Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes.

BACKGROUND: The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. METHODS: In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed. RESULTS: A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred. CONCLUSIONS: A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).

Parents' experiences of using remote monitoring technology to manage type 1 diabetes in very young children during a clinical trial: Qualitative study.

AIMS: To explore parents' experiences of using remote monitoring technology when caring for a very young child with type 1 diabetes during a clinical trial. METHODS: Interviews were conducted with parents of 30 children (aged 1-7 years) participating in a trial (the KidsAP02 study) comparing hybrid closed-loop insulin delivery with sensor-augmented pump therapy. In both arms, parents had access to remote monitoring technology. Data analysis focused on identification of descriptive themes. RESULTS: Remote monitoring technology gave parents improved access to data which helped them pre-empt and manage glucose excursions. Parents observed how, when children were in their own care, they could be more absent while present, as their attention could shift to non-diabetes-related activities. Conversely, when children were others' care, remote monitoring enabled parents to be present while absent, by facilitating oversight and collaboration with caregivers. Parents described how remote monitoring made them feel more confident allowing others to care for their children. Parents' confidence increased when using a hybrid closed-loop system, as less work was required to keep glucose in range. Benefits to children were also highlighted, including being able to play and sleep uninterrupted and attend parties and sleepovers without their parents. While most parents welcomed the increased sense of control remote monitoring offered, some noted downsides, such as lack of respite from caregiving responsibilities. CONCLUSIONS: Remote monitoring can offer manifold benefits to both parents and very young children with type 1 diabetes. Some parents, however, may profit from opportunities to take 'time out'.

Metabolic control during the SARS-CoV-2 lockdown in a large German cohort of pediatric patients with type 1 diabetes: Results from the DPV initiative.

OBJECTIVE: To assess if metabolic control worsened during the SARS-CoV2 lockdown in spring 2020 in youth with type 1 diabetes (T1D) in Germany. METHODS: Data from 19,729 pediatric T1D patients from the diabetes prospective follow-up (DPV) registry were available. Data sets from four time-periods between January 1 and June 30, 2020, were compared with data from the whole year 2019 in the same patient; differences were adjusted for seasonality, increasing age, and longer diabetes duration. HbA1c values from laboratory measurements and estimates derived from continuous glucose monitoring (CGM) were aggregated into a combined glucose indicator (CGI), expressed in analogy to HbA1c. RESULTS: Based on regression models adjusted for differences of sex, age, diabetes duration, and migratory background between the four time-periods, CGI values in 2020 were slightly higher than in 2019, for example, by 0.044% (0.042-0.046) (median [95% CI]) in the second lockdown month, time-period 3. Insulin dose and BMI-SDS were also marginally higher. In 2020, there were fewer hospitalizations (e.g., incidence risk ratio in time-period 3 compared with 2019: 0.52 [95% CI: 0.46-0.58]). In a subgroup of patients reporting CGM data in both years, metrics in 2020 improved: time in target increased, and mean sensor glucose fell, for example, by 2.8% (2.7-2.9), and by 4.4 mg/dl (4.3-4.6) in time-period 3. CONCLUSION: Before, during, and after the lockdown in spring 2020, metabolic control in youth with T1D in Germany did not differ significantly from the preceding year. Further effects of the ongoing pandemic on pediatric T1D patients need to be evaluated.

Parents' views about healthcare professionals having real-time remote access to their young child's diabetes data: Qualitative study.

OBJECTIVES: We explored parents' views about healthcare professionals having remote access to their young child's insulin and glucose data during a clinical trial to inform use of data sharing in routine pediatric diabetes care. RESEARCH DESIGN AND METHODS: Interviews with 33 parents of 30 children (aged 1-7 years) with type 1 diabetes participating in a randomized trial (KidsAP02) comparing hybrid closed-loop system use with sensor-augmented pump therapy. Data were analyzed using a qualitative descriptive approach. RESULTS: Parents reported multiple benefits to healthcare professionals being able to remotely access their child's glucose and insulin data during the trial, despite some initial concerns regarding the insights offered into everyday family life. Key benefits included: less work uploading/sharing data; improved consultations; and, better clinical input and support from healthcare professionals between consultations. Parents noted how healthcare professionals' real-time data access facilitated remote delivery of consultations during the COVID-19 pandemic, and how these were more suitable for young children than face-to-face appointments. Parents endorsed use of real-time data sharing in routine clinical care, subject to caveats regarding data access, security, and privacy. They also proposed that, if data sharing were used, consultations for closed-loop system users in routine clinical care could be replaced with needs-driven, ad-hoc contact. CONCLUSIONS: Real-time data sharing can offer clinical, logistical, and quality-of-life benefits and enhance opportunities for remote consultations, which may be more appropriate for young children. Wider rollout would require consideration of ethical and cybersecurity issues and, given the heightened intrusion on families' privacy, a non-judgmental, collaborative approach by healthcare professionals.

