A narrative commentary about interoperability in medical devices and data used in diabetes therapy from an academic EU/UK/US perspective.

People living with diabetes have many medical devices available to assist with disease management. A critical aspect that must be considered is how systems for continuous glucose monitoring and insulin pumps communicate with each other and how the data generated by these devices can be downloaded, integrated, presented and used. Not only is interoperability associated with practical challenges, but also devices must adhere to all aspects of regulatory and legal frameworks. Key issues around interoperability in terms of data ownership, privacy and the limitations of interoperability include where the responsibility/liability for device and data interoperability lies and the need for standard data-sharing protocols to allow the seamless integration of data from different sources. There is a need for standardised protocols for the open and transparent handling of data and secure integration of data into electronic health records. Here, we discuss the current status of interoperability in medical devices and data used in diabetes therapy, as well as regulatory and legal issues surrounding both device and data interoperability, focusing on Europe (including the UK) and the USA. We also discuss a potential future landscape in which a clear and transparent framework for interoperability and data handling also fulfils the needs of people living with diabetes and healthcare professionals.

Relative poverty is associated with increased risk of diabetic ketoacidosis at onset of type 1 diabetes in children. A Swedish national population-based study in 2014-2019.

AIMS: The aim of the study was to estimate the effect of household relative poverty on the risk of diabetic ketoacidosis at diagnosis of children with type 1 diabetes using an international standard measurement of relative poverty. METHODS: A national population-based retrospective study was conducted. The Swedish National Diabetes Register (NDR) was linked with data from Sweden's public statistical agency (Statistics Sweden). Children who were diagnosed with new-onset type 1 diabetes in the period of 2014-2019 were common identifiers. The definition of diabetic ketoacidosis was venous pH <7.30 or a serum bicarbonate level <18 mmol/L. The exposure variable was defined according to the standard definition of the persistent at-risk-of-poverty rate used by the statistical office of the European Union (Eurostat) and several other European public statistical agencies. Univariate and multi-variable analyses were used to calculate the effect of relative poverty on the risk of diabetic ketoacidosis. RESULTS: Children from households with relative poverty had a 41% higher risk of diabetic ketoacidosis (1.41, CI 1.12-1.77, p = 0.004) and more than double the risk of severe diabetic ketoacidosis (pH <7.10) (RR 2.10, CI 1.35-3.25, p = 0.001), as compared to children from households without relative poverty. CONCLUSIONS: Relative poverty significantly increases the risk of diabetic ketoacidosis at onset of type 1 diabetes in children, even in a high-income country with publicly reimbursed health care.

CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review.

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.

Insulin pump therapy is associated with higher rates of mild diabetic ketoacidosis compared to injection therapy: A 2-year Swedish national survey of children and adolescents with type 1 diabetes.

OBJECTIVES: Diabetic ketoacidosis (DKA) in type 1 diabetes (T1D) can occur during both insulin pump therapy (continuous subcutaneous insulin infusion, CSII) and insulin injection therapy (multiple daily injections, MDI). The primary aim of this study was to compare CSII and MDI regarding DKA frequency. A secondary aim was to compare metabolic derangement between CSII and MDI at hospital admission for DKA. RESEARCH DESIGN AND METHODS: Children 0-17.99 years with established T1D admitted for DKA in Sweden from February 1, 2015 to January 31, 2017 were invited to participate. Data regarding demographics, laboratory data, CSII or MDI, and access to ketone meters and CGM were provided through questionnaires and medical records. The Swedish National Diabetes Registry (SWEDIABKIDS) was used to compare the distribution of CSII and MDI in the national population with the population admitted for DKA, using the chi-square goodness-of-fit test. Distribution of CSII and MDI was then categorized in clinical severity grades for mild (pH 7.20-7.29), moderate (pH 7.10-7.29) and severe DKA (pH <7.10). RESULTS: The distribution of CSII at DKA admission was significantly larger than in the national pediatric population with T1D (74.7% vs. 59.7%, p = 0.002). CSII was overrepresented in mild DKA (85.2% vs. with CSII, p < 0.001), but not in moderate/severe DKA (57.9% with CSII, p = 0.82). Mean HbA1c at hospital admission was 73.9 mmol/mol with CSII and 102.7 mmol/mol with MDI. CONCLUSIONS: CSII was associated with higher risk of mild DKA than MDI. MDI was associated with markedly higher HbA1c levels than CSII at hospital admission for DKA.

Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study.

