Experiences of adolescents and young adults with type 1 diabetes and chronically elevated glucose levels following the transition from multiple daily injections to advanced hybrid closed-loop: A qualitative study.

AIM: To understand experiences of using second-generation advanced hybrid closed-loop (AHCL) therapy in adolescents and young adults with chronically elevated glucose levels who were previously using multiple daily injections (MDI) therapy. METHOD: Semi-structured interviews with participants aged 13-25 years, on AHCL therapy for 3 months as part of a single-arm prospective study. Key inclusions: HbA1c ≥69 mmol/mol (8.5%); diabetes duration ≥1 year; and using MDI therapy prior to the study. Qualitative content analysis was used to identify themes and subthemes. RESULTS: Interviews were conducted among 14 participants with mean age 19.4 ± 4.3 years and mean baseline HbA1c 90 ± 25 mmol/mol (10.4 ± 4.5%). Three themes were identified: (1) substantially improved glucose levels improved perceptions of overall health; (2) features of AHCL aid in adoption and ongoing self-management; and (3) burden of care was reduced through automation of insulin delivery. Overall, there were positive impacts on physical, mental and social well-being. Participants were willing to overlook minor frustrations with AHCL because of the vast benefits that they had experienced. Four participants reported transient pseudo-hypoglycaemia: symptoms of hypoglycaemia when objectively measured glucose was in the clinically recommended range (3.9-10 mmol/L, 70-180 mg/dL). CONCLUSION: Transition to AHCL therapy positively impacted diabetes management in adolescents and youth with chronically elevated glucose levels. It appears to create a window of opportunity in which youth may re-engage with diabetes management. Pseudo-hypoglycaemia can occur during the transition to AHCL. This could be a barrier to AHCL uptake and is likely to require individualised support.

Prevalence and incidence of type 1 diabetes in children aged 0-14 years old in New Zealand in 2021.

AIM: National prevalence and incidence data are important for understanding population trends and allocating health-care resources. We aimed to provide a current national snapshot of prevalence and annual incidence rates for children aged 0-14 with type 1 diabetes (T1D) in Aotearoa New Zealand and to identify differences associated with demographic variables. METHODS: Paediatric diabetes centres across Aotearoa were invited to record anonymised demographic and diabetes data on children under their services between 1 October 2020 and 30 September 2021. National prevalence and incidence were calculated using usually resident population counts from the 2018 census. The effect of ethnicity on prevalence and incidence was assessed using Poisson regression. RESULTS: There were 1209 children aged 0-14 with T1D in October 2021. The national prevalence was 131/100 000 (95% confidence interval (CI) 124-139). European children had twice the prevalence as those of Maori or Pacific ethnicity (P < 0.001). There was no effect by gender (P = 0.3) and prevalence predictably increased with age. The annualised incidence of T1D was 23/100 000 (95% CI 20-26). European children were 2.6 times as likely as Maori children to be diagnosed with T1D in that year (incidence rate ratio = 2.6, 95% CI 1.7-4.2). Regional differences in prevalence and incidence were noted, potentially due to the ethnicity differences across regions. Unadjusted prevalence and incidence decreased with lower socio-economic status, likely due to an over-representation of non-Europeans living in the most deprived areas. CONCLUSIONS: T1D affects an ethnically diverse population in Aotearoa and important regional differences exist that may impact workforce planning.

Use of intermittently scanned continuous glucose monitoring in young people with high-risk type 1 diabetes-Extension phase outcomes following a 6-month randomized control trial.

