Demographic, Clinical, Management, and Outcome Characteristics of 8,004 Young Children With Type 1 Diabetes.

OBJECTIVE: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes age <6 years across three international registries: Diabetes Prospective Follow-Up Registry (DPV; Europe), T1D Exchange Quality Improvement Network (T1DX-QI; U.S.), and Australasian Diabetes Data Network (ADDN; Australasia). RESEARCH DESIGN AND METHODS: An analysis was conducted comparing 2019-2021 prospective registry data from 8,004 children. RESULTS: Mean ± SD ages at diabetes diagnosis were 3.2 ± 1.4 (DPV and ADDN) and 3.7 ± 1.8 years (T1DX-QI). Mean ± SD diabetes durations were 1.4 ± 1.3 (DPV), 1.4 ± 1.6 (T1DX-QI), and 1.5 ± 1.3 years (ADDN). BMI z scores were in the overweight range in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN) of participants. Mean ± SD HbA1c varied among registries: DPV 7.3 ± 0.9% (56 ± 10 mmol/mol), T1DX-QI 8.0 ± 1.4% (64 ± 16 mmol/mol), and ADDN 7.7 ± 1.2% (61 ± 13 mmol/mol). Overall, 37.5% of children achieved the target HbA1c of <7.0% (53 mmol/mol): 43.6% in DPV, 25.5% in T1DX-QI, and 27.5% in ADDN. Use of diabetes technologies such as insulin pump (DPV 86.6%, T1DX 46.6%, and ADDN 39.2%) and continuous glucose monitoring (CGM; DPV 85.1%, T1DX-QI 57.6%, and ADDN 70.5%) varied among registries. Use of hybrid closed-loop (HCL) systems was uncommon (from 0.5% [ADDN] to 6.9% [DPV]). CONCLUSIONS: Across three major registries, more than half of children age <6 years did not achieve the target HbA1c of <7.0% (53 mmol/mol). CGM was used by most participants, whereas insulin pump use varied across registries, and HCL system use was rare. The differences seen in glycemia and use of diabetes technologies among registries require further investigation to determine potential contributing factors and areas to target to improve the care of this vulnerable group.

Impact of a 4-week intensive track and field training intervention on glycaemia in adolescents with type 1 diabetes: The ChilDFiT1 study.

AIM: To investigate the safety and efficacy of track and field training compared with intensification of insulin treatment only in adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: Eighteen adolescents (seven females) with T1D were included (age 15.1 ± 1.1 years, HbA1c 7.3% ± 1.0% [56.3 ± 10.9 mmol/mol]). After a 4-week observational control phase, participants were randomized to either stand-alone intensive glycaemic management (IT; telemedicine or on-site visits, three times/week) or additionally performed track and field exercise (EX; three 60-minute sessions/week) for 4 weeks. Glycaemia was assessed via continuous glucose monitoring during observational control and intervention phases. RESULTS: Time in range (70-180 mg/dL; 3.9-10.0 mmol/L) significantly improved from the observational control phase to the exercise intervention phase in EX (69% ± 13% vs. 72% ± 11%, P = .049), but not in IT (59% ± 22% vs. 62% ± 16%, P = .399). Time below range 1 (54-69 mg/dL; < 3.9 mmol/L) improved in IT (3.1% ± 1.9% vs. 2.0% ± 0.8%, P = .017) and remained stable in EX (2.0% ± 1.7 vs. 1.9% ± 1.1%, P = .999). The EX group's HbA1c ameliorated preintervention to postintervention (mean difference: ΔHbA1c -0.19% ± 0.17%, P = .042), which was not seen within the IT group (ΔHbA1c -0.16% ± 0.37%, P = .40). Glucose standard deviation was reduced significantly in EX (55 ± 11 vs. 51 ± 10 mg/dL [3.1 ± 0.6 vs. 2.8 ± 0.6 mmol/L], P = .011), but not in IT (70 ± 24 vs. 63 ± 18 mg/dL [3.9 ± 1.3 vs. 3.5 ± 1.0 mmol/L], P = .186). CONCLUSION: Track and field training combined with intensive glycaemic management improved glycaemia in adolescents with T1D, which was not observed in the non-exercise group.