Pharmacotherapy of Children and Adolescents with Type 1 Diabetes Mellitus.

Insulin treatment in children and adolescents with autoimmune type 1 diabetes has changed tremendously in the last 20 years with the knowledge of DCCT trial regarding near-normal glucose levels on the micro- and macrovascular outcome. Intensified insulin therapy is now standard of care. Carb counting however was introduced systematically only recently in several countries. In industrialized countries most patients in this age group are treated with continuous subcutaneous insulin injections. Nowadays this is combined with continuous subcutaneous glucose measurement commencing sensor-augmented pump therapy. Predictive low glucose suspend reduces the frequency of hypoglycemic events. Still not available for children is a commercially available closed loop system. However, treatment goals are still frequently not reached especially in the group of adolescents. Therefore several additive drugs are tested to improve treatment results. There are new insulins with faster and longer action profile in the pipeline to better mimic physiologic insulin profiles. Smart insulins may be able to mimic reaction on blood sugar levels. The broad facet of treatment modalities helps pediatric diabetes teams to individualize therapy and so improve patients' health-related quality of life.

Pharmacotherapy of Children and Adolescents with Type 2 Diabetes Mellitus.

Increasing obesity and overweight has led to increased prevalence of type 2 diabetes mellitus (T2D) in adolescents and young adults all over the world. Overweight naturally reduces insulin sensitivity. The following permanent insulin resistance can be found even in younger obese children. Beta-cell insufficiency following high insulin production over years leads to impaired glucose tolerance and later type 2 diabetes mellitus. In children and adolescents, the diagnosis of T2D is often made by screening very obese patients with oral glucose tolerance test. Usually in these patients, few or no diabetes symptoms are found. As frequently found in pediatric pharmacotherapy, only a few of the modern substances used in adults are available for pediatric patients with type 2 diabetes mellitus. The essential change in lifestyle for weight reduction is difficult in this age group with often rather disappointing results.

Review of Leipzig protocol for intravenous insulin infusion in pediatric patients with type 1 diabetes during intercurrent illness and surgery.

OBJECTIVE: Continuous intravenous (IV) insulin infusion therapy minimizes blood glucose (BG) fluctuations and prevents metabolic deterioration in pediatric patients with type 1 diabetes (T1D) during intercurrent illness and surgery. However, data on the adequate fluid and insulin substitution in this situation is rare. We evaluated the effectiveness and safety of IV insulin therapy according to our local protocol. METHODS: Retrospective study of 124 cases of hospitalization with IV insulin therapy because of intercurrent illness (n = 78) or minor surgery (n = 46) in 62 patients with T1D (mean age: 9.6 ± 5.4 years). The patients received a glucose-electrolyte infusion and short-acting insulin (normal insulin). Infusion rate was adapted according to the BG measured hourly. Glycemic control was analyzed in subgroups subdivided by age, glycated hemoglobin (HbA1c) and reason for hospitalization. RESULTS: Mean infusion time was 22 hours (range 1.5-147 hours). In 65% of the infusion time, patients' BG was within the target range (4-8 mmol/L). Critical events (BG <3 or > 15 mmol/L) were found in 6% of the infusion time. Comparison of glycemic control in subgroups for HbA1c and the reason for hospitalization revealed no significant differences. However, patients aged <12 years exhibited significant more critical events, primarily hypoglycemia compared to adolescents (hypoglycemia/case 2.4 ± 2.7 vs 0.9 ± 2.0; P < 0.001). CONCLUSIONS: Our protocol for IV insulin therapy proved to be appropriate for adequate glycemic control in pediatric patients with T1D during intercurrent illness and surgery. However, the regime seems to be more suitable in adolescents. We adapted our protocol in younger patients with reduction of the insulin dose.

Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes.

OBJECTIVE: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery. METHODS: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored. RESULTS: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. CONCLUSIONS: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.

Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries.

AIMS/HYPOTHESIS: While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries. METHODS: Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n = 26,198), T1D Exchange (T1DX; n = 13,755) and the National Paediatric Diabetes Audit (NPDA; n = 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared. RESULTS: The overall mean HbA1c level was higher in the NPDA (8.9 ± 1.6% [74 ± 17.5 mmol/mol]) than in the DPV (8.0 ± 1.6% [64 ± 17.0 mmol/mol], p < 0.001) and T1DX (8.3 ± 1.4% [68 ± 15.4 mmol/mol], p < 0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%, p < 0.001) and T1DX (47%, p < 0.001). In a pooled analysis, pump use was associated with a lower mean HbA1c (pump: 8.0 ± 1.2% [64 ± 13.3 mmol/mol] vs injection: 8.5 ± 1.7% [69 ± 18.7 mmol/mol], p < 0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (p < 0.001) and boys were treated with a pump less often compared with girls (p < 0.001). CONCLUSIONS/INTERPRETATION: Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.