AIMS: To describe the impact of a 12-month intervention using intermittently scanned continuous glucose monitoring (isCGM) on glycaemic control and glucose test frequency in adolescents and young adults with type 1 diabetes (T1D) and high-risk glycaemic control (HbA1c ≥75 mmol/mol [≥9.0%]). METHODS: In total, 64 young people (aged 13-20 years, 16.6 ± 2.1 years; 48% female; 41% Maori or Pacific ethnicity; mean diabetes duration 7.5 ± 3.8 years) with T1D were enrolled in a 6-month, randomized, parallel-group study comparing glycaemic outcomes from the isCGM intervention (n = 33) to self monitoring blood glucose (SMBG) controls (n = 31). In this 6-month extension phase, both groups received isCGM; HbA1c , glucose time-in-range (TIR), and combined glucose test frequency were assessed at 9 and 12 months. RESULTS: At 12 months, the mean difference in HbA1c from baseline was -4 mmol/mol [-0.4%] (95% confidence interval, CI: -8, 1 mmol/mol [-0.8, 0.1%]; p = 0.14) in the isCGM intervention group, and -7 mmol/mol [-0.7%] (95% CI: -16, 1 mmol/mol [-1.5, 0.1%]; p = 0.08) in the SMBG control group. No participants achieved ≥70% glucose TIR (3.9-10.0 mmol/L). The isCGM intervention group mean rate of daily glucose testing was highest at 9 months, 2.4 times baseline rates (p < 0.001), then returned to baseline by 12 months (incidence rate ratio = 1.4; 95% CI: 0.9, 2.1; p = 0.091). CONCLUSIONS: The use of isCGM in young people with high-risk T1D resulted in transient improvements in HbA1c and glucose monitoring over a 9-month time frame; however, benefits were not sustained to 12 months.

Parental experiences of short term supported use of a do-it-yourself continuous glucose monitor (DIYrtCGM): A qualitative study.

AIMS: To investigate the experiences of parents caring for young children with type 1 diabetes type 1 diabetes using a do-it-yourself continuous glucose monitor (DIYrtCGM) in a supported setting. METHODS: Exit interviews were conducted with parents from 11 families at the end of the MiaoMiao study: a randomised cross-over trial focusing on parental fear of hypoglycaemia. Technical support was provided to participants while using DIYrtCGM during the trial. A convenience sampling approach was used to recruit parents. An in-depth, semi-structured interview approach was used. Thematic analysis was used to identify key themes and subthemes. RESULTS: Parents identified that remote monitoring enabled proactive management and that overall alarms/glucose alerts were useful. Some parents reported reductions in anxiety, increased independence for their child, and improvements in the child-parent relationship. However, parents also reported regular signal loss with DIYrtCGM, along with complicated apps and challenges troubleshooting technical problems. Despite this, nine of the 11 families continued to use the system after the end of the trial. CONCLUSIONS: Do-it-yourself continuous glucose monitoring (CGM) was on balance beneficial for the parents interviewed. However, while access to CGM shifted the burden of care experienced by parents, burden did not significantly reduce for all parents, as the improved glycaemic control that they achieved was accompanied with the responsibility for continually monitoring their child's data. Supported use of do-it-yourself CGM may be an achievable, cost-effective option for parents caring for children with type 1 diabetes in countries without funded access to CGM.

The effect of do-it-yourself real-time continuous glucose monitoring on psychological and glycemic variables in children with type 1 diabetes: A randomized crossover trial.

BACKGROUND: Continuous glucose monitoring (CGM) decreases fear of hypoglycemia (FOH) and improves glycemic control among those affected by type 1 diabetes (T1D). No studies to date have examined the impact of using do-it-yourself real-time continuous glucose monitoring (DIY RT-CGM) on psychological and glycemic outcomes. METHODS: Child-parent dyads were recruited for a multicentre randomized crossover trial. Children with T1D were current intermittently scanned CGM (isCGM) users and aged 2-13 years. Families received either 6 weeks of DIY RT-CGM with parental remote monitoring (intervention) or 6 weeks of isCGM plus usual diabetes care (control), followed by a 4-week washout period, then crossed over. The primary outcome was parental FOH. Secondary outcomes were glycemic control using traditional CGM metrics, as well as a range of other psychosocial measures. FINDINGS: Fifty five child-parent dyads were recruited. The child mean age was 9.1 ± 2.8 years. Although, there was no effect on parental FOH, -0.1 (95%CI: -0.3, 0.1, p = 0.4), time-in-range (TIR) (%3.9-10 mmol/L) was significantly higher with DIY RT-CGM over isCGM (54.3% ± 13.7 vs. 48.1% ± 13.6), mean difference, 5.7% (95%CI 1.8, 9.6, p <0.004). There was no difference for time spent in hypoglycemia. Parent diabetes treatment satisfaction was significantly higher following DIY RT-CGM compared to isCGM, mean difference 5.3 (95%CI: 2.3, 8.2, p <0.001). CONCLUSION: The use of DIY RT-CGM versus isCGM did not improve parental FOH; however, TIR and parental satisfaction with diabetes treatment were significantly improved. This suggests in the short term, DIY RT-CGM appears safe and may offer families some clinically important advantages over isCGM.

