring (CGM) in 2022, recommending that CGM be available to all people living with type 1 diabetes. Manufacturers can trade in the UK with Conformité Européenne (CE) marking without an initial national assessment. The regulatory process for CGM CE marking, in contrast to the Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) process, is described. Manufacturers operating in the UK provided clinical accuracy studies submitted for CE marking. Critical appraisal of the studies shows several CGM devices have CE marking for wide-ranging indications beyond available data, unlike FDA and TGA approval. The FDA and TGA use tighter controls, requiring comprehensive product-specific clinical data evaluation. In 2018, the FDA published the integrated CGM (iCGM) criteria permitting interoperability. Applying the iCGM criteria to clinical data provided by manufacturers trading in the UK identified several study protocols that minimized glucose variability, thereby improving CGM accuracy on all metrics. These results do not translate into real-life performance. Furthermore, for many CGM devices available in the UK, accuracy reported in the hypoglycaemic range is below iCGM standards, or measurement is absent. We offer a framework to evaluate CGM accuracy studies critically. The review concludes that FDA- and TGA-approved indications match the available clinical data, whereas CE marking indications can have discrepancies. The UK can bolster regulation with UK Conformity Assessed marking from January 2025. However, balanced regulation is needed to ensure innovation and timely technological access are not hindered.
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Glicemia , Diabetes Mellitus Tipo 1 , Estados Unidos , Humanos , Automonitorização da Glicemia , United States Food and Drug Administration , Austrália , Diabetes Mellitus Tipo 1/tratamento farmacológicoRESUMO
BACKGROUND: Brown adipose tissue (BAT) is essential to maintain body temperature. Its ability to convert chemical energy in glucose and free fatty acids to heat is conferred by a unique protein, UCP-1. BAT activity is greatest in children and adolescents, declining through adulthood. Blood glucose concentrations outside the normal nondiabetic range are common in type 1 diabetes and hyperglycaemia leads to insulin resistance in muscle and white adipose tissue, but whether this applies to BAT, is not known. METHOD: To investigate the effect of type 1 diabetes on BAT activity, we measured the supraclavicular temperature of 20 children with type 1 diabetes and compared them to 20 age-matched controls, using infrared thermography. RESULTS: The diabetes group had lower stimulated supraclavicular temperatures (diabetes group: 35.03 (34.76-35.30)°C; control group: 35.42 (35.16-35.69)°C; p = 0.037) and a reduced response in relative temperature following cold stimulation, after adjusting for BMI (diabetes group: 0.11 (0.03-0.18)°C; control group: 0.22 (0.15-0.29)°C; p = 0.034). In the diabetes group, there was no association between glycaemic measures and supraclavicular temperatures, but the method of insulin delivery may significantly affect the change in supraclavicular temperature with stimulation (injections: 0.01 (-0.07-0.09)°C; pump: 0.15 (0.04-0.26)°C; p = 0.028). CONCLUSIONS: While further work is needed to better understand the glucose-insulin-BAT relationship, one possible explanation for the reduced supraclavicular temperature is that exogenous, unlike endogenous, insulin, is not suppressed by the activity of the sympathetic nervous system, preventing lipolysis-driven activation of BAT.