AIMS/HYPOTHESIS: In individuals with type 1 diabetes, chronic hyperglycaemia impairs aerobic fitness. However, the effect of acute marked hyperglycaemia on aerobic fitness is unclear, and the impact of insulin level has not been examined. In this study, we explored if acute hyperglycaemia with higher or low insulin levels affects [Formula: see text] and other exercise performance indicators in individuals with type 1 diabetes. METHODS: Eligible participants were aged 14 to 30 years, with complication-free, type 1 diabetes and HbA1c ≤ 75 mmol/mol (≤9%). Participants exercised in a clinical laboratory under three clamp (constant insulin, variable glucose infusion) conditions: euglycaemia (5 mmol/l) with 20 mU [m2 BSA]-1 min-1 insulin (where BSA is body surface area) (Eu20); hyperglycaemia (17 mmol/l) with 20 mU [m2 BSA]-1 min-1 insulin (Hyper20); and hyperglycaemia (17 mmol/l) with 5 mU [m2 BSA]-1 min-1 insulin (Hyper5) on separate days. Participants and the single testing assessor were blinded to condition, with participants allocated to randomised testing condition sequences as they were consecutively recruited. Standardised testing (in order) conducted on each of the three study days included: triplicate 6 second sprint cycling, grip strength, single leg static balance, vertical jump and modified Star Excursion Balance Test, ten simple and choice reaction times and one cycle ergometer [Formula: see text] test. The difference between conditions in the aforementioned testing measures was analysed, with the primary outcome being the difference in [Formula: see text]. RESULTS: Twelve recreationally active individuals with type 1 diabetes (8 male, mean ± SD 17.9 ± 3.9 years, HbA1c 61 ± 11 mmol/mol [7.7 ± 1.0%], 7 ± 3 h exercise/week) were analysed. Compared with Eu20, [Formula: see text] was lower in Hyper20 (difference 0.17 l/min [95% CI 0.31, 0.04; p = 0.02] 6.6% of mean Eu20 level), but Hyper5 was not different (p = 0.39). Compared with Eu20, sprint cycling peak power was not different in Hyper20 (p = 0.20), but was higher in Hyper5 (64 W [95% CI 13, 115; p = 0.02] 13.1%). Hyper20 reaction times were not different (simple: p = 0.12) but Hyper5 reaction times were slower (simple: 11 milliseconds [95% CI 1, 22; p = 0.04] 4.7%) than Eu20. No differences between Eu20 and either hyperglycaemic condition were observed for the other testing measures (p > 0.05). CONCLUSIONS/INTERPRETATION: Acute marked hyperglycaemia in the higher but not low insulin state impaired [Formula: see text] but to a small extent. Acute hyperglycaemia had an insulin-dependent effect on sprint cycling absolute power output and reaction time but with differing directionality (positive for sprint cycling and negative for reaction time) and no effect on the other indicators of exercise performance examined. We find that acute hyperglycaemia is not consistently adverse and does not impair overall exercise performance to an extent clinically relevant for recreationally active individuals with type 1 diabetes. FUNDING: This research was funded by Diabetes Research Western Australia and Australasian Paediatric Endocrine Group grants.

Delayed referral is common even when new-onset diabetes is suspected in children. A Swedish prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes.

OBJECTIVE: Delayed treatment for new-onset diabetes Type 1 (T1D) can lead to diabetic ketoacidosis (DKA) with potentially devastating consequences. This prospective observational study aimed to characterize pediatric patients with DKA at hospital admission, regarding parental awareness of diabetes-related symptoms and delayed referrals from primary health care providers to pediatric emergency wards. RESEARCH DESIGN AND METHODS: Patients 0-18 years admitted to hospital with new-onset T1D and DKA between 2015 and 2017 were invited to participate. Questionnaires were filled out separately by the caregivers and by the attending hospital staff. Data from the Swedish National Diabetes Registry (SWEDIABKIDS) were used for comparison. Delayed referral was defined as a primary healthcare contact due to diabetes-related symptoms 0-4 weeks before hospital admission without immediate referral, or registered elevated glucose levels at primary healthcare centers without immediate referral. RESULTS: The study included 237 patients, among which parental suspicion of new-onset diabetes before healthcare contacts was reported in 39%. Parental suspicion of diabetes was associated with higher pH values at diagnosis. Patients in contact with primary health care providers before hospital admission had a delayed referral in 43% of the cases. Delayed referral was associated with lower pH values at hospital admission. Symptoms leading to primary healthcare contacts were similar regardless of whether delay occurred or not. CONCLUSIONS: Parental suspicion of diabetes was associated with milder DKA at hospital admission. Delayed referral was seen in a considerable proportion of children with primary healthcare contacts for symptoms associated with diabetes. Increased awareness of diabetes symptoms is of paramount importance.

