First Accuracy and User-Experience Evaluation of New Continuous Glucose Monitoring System for Hypoglycemia Due to Hyperinsulinism.

INTRODUCTION: Patients with congenital hyperinsulinism (HI) require constant glucose monitoring to detect and treat recurrent and severe hypoglycemia. Historically, this has been achieved with intermittent self-monitoring blood glucose (SMBG), but patients are increasingly using continuous glucose monitoring (CGM). Given the rapidity of CGM device development, and increasing calls for CGM use from HI families, it is vital that new devices are evaluated early. METHODS: We provided two months of supplies for the new Dexcom G7 CGM device to 10 patients with HI who had recently finished using the Dexcom G6. Self-monitoring blood glucose was performed concurrently with paired readings providing accuracy calculations. Patients and families completed questionnaires about device use at the end of the two-month study period. RESULTS: Compared to the G6, the G7 showed a significant reduction in mean absolute relative difference (25%-18%, P < .001) and in the over-read error (Bland Altman +1.96 SD; 3.54 mmol/L to 2.95 mmol/L). This resulted in an improvement in hypoglycemia detection from 42% to 62% (P < .001). Families reported an overall preference for the G7 but highlighted concerns about high sensor failure rates. DISCUSSION: The reduction in mean absolute relative difference and over-read error and the improvement in hypoglycemia detection implies that the G7 is a safer and more useful device in the management of hypoglycemia for patients with HI. Accuracy, while improved from previous devices, remains suboptimal with 40% of hypoglycemia episodes not detected.

Brain magnetic resonance imaging review suggests unrecognised hypoglycaemia in childhood.

Introduction: Neonatal and early-life hypoglycaemia, is a frequent finding but is often non-specific and asymptomatic, making detection and diagnosis challenging. Hypoglycaemia-induced cerebral injury can be identified by magnetic resonance imaging (MRI) changes in cerebral white matter, occipital lobes, and posterior parietotemporal regions. It is unknown if children may have hypoglycaemic brain injury secondary to unrecognised hypoglycaemia in early life. We have examined retrospective radiological findings of likely brain injury by neuroimaging to investigate the existence of previous missed hypoglycaemic events. Methods: Retrospective MRI data in children in a single tertiary centre, over a ten-year period was reviewed to identify potential cases of unrecognised early-life hypoglycaemia. A detailed search from an electronic radiology repository involved the term "hypoglycaemia'' from text-based reports. The initial report was used for those who required serial scanning. Images specific to relevant reports were further reviewed by a designated paediatric neuroradiologist to confirm likely hypoglycaemia induced brain injury. Medical records of those children were subsequently reviewed to assess if the hypoglycaemia had been diagnosed prior to imaging. Results: A total of 107 MR imaging reports were identified for review, and 52 (48.5%) showed typical features strongly suggestive of hypoglycaemic brain injury. Medical note review confirmed no documented clinical information of hypoglycaemia prior to imaging in 22 (42%) patients, raising the likelihood of missed hypoglycaemic events resulting in brain injury. Conclusions: We have identified the existence of unrecognised childhood hypoglycaemia through neuroimaging review. This study highlights the need for heightened awareness of early life hypoglycaemia to prevent adverse neurological outcomes later in childhood.

Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.

The behaviour change behind a successful pilot of hypoglycaemia reduction with HYPO-CHEAT.

Background: Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention vary from fingerprick glucose testing to the provision of continuous glucose monitoring (CGM) to machine learning (ML) driven glucose forecasting. Recent trends for ML have had limited success in preventing free-living hypoglycaemia, due to a focus on increasingly accurate glucose forecasts and a failure to acknowledge the human in the loop and the essential step of changing behaviour. The wealth of evidence from the fields of behaviour change and persuasive technology (PT) allows for the creation of a theory-informed and technologically considered approach. Objectives: We aimed to create a PT that would overcome the identified barriers to hypoglycaemia prevention for those with CHI to focus on proactive prevention rather than commonly used reactive approaches. Methods: We used the behaviour change technique taxonomy and persuasive systems design models to create HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-Cgm-HEatmap-Assisted-Technology): a novel approach that presents aggregated CGM data in simple visualisations. The resultant ease of data interpretation is intended to facilitate behaviour change and subsequently reduce hypoglycaemia. Results: HYPO-CHEAT was piloted in 10 patients with CHI over 12 weeks and successfully identified weekly patterns of hypoglycaemia. These patterns consistently correlated with identifiable behaviours and were translated into both a change in proximal fingerprick behaviour and ultimately, a significant reduction in aggregated hypoglycaemia from 7.1% to 5.4% with four out of five patients showing clinically meaningful reductions in hypoglycaemia. Conclusions: We have provided pilot data of a new approach to hypoglycaemia prevention that focuses on proactive prevention and behaviour change. This approach is personalised for individual patients with CHI and is a first step in changing our approach to hypoglycaemia prevention in this group.