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Tecido Adiposo Marrom/fisiopatologia , Temperatura Baixa , Diabetes Mellitus Tipo 1/fisiopatologia , Estimulação Física , Termogênese/fisiologia , Adolescente , Fatores Etários , Glicemia , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Masculino , Temperatura Cutânea , TermografiaRESUMO
BACKGROUND: The role of technology in the self-management of type 1 diabetes mellitus (T1DM) among children and young people is not well understood. Interventions should aim to improve key diabetes self-management behaviours (self-management of blood glucose, insulin administration, physical activity and dietary behaviours) and prerequisites (psychological outcomes and HbA1c) highlighted in the UK guidelines of the National Institute for Health and Care Excellence (NICE) for management of T1DM. The purpose was to identify evidence to assess the effectiveness of technological tools in promoting aspects of these guidelines amongst children and young people. METHODS: A systematic review of English language articles was conducted using the following databases: Web of Science, PubMed, Scopus, NUSearch, SAGE Journals, SpringerLink, Google Scholar, Science Direct, Sport Discus, Embase, Psychinfo and Cochrane Trials. Search terms included paediatric, type one diabetes, technology, intervention and various synonyms. Included studies examined interventions which supplemented usual care with a health care strategy primarily delivered through a technology-based medium (e.g. mobile phone, website, activity monitor) with the aim of engaging children and young people with T1DM directly in their diabetes healthcare. Studies did not need to include a comparator condition and could be randomised, non-randomised or cohort studies but not single-case studies. RESULTS: Of 30 included studies (21 RCTs), the majority measured self-monitoring of blood glucose monitoring (SMBG) frequency, clinical indicators of diabetes self-management (e.g. HbA1c) and/or psychological or cognitive outcomes. The most positive findings were associated with technology-based health interventions targeting SMBG as a behavioural outcome, with some benefits found for clinical and/or psychological diabetes self-management outcomes. Technological interventions were well accepted by children and young people. For the majority of included outcomes, clinical relevance was deemed to be little or none. CONCLUSIONS: More research is required to assess which elements of interventions are most likely to produce beneficial behavioural outcomes. To produce clinically relevant outcomes, interventions may need to be delivered for at least 1 year and should consider targeting individuals with poorly managed diabetes. It is not possible to determine the impact of technology-based interventions on insulin administration, dietary habits and/or physical activity behaviour due to lack of evidence.
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Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/terapia , Monitorização Fisiológica/instrumentação , Autogestão/métodos , Adolescente , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Comportamentos Relacionados com a Saúde , Humanos , Insulina/uso terapêutico , Aplicativos Móveis , Monitorização Fisiológica/métodos , Comportamento de Redução do Risco , Interface Usuário-Computador , Dispositivos Eletrônicos VestíveisRESUMO
BACKGROUND: Physical activity and self-monitoring are important for children with type 1 diabetes mellitus (T1DM) but it is unclear whether interventions delivered online are feasible, acceptable to patients and efficacious. The aim was to assess the feasibility and acceptability of an internet-based physical activity and self-monitoring programme for children with T1DM, and of a randomised controlled trial (RCT) to evaluate efficacy. METHODS: A total of 49 children aged 9-12 with T1DM were randomly assigned to usual care only or to an interactive intervention group combining a website (STAK-D) and a PolarActive activity watch (PAW; Polar Electro (UK) Ltd.), alongside usual care. Participants completed self-report measures on their health, self-efficacy and physical activity at baseline (T0), eight weeks (T1) and six months (T2). They also wore a PAW to measure physical activity for one week at the end of T0, T1 and T2. Intervention participants were interviewed about their experiences at T2. Explanatory variables were examined using multi-level modelling and examination of change scores, 95% confidence intervals and p-values with alpha set at 0.95. Descriptive analysis was undertaken of the 'end-of-study questionnaire'. Qualitative analysis followed a framework approach. RESULTS: Completion rates for all self-report items and objective physical activity data were above 85% for the majority of measures. HbA1c data was obtained for 100% of participants, although complete clinical data was available for 63.3% to 63.5% of participants at each data collection time-point. Recruitment and data collection processes were reported to be acceptable to participants and healthcare professionals. Self-reported sedentary behaviour (-2.28, p=0.04, 95% CI=-4.40, -0.16; p = 0.04; dppc2 = 0.72) and parent-reported physical health of the child (6.15, p=0.01, 95%CI=1.75, 10.55; p = 0.01; dppc2 = 0.75) improved at eight weeks in the intervention group. CONCLUSIONS: The trial design was feasible and acceptable to participants and healthcare providers. Intervention engagement was low and technical challenges were evident in both online and activity watch elements, although enjoyment was high among users. Reported outcome improvements were observed at 8 weeks but were not sustained. TRIAL REGISTRATION: ISRCTN 48994721 (prospectively registered). Date of registration: 28.09.2016.
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Diabetes Mellitus Tipo 1 , Exercício Físico , Internet , Satisfação do Paciente , Avaliação de Programas e Projetos de Saúde , Atitude do Pessoal de Saúde , Criança , Diabetes Mellitus Tipo 1/terapia , Estudos de Viabilidade , Feminino , Pessoal de Saúde , Nível de Saúde , Humanos , Masculino , Monitorização Ambulatorial , Comportamento Sedentário , Autoeficácia , Inquéritos e QuestionáriosRESUMO
The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.
Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Humanos , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/etiologia , Glicemia , Sistemas de Infusão de Insulina , Insulina Regular HumanaRESUMO
OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. RESEARCH DESIGN AND METHODS: Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference -2 [95% CI -7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion.
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Glicemia , Peptídeo C , Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Adolescente , Peptídeo C/sangue , Insulina/uso terapêutico , Insulina/administração & dosagem , Masculino , Criança , Feminino , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hemoglobinas Glicadas/metabolismoRESUMO
INTRODUCTION: Quantifying differences in service provision for children and young people (CYP) living with Congenital Adrenal Hyperplasia (CAH) across the United Kingdom. METHODS: A national service evaluation using online questionnaires circulated to patients and clinicians from secondary and tertiary UK centres managing CYP with CAH, and via the "Living with CAH" support group mailing list. RESULTS: Total of 195 responses relating to patients aged 0-20 years attending 33 clinics (43 patients, 152 carers), as well as 34 clinicians from 18 trusts working across the 33 clinics. Only 12% of clinicians were 'completely satisfied' with the service provided, compared to 68% of carers and 76% of patients. Whilst 94% of clinicians reported providing formal training to families with CAH, over 80% of both patients and carers reported not attending what they considered formal training. Appetite for further training was higher in carers (86%) than patients (55%), although further 'unsure' responses suggested formal training sessions would likely be well attended. Access to psychological services was difficult for 44% of clinicians. Biochemical monitoring of treatment was broadly in keeping with international guidelines, with 67% of clinicians reporting regular use of dried blood spots, and 12% regular urinary steroid metabolites. CONCLUSION: While there is overall good satisfaction with care provision among patients and carers with CAH in the UK, extra resources addressing the psychological and educational needs about the disease and its management would benefit patients and carers. Improved access to allied health professionals and psychologists will help support families and improve patient outcomes.
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Context: Recurrent hypoglycemia can result in significant neurological impairments in children and continuous glucose monitoring (CGM) technology has been shown to reduce recurrent hypoglycemia in conditions such as type 1 diabetes. In the United Kingdom, CGM devices are currently only recommended by the National Institute of Clinical Excellence (NICE) for patients with diabetes and not for other diagnoses. Objective: To examine access to CGM technology for children and young people with recurrent hypoglycemia in the United Kingdom. Methods: In 2021, the British Society of Paediatric Endocrinology and Diabetes (BSPED) conducted a national health professional survey in England, Wales, Scotland, and Northern Ireland looking at CGM access to funding for children and young people with recurrent hypoglycemia, without the diagnosis of diabetes. The UK Children's Hyperinsulinism Charity (UK CHC) also conducted a national patient survey. Results: Responses from BSPED were received from 55 units while the UK CHC received 69 responses from individual families, the largest response to a survey carried out by the charity. The results of the BSPED and UK CHC surveys found that funding streams for CGM were highly variable. Only 29% were able to access CGM for recurrent hypoglycemia and from these, 65% were self-funding CGM. Quality of life benefits were evident from the UK CHC survey on the utility of CGM in reducing worry, improving sleep, lessening the burden of frequently finger-pricking and reducing out-of-hours appointments as a result of hypoglycemia. Patient-reported utilization rates of blood glucose test strips per week were significantly reduced. Conclusion: BSPED and UK CHC national surveys support a call and a consideration for CGM access to be widened to patients who suffer from recurrent hypoglycemia such as those with hyperinsulinism or metabolic conditions. The prevention of recurrent hypoglycemia and improving quality of life for patients and carers remain a cornerstone management for people who suffer from frequent hypoglycemia. CGM education is critical to support its use and understand its limitations. Further research is warranted to determine the safety and efficacy of CGM in detection and reduction of hypoglycemic events, impact of hospital stay, and long-term neurological outcomes in those who suffer from recurrent hypoglceamia.