Youth and non-European ethnicity are associated with increased loss of publicly funded insulin pump access in New Zealand people with type 1 diabetes.

AIMS: Continuous subcutaneous insulin infusion (CSII) has been publicly funded in New Zealand for people living with type 1 diabetes since 2012. The aim of the current study was to investigate the loss of access, once obtained, to public-funded CSII. The frequency and socio-demographics of access, and loss, to CSII spanning the period 2012 to 2018 were examined. METHODS: Nationally held data collections including the New Zealand Virtual Diabetes Register were used to calculate the overall and subgroup proportions using and ceasing CSII. A logistic regression model was used to estimate odds ratios for pump use for the predictor variables (sex, age group, ethnicity and deprivation index) and to calculate odds ratios for pump cessation for the same demographic factors. RESULTS: Once CSII access is obtained, approximately 4% per year cease CSII in a subsequent year. This cessation of publicly funded CSII was not distributed equally among the population, showing over-representation in youth (aged 10-29 years) and non-Europeans, in particular Maori and Pasifika. Compounding this, it remains less likely for people with diabetes to initially access publicly funded CSII in New Zealand if they are non-European and more socio-economically deprived. CONCLUSIONS: In New Zealand, Maori and Pasifika, as well as youth, are over-represented in the cessation of CSII in comparison with Europeans and all other age groups. These groups are also less likely to gain initial access to public funding. Efforts to understand and reduce these disparities are needed, including review of current public funding access criteria.

Impact of high-risk glycemic control on habitual sleep patterns and sleep quality among youth (13-20 years) with type 1 diabetes mellitus compared to controls without diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1D), glycemic control and sleep have a bidirectional relationship, with unhealthy glycemic control impacting sleep, and inadequate sleep impacting diabetes management. Youth are at risk for poor quality sleep; however, little is known about sleep among youth with high-risk glycemic control. OBJECTIVE: To assess differences in habitual sleep timing, duration, and quality among youth with T1D and controls. SUBJECTS: Two-hundred-thirty youth (13-20 years): 64 with T1D (mean age 16.6 ± 2.1 years, 48% female, diabetes duration 7.5 ± 3.8 years, HbA1c 96 ± 18.0 mmol/mol [10.9 ± 1.7%]), and 166 controls (mean age 15.3 ± 1.5, 58% female). METHODS: Comparison of data from two concurrent studies (from the same community) using subjective and objective methods to assess sleep in youth: Pittsburgh Sleep Quality Index evaluating sleep timing and quality; 7-day actigraphy measuring habitual sleep patterns. Regression analyses were used to compare groups. RESULTS: When adjusted for various confounding factors, youth with T1D reported later bedtimes (+36 min; p < 0.05) and shorter sleep duration (-53 min; p < 0.05) than controls, and were more likely to rate subjective sleep duration (OR 3.57; 95% CI 1.41-9.01), efficiency (OR 4.03; 95% CI 1.43-11.40), and quality (OR 2.59; 95% CI 1.16-5.76) as "poor" (p < 0.05). However, objectively measured sleep patterns were similar between the two groups. CONCLUSIONS: Youth with high-risk T1D experience sleep difficulties, with later bedtimes contributing to sleep deficit. Despite a lack of objective differences, they perceive their sleep quality to be worse than peers without diabetes.

Young people with a variation in sex characteristics in Aotearoa/New Zealand: identity, activism and healthcare decision-making.

Young people born with variations in sex characteristics (VSC) or disorders of sex development (DSD) face numerous challenges in navigating issues relating to identity and to their lived and embodied experience. There is limited published research amplifying the voices of young people with a VSC, especially from Aotearoa/New Zealand. This qualitative study provides an up-to-date picture of the lived experience of 10 young people with a VSC in Aotearoa/New Zealand. The research was conducted in collaboration with the advocacy group, Intersex Youth Aotearoa, and explored the level of support provided by health services, peers and advocacy groups in relation to the ways the participants viewed themselves and their bodies, and their health related decision-making. Findings reveal the pressure on young people with a VSC to conform to cultural and societal norms, specifically, heteronormative and traditional constructs of how male and female bodies should look in Aotearoa/NZ society. Such views, often held and perpetuated by health professionals and parents, contributed to complexities surrounding identity, agency and acceptance of difference experienced by these young people. The implications of these findings are discussed, including the need for better psychological and peer support for young people.