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people.

Continuous glucose monitoring for children with hypoglycaemia: Evidence in 2023.

In 2023, childhood hypoglycaemia remains a major public health problem and significant risk factor for consequent adverse neurodevelopment. Irrespective of the underlying cause, key elements of clinical management include the detection, prediction and prevention of episodes of hypoglycaemia. These tasks are increasingly served by Continuous Glucose Monitoring (CGM) devices that measure subcutaneous glucose at near-continuous frequency. While the use of CGM in type 1 diabetes is well established, the evidence for widespread use in rare hypoglycaemia disorders is less than convincing. However, in the few years since our last review there have been multiple developments and increased user feedback, requiring a review of clinical application. Despite advances in device technology, point accuracy of CGM remains low for children with non-diabetes hypoglycaemia. Simple provision of CGM devices has not replicated the efficacy seen in those with diabetes and is yet to show benefit. Machine learning techniques for hypoglycaemia prevention have so far failed to demonstrate sufficient prediction accuracy for real world use even in those with diabetes. Furthermore, access to CGM globally is restricted by costs kept high by the commercially-driven speed of technical innovation. Nonetheless, the ability of CGM to digitally phenotype disease groups has led to a better understanding of natural history of disease, facilitated diagnoses and informed changes in clinical management. Large CGM datasets have prompted re-evaluation of hypoglycaemia incidence and facilitated improved trial design. Importantly, an individualised approach and focus on the behavioural determinants of hypoglycaemia has led to real world reduction in hypoglycaemia. In this state of the art review, we critically analyse the updated evidence for use of CGM in non-diabetic childhood hypoglycaemia disorders since 2020 and provide suggestions for qualified use.

The hypoglycaemia error grid: A UK-wide consensus on CGM accuracy assessment in hyperinsulinism.

Objective: Continuous Glucose Monitoring (CGM) is gaining in popularity for patients with paediatric hypoglycaemia disorders such as Congenital Hyperinsulinism (CHI), but no standard measures of accuracy or associated clinical risk are available. The small number of prior assessments of CGM accuracy in CHI have thus been incomplete. We aimed to develop a novel Hypoglycaemia Error Grid (HEG) for CGM assessment for those with CHI based on expert consensus opinion applied to a large paired (CGM/blood glucose) dataset. Design and methods: Paediatric endocrinology consultants regularly managing CHI in the two UK centres of excellence were asked to complete a questionnaire regarding glucose cutoffs and associated anticipated risks of CGM errors in a hypothetical model. Collated information was utilised to mathematically generate the HEG which was then approved by expert, consensus opinion. Ten patients with CHI underwent 12 weeks of monitoring with a Dexcom G6 CGM and self-monitored blood glucose (SMBG) with a Contour Next One glucometer to test application of the HEG and provide an assessment of accuracy for those with CHI. Results: CGM performance was suboptimal, based on 1441 paired values of CGM and SMBG showing Mean Absolute Relative Difference (MARD) of 19.3% and hypoglycaemia (glucose <3.5mmol/L (63mg/dL)) sensitivity of only 45%. The HEG provided clinical context to CGM errors with 15% classified as moderate risk by expert consensus when data was restricted to that of practical use. This provides a contrasting risk profile from existing diabetes error grids, reinforcing its utility in the clinical assessment of CGM accuracy in hypoglycaemia. Conclusions: The Hypoglycaemia Error Grid, based on UK expert consensus opinion has demonstrated inadequate accuracy of CGM to recommend as a standalone tool for routine clinical use. However, suboptimal accuracy of CGM relative to SMBG does not detract from alternative uses of CGM in this patient group, such as use as a digital phenotyping tool. The HEG is freely available on GitHub for use by other researchers to assess accuracy in their patient populations and validate these findings.

HYPO-CHEAT's aggregated weekly visualisations of risk reduce real world hypoglycaemia.