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CONTEXT: Quality of life (QoL) has been inconsistently reported in children and young people (CYP) with congenital adrenal hyperplasia (CAH). OBJECTIVE: Assess QoL in CYP with CAH in the UK alongside biometric and androgen profiles. DESIGN: To define the evidence base for health care delivery, we conducted a cross-sectional study in CYP with CAH in the UK. Questionnaire results were compared with normative data and between groups, and modelled for association with sex, height, weight, body mass index, or steroid biomarkers of CAH control. SETTING: Tertiary care in 14 UK centers. PATIENTS: Results from 104 patients, 55% female, mean age 12.7 years (SD 3.0), paired responses from parents. INTERVENTIONS: Strengths and Difficulties questionnaire (SDQ) and pediatric QoL questionnaire. MAIN OUTCOME MEASURE: Total QoL scores as assessed by SDQ and a pediatric QoL questionnaire in comparison to normative data. RESULTS: Total scores were worse in parents than normative data, but similar in patients. Patient QoL was rated better in social functioning but worse in emotional, school, and peer domains by patients, and worse in total scores and domains of peer problems, and psychosocial, emotional, and school functioning by parents. Parents consistently scored QoL of their children lower than their child. Larger height-SD score and lower weight-SD score were associated with better QoL. Girls with lower steroid biomarkers had worse SDQ scores. CONCLUSIONS: In CYP with CAH, reduced height, increased weight, and hormonal biomarkers consistent with overtreatment were associated with worse QoL; addressing these problems should be prioritized in clinical management.Clinical Trials Registration Number: SCH/15/088.
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Hiperplasia Suprarrenal Congênita , Criança , Humanos , Feminino , Adolescente , Masculino , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Qualidade de Vida/psicologia , Estudos Transversais , Biomarcadores , Esteroides , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: In girls with adolescent idiopathic scoliosis (AIS) the finding of abnormal extra-spinal bilateral skeletal length asymmetries in upper limbs, periapical ribs, and ilia begs the question whether these bilateral asymmetries are connected in some way with pathogenesis. MATERIAL AND METHODS: We investigated upper arm length (UAL) asymmetries in two groups of right-handed girls aged 11-18 years with right thoracic adolescent idiopathic scoliosis (RT-AIS, n=95) from preoperative and screening referrals (mean Cobb angle 46°) and healthy controls (n=240). Right and left UAL were measured with a Harpenden anthropometer of the Holtain equipment, Asymmetry was calculated as UAL difference, right minus left, in mm. Repeatability of the measurements was assessed as technical error of the measurement and coefficient of reliability. RESULTS: In girls with RT-AIS, UAL asymmetry was greater than in healthy girls, regressed negatively with age and correlated significantly with Cobb angle and apical vertebral rotation. In healthy girls, UAL asymmetry was unrelated to age. Plotted against years after estimated menarcheal age, UAL asymmetry decreased significantly for girls with RT-AIS but not for healthy girls. DISCUSSION AND CONCLUSIONS: The apparent transience of the abnormal UAL asymmetry suggests it is not secondary to spinal deformity but pathogenetically associated with it. We suggest two hypotheses to account for these changes: (1) a transient asymmetry process with growth velocity; and (2) in the light of subsequent research, early skeletal overgrowth with catch-down growth affecting right but not left upper arm. The relation of the upper arm length asymmetry to the increased length of periapical left ribs reported for RT-AIS is unknown. Right upper arm length may provide a more simple model than arm span, for estimating linear skeletal overgrowth of girls with RT-AIS.
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Braço/fisiopatologia , Doenças do Desenvolvimento Ósseo/complicações , Doenças do Desenvolvimento Ósseo/fisiopatologia , Modelos Biológicos , Escoliose/complicações , Escoliose/fisiopatologia , Vértebras Torácicas/fisiopatologia , Adolescente , Braço/anormalidades , Doenças do Desenvolvimento Ósseo/diagnóstico , Criança , Feminino , Humanos , Reprodutibilidade dos Testes , Escoliose/diagnóstico , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
Type 1 diabetes (T1D) is a chronic autoimmune disease of childhood affecting 1:500 children aged under 15 years, with around 25% presenting with life-threatening diabetic ketoacidosis (DKA). While first-degree relatives have the highest risk of T1D, more than 85% of children who develop T1D do not have a family history. Despite public health awareness campaigns, DKA rates have not fallen over the last decade. T1D has a long prodrome, and it is now possible to identify children who go on to develop T1D with a high degree of certainty. The reasons for identifying children presymptomatically include prevention of DKA and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. Research studies of population-based screening strategies include using islet autoantibodies alone or in combination with genetic risk factors, both of which can be measured from a capillary sample. If found during screening, the presence of two or more islet autoantibodies has a high positive predictive value for future T1D in childhood (under 18 years), offering an opportunity for DKA prevention. However, a single time-point test will not identify all children who go on to develop T1D, and so combining with genetic risk factors for T1D may be an alternative approach. Here we discuss the pros and cons of T1D screening in the UK, the different strategies available, the knowledge gaps and why a T1D screening strategy is needed.