Cutaneous adverse events in a randomized controlled trial of flash glucose monitoring among youth with type 1 diabetes mellitus.

BACKGROUND: The literature regarding flash glucose monitoring (FGM)-associated cutaneous adverse events (AE) is limited. OBJECTIVES: This study among youth participating in a 6 month randomized controlled trial aimed to compare cutaneous AE between FGM and self-monitored blood glucose (SMBG) use and evaluate premature FGM sensor loss. METHODS: Patients aged 13 to 20 years with type 1 diabetes were randomized to intervention (FGM and usual care) or control (SMBG and usual care). Participants self-reported cutaneous AEs electronically every 14 days. Reports were analyzed to determine frequency, type, and severity of cutaneous AEs, and evaluate premature sensor loss. RESULTS: Sixty-four participants were recruited; 33 randomized to FGM and 31 to control. In total, 80 cutaneous AEs were reported (40 in each group); however, the proportion of participants experiencing cutaneous AEs was greater in the FGM group compared to control (58% and 23% respectively, P = .004). FGM participants most frequently reported erythema (50% of AEs), while controls most commonly reported skin hardening (60% of AEs). For FGM users, 80.0% of cutaneous AEs were mild, 17.5% moderate, and 2.5% severe. Among controls, 82.5% of cutaneous AEs were mild and 17.5% moderate. One participant ceased using FGM due to recurring cutaneous AEs. Additionally, over 6 months, 82% of FGM participants experienced at least one premature sensor loss, largely unrelated to a cutaneous AE. CONCLUSIONS: Cutaneous FGM-associated AEs are common, and mostly rated as mild. However, the majority of users continued FGM despite cutaneous AEs. Awareness of cutaneous complications and mitigation measures may reduce cutaneous AEs and improve the overall experience of FGM.

Early identification of cardiac autonomic neuropathy using complexity analysis in children with type 1 diabetes.

AIM: In children and adolescents, there are significant limitations to detecting cardiac autonomic neuropathy (CAN), an important contributor to morbidity and mortality in adults with type 1 diabetes (T1D). The analysis of heart rate variability (HRV) is one method available to detect CAN. Some evidence shows traditional linear HRV measures detect abnormalities in youth with T1D. In this study, we aimed to assess whether non-linear complexity analysis of HRV would assist identification of CAN in youth with T1D and to assess contributory factors. METHODS: We studied 19 youth with T1D and 17 healthy controls. Each had an electrocardiogram recorded continuously for 10 min, at a sampling frequency of 1000 Hz. Using Labview software and an algorithm for complexity analysis, along with standard time-domain and spectral analysis, recordings of the electrocardiogram were analysed to detect differences in HRV between groups. RESULTS: Youth with T1D had significantly higher sample entropy than controls (P = 0.015) suggesting increased complexity in HRV, but similar detrended fluctuation analysis (P = 0.68). Youth with T1D also had increased % high frequency power (P = 0.017) and reduced mid-frequency power (P = 0.019) on spectral analysis. There were no differences in heart rate or blood pressure responses to standing, or time-domain analysis of HRV. Within the T1D group, sample entropy correlated strongly with triglycerides (r = 0.76, P = 0.001) and detrended fluctuation analysis correlated strongly with serum potassium (r = -0.86, P < 0.001). CONCLUSIONS: Complexity analysis of HRV, particularly using sample entropy, may aid detection of CAN in youth with T1D.

Effect of 6 months' flash glucose monitoring in adolescents and young adults with type 1 diabetes and suboptimal glycaemic control: managing diabetes in a 'flash' randomised controlled trial protocol.