Association between IgE-mediated allergies and diabetes mellitus type 1 in children and adolescents.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by an immunological reaction that is dominated by type-1 T helper (Th1) cells, whereas immunoglobulin E (IgE)-mediated allergies are associated with Th2 cell. According to the Th1/Th2-hypothesis, the immune system is said to either develop into the direction of Th1 or Th2 cells. This would mean that a child developing T1DM is unlikely to develop an IgE-mediated allergy and vice versa. OBJECTIVE: The aim of the study was to investigate the association between the prevalence of T1DM and IgE-mediated allergies. METHODS: We designed a prospective case control study with 94 children and adolescents with T1DM and 188 age- and sex-matched control children. The basis of our investigations was a questionnaire concerning the family and children's history as to the presence of IgE-mediated allergies. Moreover, the following blood investigations were done: total serum IgE, specific IgE antibodies to major inhalant allergens, and a multiplex cytokine analysis measuring levels of specific cytokines representing either Th1- or Th2- cytokines. RESULTS: Children with T1DM reported the presence of IgE-mediated allergies significantly more often than children of the control group. Children with T1DM had significantly higher tumor necrosis factor alpha (TNFα) levels than healthy controls. Levels of interleukin-2 (IL-2) and IL-6 were higher in the groups of children with the presence of a personal history of allergies, regardless of the presence of T1DM. CONCLUSIONS: Our results suggest that T1DM is associated with a higher risk of a self-reported presence of IgE-mediated allergies and that the Th1/Th2-hypothesis may be an oversimplification.

Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries.

AIMS/HYPOTHESIS: The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old. METHODS: Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared. RESULTS: Insulin pump use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%, p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The frequency of SH did not differ between registries or by HbA1c, whereas the frequency of DKA was higher for the T1DX and greater in those with higher HbA1c levels. CONCLUSIONS/INTERPRETATION: DPV data indicate that an HbA1c of <7.5% can frequently be achieved in children with type 1 diabetes who are under 6 years old. An improved metabolic control of type 1 diabetes in young patients appears to decrease the risk of DKA without increasing SH. The greater frequency of suboptimal control in young patients in the T1DX compared with the DPV is not fully explained by a less frequent use of insulin pumps and may relate to the higher HbA1c targets that are recommended for this age group in the USA.

Using person reported outcomes: Psychometric properties of the German diabetes treatment satisfaction questionnaire (DTSQ) for teens and parents.

Aims: To examine psychometric properties including the factor structure of the German versions of the Diabetes Treatment Satisfaction Questionnaire for teens and parents (DTSQ-T/-P). Methods: Linguistically validated questionnaires were completed by 363 adolescents with type 1 diabetes and 655 parent-caregivers in a multicenter study. Confirmatory factor analysis (CFA), reliability, and correlations were examined. Results: CFA confirmed the 2-factor model of treatment satisfaction (TS) & perceived diabetes control (PDC) with an adjustment of removing the "medical support" item from the TS and examining it as a single item in this study. Cronbach's α of TS for DTSQ-T/-P was 0.82 & 0.83, respectively, and α of the two-item PDC factor was 0.70 & 0.60, respectively. The DTSQ scale scores positively correlated with time in range and inversely correlated with HbA1c. Scale scores of DTSQ-T/-P showed significantly positive relations to the KIDSCREEN-10 Index and negative associations with the Problem Areas in Diabetes (PAID). The TS of the parents was correlated with depressive symptoms measured in the Patient Health Questionnaire-9. Conclusions: The DTSQ-T/-P produced psychometrically sound scores in measuring diabetes treatment satisfaction in German teens with type 1 diabetes and their parents. German DTSQ versions for teens and parents are recommended in research and clinical practice.

Assessing Parental Competence and Self-Ratings in Management of Pediatric Type 1 Diabetes and Emergency Glucagon Administration-An Exploratory Observational Study.