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Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Adolescente , Autoanticorpos , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Cetoacidose Diabética/diagnóstico , Humanos , Programas de Rastreamento , Reino Unido/epidemiologiaRESUMO
The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function. A number of aggrecan (ACAN) gene variants have been linked to skeletal disorders, ranging from short stature to severe chondrodyplasias. Osteochondritis dissecans is a disorder where articular cartilage and subchondral bone fragments come loose from the articular surface. We previously reported a missense ACAN variant linked to familial osteochondritis dissecans, with short stature and early onset osteoarthritis, and now describe three novel ACAN gene variants from additional families with this disorder. Like the previously described variant, these are autosomal dominant missense variants, resulting in single amino acid residue substitutions in the C-type lectin repeat of the aggrecan G3 domain. Functional studies showed that neither recombinant variant proteins, nor full-length variant aggrecan proteoglycan from heterozygous patient cartilage, were secreted to the same level as wild-type aggrecan. The variant proteins also showed decreased binding to known cartilage extracellular matrix ligands. Mapping these and other ACAN variants linked to hereditary skeletal disorders showed a clustering of osteochondritis dissecans-linked variants to the G3 domain. Taken together, this supports a link between missense ACAN variants affecting the aggrecan G3 domain and hereditary osteochondritis dissecans.
Assuntos
Nanismo , Osteocondrite Dissecante , Agrecanas/genética , Agrecanas/metabolismo , Nanismo/genética , Humanos , Mutação de Sentido Incorreto , Osteocondrite Dissecante/congênito , Osteocondrite Dissecante/genéticaRESUMO
Objective: There is limited knowledge on the onset of comorbidities in congenital adrenal hyperplasia (CAH) during childhood. We aimed to establish the health status of children with CAH in the UK. Design and methods: This cross-sectional multicentre study involved 14 tertiary endocrine UK units, recruiting 101 patients aged 8-18 years with classic 21-hydroxylase deficiency and 83 controls. We analysed demographic, clinical and metabolic data, as well as psychological questionnaires (Strengths and Difficulties (SDQ), Paediatric Quality of Life (PedsQL)). Results: Patient height SDS in relation to mid-parental height decreased with age, indicating the discrepancy between height achieved and genetic potential height. Bone age was advanced in 40.5% patients, with a mean difference from the chronological age of 1.8 (±2.3) years. Patients were more frequently overweight (27%) or obese (22%) compared to controls (10.8% and 10.8%, respectively, P < 0.001). No consistent relationship between glucocorticoid dose and anthropometric measurements or hormonal biomarkers was detected. A small number of patients had raised total cholesterol (3.0%), low HDL (3.0%), raised LDL (7.0%) and triglycerides (5.0%). SDQ scores were within the 'high' and 'very high' categories of concern for 16.3% of patients. 'School functioning' was the lowest PedsQL scoring dimension with a median (interquartile range) of 70 (55-80), followed by 'emotional functioning' with a median of 75 (65-85). Conclusions: Our results show an increased prevalence of problems with growth and weight gain in CAH children and suggest reduced quality of life. This highlights the urgent need to optimise management and monitoring strategies to improve long-term health outcomes.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/metabolismo , Biomarcadores , Criança , Colesterol , Estudos Transversais , Glucocorticoides , Nível de Saúde , Humanos , Qualidade de Vida , Triglicerídeos , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: Many hybrid closed-loop (HCL) systems struggle to manage unusually high glucose levels as experienced with intercurrent illness or pre-menstrually. Manual correction boluses may be needed, increasing hypoglycemia risk with overcorrection. The Cambridge HCL system includes a user-initiated algorithm intensification mode ("Boost"), activation of which increases automated insulin delivery by approximately 35%, while remaining glucose-responsive. In this analysis, we assessed the safety of "Boost" mode. METHODS: We retrospectively analyzed data from closed-loop studies involving young children (1-7 years, n = 24), children and adolescents (10-17 years, n = 19), adults (≥24 years, n = 13), and older adults (≥60 years, n = 20) with type 1 diabetes. Outcomes were calculated per participant for days with ≥30 minutes of "Boost" use versus days with no "Boost" use. Participants with <10 "Boost" days were excluded. The main outcome was time spent in hypoglycemia <70 and <54 mg/dL. RESULTS: Eight weeks of data for 76 participants were analyzed. There was no difference in time spent <70 and <54 mg/dL between "Boost" days and "non-Boost" days; mean difference: -0.10% (95% confidence interval [CI] -0.28 to 0.07; P = .249) time <70 mg/dL, and 0.03 (-0.04 to 0.09; P = .416) time < 54 mg/dL. Time in significant hyperglycemia >300 mg/dL was 1.39 percentage points (1.01 to 1.77; P < .001) higher on "Boost" days, with higher mean glucose and lower time in target range (P < .001). CONCLUSIONS: Use of an algorithm intensification mode in HCL therapy is safe across all age groups with type 1 diabetes. The higher time in hyperglycemia observed on "Boost" days suggests that users are more likely to use algorithm intensification on days with extreme hyperglycemic excursions.
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BACKGROUND: CamAPS FX is a hybrid closed-loop smartphone app used to manage type one diabetes. The closed-loop algorithm has a default target glucose of 5.8 mmol/L (104.5 mg/dL), but users can select personal glucose targets (adjustable between 4.4 mmol/L and 11.0 mmol/L [79 mg/dL and 198 mg/dL, respectively]). METHOD: In this post-hoc analysis, we evaluated the impact of personal glucose targets on glycemic control using data from participants in five randomized controlled trials. RESULTS: Personal glucose targets were widely used, with 20.3% of all days in the data set having a target outside the default target bin (5.5-6.0 mmol/L [99-108 mg/dL]). Personal glucose targets >6.5 mmol/L (117 mg/dL) were associated with significantly less time in target range (3.9-10.0 mmol/L [70-180 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: mean difference = -3.2 percentage points [95% CI: -5.3 to -1.2; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -10.8 percentage points [95% CI: -14.1 to -7.6; P < .001]). Personal targets >6.5 mmol/L (117 mg/dL) were associated with significantly lower time (<3.9 mmol/L [<70 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: -1.85 percentage points [95% CI: -2.37 to -1.34; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -2.68 percentage points [95% CI: -3.49 to -1.86; P < .001]). CONCLUSIONS: Discrete study populations showed differences in glucose control when applying similar personal targets.
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Objective: To understand and explore data sharing practices among adolescents and their parents using a closed-loop system. Methods: Eighteen adolescents (aged 11-18 years) and 19 parents were interviewed after adolescents had â¼6 months experience of using a closed-loop system, which permitted them to share glucose and insulin data with parents/caregivers. Data were analyzed thematically. Results: There was considerable variability in how parent-child dyads perceived, valued, and undertook data sharing. Parents of early adolescents (11-13 years) reported making extensive use of "real time" data to remotely manage their child's diabetes and early adolescents described needing and wanting this input. Parents of middle adolescents (14-16 years) described making greater use of retrospective data. To avoid conflict and encourage and support their son/daughter's autonomy, these individuals reported practicing watchful waiting and only intervening after concerns about a pattern of problematic behavior or their child's safety arose. Middle adolescents indicated that data sharing had been done primarily for the benefit of their parents, although they also noted quality of life benefits for themselves. Among late adolescents (17+ years), parents were simply remote because their son/daughter had not permitted access to their data. Participants recommended clear ground rules be put in place about when, and how, data sharing should be used. Conclusions: To help parent-child dyads use data sharing in ways which minimize conflict and optimize constructive parental support, we recommend tailored input and support, which takes account of family dynamics, the young person's developmental maturity, and the different ways in which data are used across the adolescent age range.