BACKGROUND: Teenagers and young adults with type 1 diabetes (T1D) experience significant burden managing this serious chronic condition and glycaemic control is at its unhealthiest during this life stage. Flash glucose monitoring (FGM) is a new technology that reduces the burden of glucose monitoring by easily and discreetly displaying glucose information when an interstitial glucose sensor worn on the upper arm is scanned with a handheld reader, as opposed to traditional capillary glucose sampling by finger prick (otherwise known as self-monitored blood glucose, SMBG). The effectiveness of this technology and impacts of its long-term use in youth with pre-existing suboptimal glycaemic control are unknown. This study therefore aims to investigate the effectiveness of FGM in addition to standard care in young people with T1D. METHODS: This is a two phase study programme including a multi-centre randomised, parallel-group study consisting of a 6-month comparison between SMBG and FGM, with an additional 6-month continuation phase. We will enrol adolescents with T1D aged 13-20 years (inclusive), with suboptimal glycaemic control (mean glycated haemoglobin (HbA1c) in past 6 months ≥75 mmol/mol [≥9%]). Participants will be randomly allocated (1:1) to FGM (FreeStyle Libre; intervention group) or to continue SMBG with capillary blood glucose testing (usual care group). All participants will continue other aspects of standard care with the study only providing the FreeStyle Libre. At 6 months, the control group will cross over to the intervention. The primary outcome is the between group difference in changes in HbA1c at 6 months. Additional outcomes include a range of psychosocial and health economic measures as well as FGM acceptability. DISCUSSION: >If improvements are found, this will further encourage steps towards integrating FGM into regular diabetes care for youth with unhealthy glycaemic control, with the expectation it will reduce daily diabetes management burden and improve short- and long-term health outcomes in this high-risk group. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry on 5 March 2018 ( ACTRN12618000320257p ) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1205-5784).

Optimizing the management of hypoglycaemia in individuals with type 2 diabetes: A randomized crossover comparison of a weight-based protocol compared with two fixed-dose glucose regimens.

AIMS: To determine whether an individualized body weight-based glucose treatment in adults with type 2 diabetes (T2DM) is more likely to resolve hypoglycaemia with a single treatment without excessive rebound hyperglycaemia compared to fixed doses of 12 or 30 g of glucose. METHODS: Adults with T2DM were enrolled in a cross-over study. Each episode of hypoglycaemia (capillary glucose <4.0 mmol/L) was randomly assigned to 1 of 3 treatment protocols: 0.3 g glucose/kg body-weight or a fixed dose of either 12 or 30 g glucose, independent of weight. All participants received each treatment in random order for up to 15 hypoglycaemic episodes. Glucose was re-tested 10 minutes after treatment, with a repeat dose if still <4 mmol/L. RESULTS: Mean (SD) age of the 30 participants was 68 (8.1) years, mean weight was 91.5 (16.8) kg and mean HbA1c was 58.7 (9.2) mmol/mol. Among a total of 244 episodes of hypoglycaemia, 10 participants had 15 treatment episodes and 18 participants had fewer than 10 treatment episodes. The odds ratio, adjusted for multiple comparisons, for resolution of hypoglycaemia at 10 minutes, comparing weight-based treatment and 12 g treatment was 3.2 (95% CI, 1.1-9.0), P = .009, comparing 30 g treatment and 12 g treatment was 8.9 (95% CI, 2.2-36.6), P < .001, and comparing weight-based treatment and 30 g treatment was 0.36 (95% CI, 0.08-1.67) P = .10. CONCLUSION: In T2DM, both a weight-based 0.3 g/kg treatment and a fixed 30 g glucose treatment result in higher blood glucose than a 12 g treatment, along with increased probability of resolution of hypoglycaemia after 10 minutes. Both treatments result in an excess of mild rebound hyperglycaemia (>8 mmol/L) at 30 minutes.

Insulin regimens for newly diagnosed children with type 1 diabetes mellitus in Australia and New Zealand: A survey of current practice.

AIM: There is no consensus on the optimal insulin treatment for children newly diagnosed with type 1 diabetes mellitus (T1DM). The aims of this study were (i) to describe the insulin regimens used at diagnosis by patient age and geographical region and (ii) to explore differences between and within Australia (AU) and New Zealand (NZ) with regards to other aspects of patient management and education. METHODS: An online survey of medical professionals caring for children with T1DM in AU and NZ was undertaken. Questions included clinic demographics, insulin regimen/dosing choices and patient education. RESULTS: Of 110 clinicians identified, 100 responded (91%). The majority of those in AU (69%, P < 0.0001) favour multiple daily injections (MDI) for all ages. In NZ, for patients < 10 years old, (twice daily (BD)) BD therapy was favoured (75%, P < 0.0001), with MDI dominant for ages ≥ 10 years (82%, P < 0.0001). Insulin pump therapy was never considered at diagnosis in NZ, but 38% of clinicians in AU considered using pumps at diagnosis in patients <2 years, but rarely in patients aged 2 and over (16%). Differences in clinician choices were also seen in relation to starting insulin dose. CONCLUSION: This is the first study to examine current clinical practice with regards to children newly diagnosed with T1DM. Practice varies across Australasia by clinician and region. This lack of consensus is likely driven by ongoing debates in the current paediatric diabetes evidence base as well as by differences in clinician/centre preference, variations in resourcing and their interpretations of the influence of various patient factors.