SPIOMET4HEALTH-efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5-10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. DISCUSSION: The present study will be the first to evaluate-in a randomised, double-blind, placebo-controlled way-the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. TRIAL REGISTRATION: EudraCT 2021-003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .

A Comparison of Faster Insulin Aspart with Standard Insulin Aspart Using Hybrid Automated Insulin Delivery System in Active Children and Adolescents with Type 1 Diabetes: A Randomized Double-Blind Crossover Trial.

Objective: To evaluate the use of faster acting (FIA) and standard insulin aspart (SIA) with hybrid automated insulin delivery (AID) in active youth with type 1 diabetes. Research Design and Methods: In this double-blind multinational randomized crossover trial, 30 children and adolescents with type 1 diabetes (16 females; aged 15.0 ± 1.7 years; baseline HbA1c 7.5% ± 0.9% [58 ± 9.8 mmol/mol]) underwent two unrestricted 4-week periods using hybrid AID with either FIA or SIA in random order. During both interventions, participants were using the hybrid AID (investigational version of MiniMed™ 780G; Medtronic). Participants were encouraged to exercise as frequently as possible, capturing physical activity with an activity monitor. The primary outcome was the percentage of sensor glucose time above range (180 mg/dL [10.0 mmol/L]) measured by continuous glucose monitoring. Results: In an intention-to-treat analysis, mean time above range was 31% ± 15% at baseline, 19% ± 6% during FIA use, and 20% ± 6% during SIA use with no difference between treatments: mean difference = -0.9%; 95% CI: -2.4% to 0.6%; P = 0.23. Similarly, there was no difference in mean time in range (TIR) (78% and 77%) or median time below range (2.5% and 2.8%). Glycemic outcomes during exercise or postprandial periods were comparable for the two treatment arms. No severe hypoglycemia or diabetic ketoacidosis events occurred. Conclusions: FIA was not superior to SIA with hybrid AID system use in physically active children and adolescents with type 1 diabetes. Nonetheless, both insulin formulations enabled high overall TIR and low time above and below ranges, even during and after documented exercise. Trial Registration Clinicaltrials.gov: NCT04853030.

Rare Antagonistic Leptin Variants and Severe, Early-Onset Obesity.

Hormone absence or inactivity is common in congenital disease, but hormone antagonism remains controversial. Here, we characterize two novel homozygous leptin variants that yielded antagonistic proteins in two unrelated children with intense hyperphagia, severe obesity, and high circulating levels of leptin. Both variants bind to the leptin receptor but trigger marginal, if any, signaling. In the presence of nonvariant leptin, the variants act as competitive antagonists. Thus, treatment with recombinant leptin was initiated at high doses, which were gradually lowered. Both patients eventually attained near-normal weight. Antidrug antibodies developed in the patients, although they had no apparent effect on efficacy. No severe adverse events were observed. (Funded by the German Research Foundation and others.).

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.

[Antihyperglycemic treatment guidelines for diabetes mellitus type 2 (Update 2023)]. / Antihyperglykämische Therapie bei Diabetes mellitus Typ 2 (Update 2023).

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.

[Insulin pump therapy and continuous glucose monitoring]. / Diabetestechnologie (Update 2023).

This Guideline represents the recommendations of the Austrian Diabetes Association (ÖDG) on the use of diabetes technology (insulin pump therapy; continuous glucose monitoring, CGM; hybrid closed-loop systems, HCL; diabetes apps) and access to these technological innovations for people with diabetes mellitus based on current scientific evidence.

[Diabetes mellitus in childhood and adolescence (Update 2023)]. / Diabetes mellitus im Kindes- und Jugendalter (Update 2023).