BACKGROUND: Parents of pediatric patients with type I diabetes require competence in hypoglycemia management and skills in glucagon administration to deal with potentially life-threatening severe hypoglycemia. We aimed to compare parents' subjective self-ratings to an objective expert assessment of competences and skills in dealing with severe hypoglycemia. METHODS: We interviewed 140 participants to assess their subjective self-ratings. The objective expert assessments used a standardized clinical case scenario of severe hypoglycemia and a practical demonstration of glucagon administration. RESULTS: The participants self-rated their competence in hypoglycemia management as good (5) or very good (6), and their skills in administering glucagon as acceptable (3) [Scale: very poor (1) to very good (6)]. In the standardized clinical case scenario, 1.4% (2/140) of participants named all relevant steps of severe hypoglycemia management. In the practical demonstration of glucagon administration, 92.9% (130/140) of participants committed at least one drug handling error; 52.1% (73/140) committed at least one drug handling error rated with high clinical risk. CONCLUSIONS: We found discrepancies regarding participants' subjective self-ratings compared to their performance in the respective objective expert assessments. These discrepancies indicate a lack of error awareness and the need for intervention studies to improve competence in hypoglycemia management and glucagon administration.

Time Spent in Hypoglycemia According to Age and Time of Day: Observations During Closed-Loop Insulin Delivery.

Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.

Parents' experiences of using a hybrid closed-loop system (CamAPS FX) to care for a very young child with type 1 diabetes: Qualitative study.

AIMS: To explore parents' experiences of using a hybrid closed-loop system (CamAPS FX) when caring for a very young child (aged 1-7 years) with type 1 diabetes. METHODS: Interviews with n = 33 parents of 30 children who used the system during a randomised controlled trial. Data analysis used a descriptive thematic approach. RESULTS: While some parents were initially reticent about handing control to the system, all reported clinical benefits to using the technology, having to do less diabetes-related work and needing less clinical input over time. Parents welcomed opportunities to enhance the system's efficacy (using Ease-off and Boost functions) as required. Parents described how the system's automated glucose control facilitated more normality, including sleeping better, worrying less about their child, and feeling more confident and able to outsource care. Parents also described more normality for the child (alongside better sleep, mood and concentration, and lessened distress) and siblings. Parents liked being able to administer insulin using a smartphone, but suggested refinements to device size and functionality. CONCLUSIONS: Using a hybrid closed-loop system in very young children can facilitate greater normality and may result in a lessened demand for health professionals' input. Systems may need to be customised for very young children.

Cambridge Hybrid Closed-Loop System in Very Young Children With Type 1 Diabetes Reduces Caregivers' Fear of Hypoglycemia and Improves Their Well-Being.

OBJECTIVE: To evaluate the impact of CamAPS FX hybrid closed-loop (HCL) automated insulin delivery in very young children with type 1 diabetes (T1D) on caregivers' well-being, fear of hypoglycemia, and sleepiness. RESEARCH DESIGN AND METHODS: We conducted a multinational, open-label, randomized crossover study. Children (age 1-7 years) with T1D received treatment for two 4-month periods in random order, comparing HCL with sensor augmented pump (control). At baseline and after each treatment period, caregivers were invited to complete World Health Organization-Five Well-Being Index, Hypoglycemia Fear Survey, and Epworth Sleepiness Scale questionnaires. RESULTS: Caregivers of 74 children (mean ± SD age 5 ± 2 years and baseline HbA1c 7.3 ± 0.7%; 42% female) participated. Results revealed significantly lower scores for hypoglycemia fear (P < 0.001) and higher scores for well-being (P < 0.001) after HCL treatment. A trend toward a reduction in sleepiness score was observed (P = 0.09). CONCLUSIONS: Our results suggest better well-being and less hypoglycemia fear in caregivers of very young children with T1D on CamAPS FX HCL.

Safety of User-Initiated Intensification of Insulin Delivery Using Cambridge Hybrid Closed-Loop Algorithm.

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.

Evaluating the Impact of Applying Personal Glucose Targets in a Closed-Loop System for People With Type 1 Diabetes.

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.

Early versus delayed insulin pump therapy in children with newly diagnosed type 1 diabetes: results from the multicentre, prospective diabetes follow-up DPV registry.

BACKGROUND: Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. METHODS: We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. FINDINGS: Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1-8·7 in the early group; 5·0-8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8-7·9] and 62·6 mmol/mol [95% CI 62·1-63·2] vs 8·0% [8·0-8·1] and 64·1 mmol/mol [63·6-64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24-0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78-0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2-117·9) versus 118·5 mm Hg (118·2-118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2-63·5) versus 60·6 mg/dL (60·0-61·2), p<0·0001; however, diastolic blood pressure; concentrations of LDL cholesterol, non-HDL cholesterol, and triglycerides; and estimated body-mass index standard deviation scores during follow-up did not differ significantly between both groups. INTERPRETATION: Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. FUNDING: The German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.

Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol.

INTRODUCTION: Diabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group. METHODS AND ANALYSIS: The study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1-7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1-4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants' and caregivers' experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed. ETHICS AND DISSEMINATION: Ethics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d'Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03784027.