Background: Children with congenital hyperinsulinism (CHI) are at constant risk of hypoglycaemia with the attendant risk of brain injury. Current hypoglycaemia prevention methods centre on the prediction of a continuous glucose variable using machine learning (ML) processing of continuous glucose monitoring (CGM). This approach ignores repetitive and predictable behavioural factors and is dependent upon ongoing CGM. Thus, there has been very limited success in reducing real-world hypoglycaemia with a ML approach in any condition. Objectives: We describe the development of HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-CGM-HEatmap-Technology), which is designed to overcome these limitations by describing weekly hypoglycaemia risk. We tested HYPO-CHEAT in a real-world setting to evaluate change in hypoglycaemia. Methods: HYPO-CHEAT aggregates individual CGM data to identify weekly hypoglycaemia patterns. These are visualised via a hypoglycaemia heatmap along with actionable interpretations and targets. The algorithm is iterative and reacts to anticipated changing patterns of hypoglycaemia. HYPO-CHEAT was compared with Dexcom Clarity's pattern identification and Facebook Prophet's forecasting algorithm using data from 10 children with CHI using CGM for 12 weeks. HYPO-CHEAT's efficacy was assessed via change in time below range (TBR). Results: HYPO-CHEAT identified hypoglycaemia patterns in all patients. Dexcom Clarity identified no patterns. Predictions from Facebook Prophet were inconsistent and difficult to interpret. Importantly, the patterns identified by HYPO-CHEAT matched the lived experience of all patients, generating new and actionable understanding of the cause of hypos. This facilitated patients to significantly reduce their time in hypoglycaemia from 7.1% to 5.4% even when real-time CGM data was removed. Conclusions: HYPO-CHEAT's personalised hypoglycaemia heatmaps reduced total and targeted TBR even when CGM was reblinded. HYPO-CHEAT offers a highly effective and immediately available personalised approach to prevent hypoglycaemia and empower patients to self-care.

Families' Experiences of Continuous Glucose Monitoring in the Management of Congenital Hyperinsulinism: A Thematic Analysis.

Background and Aims: In patients with congenital hyperinsulinism (CHI), recurrent hypoglycaemia can lead to longstanding neurological impairments. At present, glycaemic monitoring is with intermittent fingerprick blood glucose testing but this lacks utility to identify patterns and misses hypoglycaemic episodes between tests. Although continuous glucose monitoring (CGM) is well established in type 1 diabetes, its use has only been described in small studies in patients with CHI. In such studies, medical perspectives have been provided without fully considering the views of families using CGM. In this qualitative study, we aimed to explore families' experiences of using CGM in order to inform future clinical strategies for the management of CHI. Methods: Ten patients with CHI in a specialist centre used CGM for twelve weeks. All were invited to participate. Semi-structured interviews were conducted with nine families in whom patient ages ranged between two and seventeen years. Transcripts of the audio-recorded interviews were analysed using an inductive thematic analysis method. Results: Analysis revealed five core themes: CGM's function as an educational tool; behavioural changes; positive experiences; negative experiences; and design improvements. Close monitoring and retrospective analysis of glucose trends allowed for enhanced understanding of factors that influenced glucose levels at various times of the day. Parents noted more hypoglycaemic episodes than previously encountered through fingerprick tests; this new knowledge prompted modification of daily routines to prevent and improve the management of hypoglycaemia. CGM use was viewed favourably as offering parental reassurance, reduced fingerprick tests and predictive warnings. However, families also reported unfavourable aspects of alarms and questionable accuracy at low glucose levels. Adolescents were frustrated by the short proximity range for data transmission resulting in the need to always carry a separate receiver. Overall, families were positive about the use of CGM but expected application to be tailored to their child's medical condition. Conclusions: Patients and families with CHI using CGM noticed trends in glucose levels which motivated behavioural changes to reduce hypoglycaemia with advantages outweighing disadvantages. They expected CHI-specific modifications to enhance utility. Future design of CGM should incorporate end users' opinions and experiences for optimal glycaemic monitoring of CHI.

Insight into hypoglycemia frequency in congenital hyperinsulinism: evaluation of a large UK CGM dataset.

INTRODUCTION: Hypoglycemia is often recurrent and severe in patients with congenital hyperinsulinism (CHI). However, there is little information regarding frequency or patterns of episodes to inform clinical management and future trial design. RESEARCH DESIGN AND METHODS: We aimed to describe frequency and patterns of hypoglycemia by varying thresholds through a large continuous glucose monitoring (CGM) dataset. Through the UK CHI centers of excellence, data were analyzed from patients with CHI over a 5-year period. Hypoglycemia thresholds of 3.0 (H3.0), 3.5 (H3.5) and 3.9 (H3.9) mmol/L were used to test threshold change on hypoglycemia frequencies. RESULTS: From 63 patients, 3.4 million data points, representing 32 years of monitoring, were analyzed. By UK consensus threshold H3.5, patients experienced a mean 1.3 hypoglycemic episodes per day. Per cent time hypoglycemic increased from 1.2% to 3.3% to 6.9% when threshold changed from H3.0 to H3.5 and H3.9. Merged data showed periodicity of hypoglycemia risk in 24-hour periods in all patients. CONCLUSIONS: We have evaluated a large dataset to provide a comprehensive picture of the frequency and patterns of hypoglycemia for patients with CHI in the UK. These data establish a baseline risk of hypoglycemia by CGM and provide a framework for clinical management and clinical trial design.