In contrast to adults, type 1 diabetes mellitus (T1D) is the most frequent form of diabetes in childhood and adolescence (> 90%). After diagnosis the management of children and adolescents with T1D should take place in highly specialized pediatric units experienced in pediatric diabetology. The lifelong substitution of insulin is the cornerstone of treatment whereby modalities need to be individually adapted for patient age and the family routine. In this age group the usage of diabetes technology (glucose sensors, insulinpumps and recently hybrid-closed-loop-systems) is recommended. An optimal metabolic control right from the start of therapy is associated with an improved long-term prognosis. Diabetes education is essential in the management of patients with diabetes and their families and needs to be performed by a multidisciplinary team consisting of a pediatric diabetologists, diabetes educator, dietitian, psychologist and social worker. The Austrian working group for pediatric endocrinology and diabetes (APEDÖ) and the ISPAD (International Society for Pediatric and Adolescent Diabetes) recommend a metabolic goal of HbA1c ≤ 7.0%, ((IFCC) < 53 mmol/mol), and a "Time in range" > 70% for all pediatric age groups without the presence of severe hypoglycemia. Age-related physical, cognitive and psychosocial development, screening for associated diseases, avoidance of acute diabetes-related complications (severe hypoglycemia, diabetic ketoacidosis) and prevention of diabetes-related late complications to ensure high quality of life are the main goals of diabetes treatment in all pediatric age groups.

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.

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.

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.

Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes.

AIM: Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed. METHODS: This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis. RESULTS: Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period. CONCLUSIONS: Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

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.

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'.

Alarming Increase of Ketoacidosis Prevalence at Type 1 Diabetes-Onset in Austria-Results From a Nationwide Registry.

OBJECTIVE: We analyzed the annual prevalence of onset-DKA (diabetic ketoacidosis) from 2012 to 2020 with a sub-analysis for lockdown-periods during the COVID-19 pandemic in 2020. DESIGN: All newly diagnosed children with type 1 diabetes (T1D) aged <15 years are prospectively registered in the population-based Austrian Diabetes Incidence Study in Austria. MAIN OUTCOME MEASURES: The annual DKA prevalence was analyzed using Joinpoint regression. Definition of DKA: pH <7.3, mild DKA: pH 7.3 to ≤ 7.1, severe DKA: pH <7.1. DKA prevalence during the lockdown periods in 2020 and the corresponding periods in 2015-2019 were examined using Fisher's exact test. RESULTS: In the years 2012-2020 the mean prevalence for onset-DKA in Austria was 43.6% [95%CI (confidence interval): 41.6, 45.7] and thus above the mean prevalence of previous decades (1989-2011) of 37,1 % (95%CI: 35.6, 38.6). A particularly high prevalence was found among children <2 years of age (72.0% DKA, 32.8% severe DKA). No significant gender difference was found. Prevalence of severe DKA at T1D-onset increased significantly since 2015 (p = 0.023). During the lockdown in 2020, 59.3% of children were diagnosed with DKA at T1D-onset, compared to 42.1% during the previous 5 years (p = 0.022). Moreover, 20% of children had severe DKA at T1D diagnosis, compared to 14% during the comparison period. CONCLUSIONS: The previously already high prevalence of DKA at T1D-onset has further increased over time. The COVID-19 pandemic has exacerbated the problem of a late or delayed diagnosis of diabetes in children resulting in onset-DKA. The alarmingly increased prevalence of DKA in Austrian children with T1D calls for urgent action.

[Emergency card, emergency medication, and information leaflet for the prevention and treatment of adrenal crisis (Addison crisis): an Austrian consensus document]. / Notfallausweis, Notfallmedikation und Informationsmaterial zur Prävention und Therapie der Nebennierenkrise (Addison-Krise): Ein österreichisches Konsensusdokument.

A central goal of the adrenal insufficiency management is the prevention of acute adrenal insufficiency (also known as adrenal crisis or Addison crisis). This consensus document was generated in order to achieve better implementation and harmonization of measures for the prevention and treatment of acute adrenal insufficiency in Austria. The following measures are generally recommended for all patients with adrenal insufficiency and are outlined in this manuscript: (1) Provision of a "steroid emergency card" and possibly also a medical alert bracelet or necklace (or similar identification). (2) Provision of a hydrocortisone injection kit (or alternative glucocorticoid preparations) for emergency use plus sufficient oral glucocorticoid doses for stress situations/illness. (3) Education of patients and relatives on glucocorticoid stress dosing and "sick day rules" as well as on self-injection of hydrocortisone. (4) Provision of a treatment guideline (information leaflet) for the prevention and therapy of the adrenal crisis, which should also be shown to healthcare staff if necessary. (5) Provision of an emergency phone number (contact details) of the responsible endocrine specialist team or other trained staff. (6) Reinforcement of patient education on a regular basis (preferably yearly). This consensus document also includes recommendations for glucocorticoid dosing in the perioperative setting as well as in various other stress situations.

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.).