The competitive athlete with type 1 diabetes.

Regular exercise is important for health, fitness and longevity in people living with type 1 diabetes, and many individuals seek to train and compete while living with the condition. Muscle, liver and glycogen metabolism can be normal in athletes with diabetes with good overall glucose management, and exercise performance can be facilitated by modifications to insulin dose and nutrition. However, maintaining normal glucose levels during training, travel and competition can be a major challenge for athletes living with type 1 diabetes. Some athletes have low-to-moderate levels of carbohydrate intake during training and rest days but tend to benefit, from both a glucose and performance perspective, from high rates of carbohydrate feeding during long-distance events. This review highlights the unique metabolic responses to various types of exercise in athletes living with type 1 diabetes. Graphical abstract.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. Graphical abstract.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.

Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis.

BACKGROUND: Our aim was to see if IV insulin therapy at diagnosis preserves beta-cell function better than multiple subcutaneous (SC) injections. METHODS: Fifty-four children 9.9 ± 3.5 years (range 2.8-14.9) without ketoacidosis were included in a 2 years, randomized multicenter study with insulin SC or 48 to 72 hours IV initially. Thirty-three (61%) were boys, 22 (41%) were pubertal. Forty-eight subjects completed 12 months follow-up and 43 completed 24 months. At 1, 6, 12, and 24 months, hemoglobin A1c (HbA1c), C-peptide and insulin/kg/24 h were measured. At 24 months, a mixed-meal tolerance test (MMTT) was performed. RESULTS: HbA1c at diagnosis was 10.7%, (93 mmol/mol) for IV, 10.7%, (94 mmol/mol) for SC. During the first 2 full days of insulin therapy, mean plasma glucose was 8.2 mmol/L for IV, 9.5 for SC (P = .025). Mean insulin dose was 1.5 U/kg/d for IV vs 1.0 for SC (P = .001). Sixteen (7 in IV, 9 in SC group) started with insulin pumps during the follow-up. At 24 months, we saw no significant differences: HbA1c (7.5%, 58 mmol/mol, for IV, 7.2%, 55 mmol/mol, for SC; ns), insulin doses (0.79 vs 0.88 U/kg/d; ns), fasting C-peptide (0.08 vs 0.12 nmol/L; ns), maximal MMTT response (0.19 vs 0.25 nmol/L; ns) and AUC (18.26 vs 23.9 nmol/L*min; ns). Peak C-peptide >0.2 nmol/L in the combined IV and SC groups correlated significantly with HbA1c and C-peptide at onset in a multiple regression. CONCLUSION: Residual beta cell function at 2 years seems to be independent from initial insulin regimens but related to HbA1c and C-peptide at onset.

Continuous subcutaneous insulin infusion: Special needs for children.

Continuous subcutaneous insulin infusion (CSII) is a very common therapy for children with type 1 diabetes. Due to physiological differences they have other requirements for their insulin pump than adults. The main difference is the need for very low basal rates. Even though most available insulin pumps reach a high accuracy at usual basal rates, accuracy decreases for lower rates. In addition, the lowest delivered amount at 1 time is limiting the fine tuning of the basal rate as well as the option for temporary basal rates. Alarms in case of occlusions depend on accumulation of a certain amount of insulin in the catheter, and therefore the time until such an alarm is triggered is much longer with lower basal rates. Accordingly, the risk for hyperglycemia developing into diabetic ketoacidosis increases. The availability of bolus advisors facilitates the calculation of meal and correction boluses for children and their parents. However, there are some differences between the calculators, and the settings that the calculation is based on are very important. Better connectivity, for example with a system for continuous glucose monitoring, might help to further increase safety in the use of CSII in children. When selecting an insulin pump for a child, the features and characteristics of available pumps should be properly compared to ensure an effective and safe therapy.

Evaluation of glucose control when a new strategy of increased carbohydrate supply is implemented during prolonged physical exercise in type 1 diabetes.

PURPOSE: In healthy individuals, high carbohydrate intake is recommended during prolonged exercise for maximum performance. In type 1 diabetes (T1D), this would alter the insulin requirements. The aim of the study was to evaluate the safety of high glucose supplementation during prolonged exercise and the glucose control when a novel strategy of increased carbohydrate supply was implemented during prolonged exercise in T1D. METHODS: Eight subjects with T1D participated in a sports camp including sessions of prolonged exercise and individualized feedback during three consecutive days. This was later followed by a 90 km cross-country skiing race. Large amounts of carbohydrates, 75 g/h, were supplied during exercise and the insulin requirements were registered. Glucose was measured before, during and after exercise aiming at euglycaemia, 4-8 mmol/L (72-144 mg/dL). During the race, continuous glucose monitoring (CGM) was used as an aspect of safety and to allow direct and individual adjustments. RESULTS: Compared to ordinary carbohydrate supply during exercise, the high carbohydrate supplementation resulted in significantly increased insulin doses to maintain euglycaemia. During the cross-country skiing race, the participants succeeded to reach mean target glucose levels; 6.5 ± 1.9 mmol/L (117 ± 34 mg/dL) and 5.7 ± 1.5 mmol/L (103 ± 27 mg/dL) at the start and finish of the race, respectively. Episodes of documented hypoglycemia (<4 mmol/L/72 mg/dL) were rare. CGM was used for adjustments. CONCLUSION: In this study, large carbohydrate supplementation in T1D individuals during prolonged aerobic exercise is safe and allows the subjects to maintain glycaemic control and indicates the feasibility of CGM under these conditions.

Automated Insulin Delivery Systems in Pediatric Type 1 Diabetes: A Narrative Review.

This narrative review assesses the use of automated insulin delivery (AID) systems in managing persons with type 1 diabetes (PWD) in the pediatric population. It outlines current research, the differences between various AID systems currently on the market and the challenges faced, and discusses potential opportunities for further advancements within this field. Furthermore, the narrative review includes various expert opinions on how different AID systems can be used in the event of challenges with rapidly changing insulin requirements. These include examples, such as during illness with increased or decreased insulin requirements and during physical activity of different intensities or durations. Case descriptions give examples of scenarios with added user-initiated actions depending on the type of AID system used. The authors also discuss how another AID system could have been used in these situations.

Patterns and Predictors Associated With Long-Term Glycemic Control in Pediatric and Young Adult Patients with Type 1 Diabetes.

BACKGROUND: The development of diabetes technology is rapid and requires education and resources to be successfully implemented in diabetes care management. METHOD: In an observational study, we evaluated the use of advanced diabetes technology, resource utilization, and glycemic control. The study population was 725 individuals with type 1 diabetes (T1D) living in Region Halland, Sweden. The study cohort was followed for 7 years between 2013 and 2019. RESULTS: Children aged 0 to 17 years were associated with significantly better glucose control than young adults aged 18 to 25 years. The mean HbA1c in children and young adults was 53 mmol/mol (7.0%) compared to 61 mmol/mol (7.7%) (P < .0001), respectively. Comorbidities such as attention deficit hyperactivity disorder (ADHD), autism, and coelic disease were associated with higher HbA1c. All groups, regardless of age and comorbidity, showed a positive effect on glucose control after visiting a dietitian or psychologist. Differences were found between the age groups in terms of more use of advanced diabetes technology and more frequent visits to a physician in children compared to young adults. CONCLUSIONS: More frequent visits to physicians, and a visit to dietitians, and psychologists were associated with improved glucose control in individuals with T1D 0 to 25 years. Increased resources, including access to more advanced technologies, may be required in young adults with T1D.

Hormonal response during physical exercise of different intensities in adolescents with type 1 diabetes and healthy controls.

BACKGROUND: Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges. OBJECTIVE: To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO(2) max) and hormonal response to physical exercise of different intensities. SUBJECTS: Twelve individuals (six boys and six girls; age 14-19 yr, pubertal stage 4-5) with type 1 diabetes (duration, 6.3 ± 4.4 yr; hemoglobin A1c, 63 ± 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity. METHODS: During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously. RESULTS: VO(2) max did not differ between the groups, diabetes 49.8 ± 9.9 vs. control 50.7 ± 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 ± 27.0 vs. control 33.8 ± 20.9 mU/L, p < 0.05. CONCLUSIONS: Physical capacity and hormonal regulation of blood glucose in connection with physical exercise of different intensities did not differ between adolescents with diabetes and healthy controls. Thus, adolescents with type 1 diabetes can participate in physical activity on the same terms as healthy peers.