A NOS3 polymorphism determines endothelial response to folate in children with type 1 diabetes or obesity.

OBJECTIVE: To determine the effect of polymorphisms in NOS3 and folate pathway enzymes on vascular function and folate status and endothelial response to folate in children with diabetes or obesity. STUDY DESIGN: A total of 244 subjects (age 13.8 ± 2.8 years, 125 males) were studied for NOS3 and/or folate pathway polymorphisms using polymerase chain reaction/restriction fragment length polymorphism, including at baseline: 139 with type 1 diabetes; 58 with obesity; and 47 controls. The effect of NOS3 genotype on endothelial response to folate (5 mg) was assessed in 85 subjects with diabetes and 28 obese subjects who received active treatment during intervention trials. Vascular function (flow-mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation), clinical, and biochemical measurements were assessed at baseline and 8 weeks in folate intervention studies. RESULTS: Folate pathway enzyme and NOS3 polymorphisms did not significantly affect baseline vascular function. The polymorphism in intron 4 of endothelial nitric oxide synthase altered endothelial response to folate significantly: in subjects with diabetes FMD improved by 6.4 ± 5% (insertion carriers) vs 2.3 ± 6.6% (deletion carriers), P = .01; in obese subjects FMD improved by 1.8 ± 5.4% (insertion carriers) and deteriorated by -3.2 ± 7.2% (deletion carriers), P = .05. More subjects carrying the insertion normalized FMD after folate supplementation (insertion 64% vs deletion 28%, χ(2) = 10.14, P = .001). CONCLUSIONS: A NOS3 polymorphism predicts endothelial response to folate in children with diabetes or obesity, with implications for vascular risk and folate intervention studies.

Emergent inequity of glycaemic metrics for Maori children with type 1 diabetes is negated by early use of continuous glucose monitoring.

AIM: We investigated if continuous glucose monitoring (CGM) in children with type 1 diabetes (T1D) within 12 months of being diagnosed modifies the development of glycaemic outcome inequity on the basis of either ethnicity or socio-economic status (SES). METHOD: De-identified clinical and SES data from the KIWIDIAB data network were collected 12 months after diagnosis in children under 15 years diagnosed with T1D between 1 October 2020 and 1 October 2021. RESULTS: There were 206 children with new onset T1D: CGM use was 56.7% for Maori and 77.2% for Europeans. Mean (SD) HbA1c was 62.4 (14.2) mmol/mol at 12 months post diagnosis, but Maori were 9.4mmol/mol higher compared to Europeans (p<0.001). For those without CGM, Maori had an HbA1c 10.8 (95% CI 2.3 to 19.4, p=0.013) mmol/mol higher than Europeans, whereas there was no evidence of a difference between Maori and Europeans using CGM (62.1 [9.3] mmol/mol vs 58.5 [12.4] mmol/mol p=0.53 respectively). Comparing quintiles of SES, HbA1c was 10.8 (95% CI 4.7 to 16.9, p<0.001) mmol/mol higher in the lowest quintile of SES compared to the highest. CONCLUSION: These observational data suggest CGM use ameliorates the ethnic disparity in HbA1c at 12 months in new onset T1D.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452). Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c.

BACKGROUND: Automated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels. METHODS: In this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non--automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks. RESULTS: A total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, -2.5 percentage points; 95% confidence interval [CI], -3.1 to -1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group. CONCLUSIONS: In this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.).

Nocturnal sleep measured by actigraphy in children with Prader-Willi syndrome.

OBJECTIVE: To assess nocturnal sleep duration by actigraphy in children with Prader-Willi syndrome (PWS). STUDY DESIGN: Baseline measurements including height, weight, and body mass index (BMI) were collected on 8 children with PWS (6 boys) with each subject age- and sex-matched to 2 control children. From 7 consecutive nights of actigraphy data, values for total sleep time (TST), sleep efficiency, sleep latency (SL), number of awakenings after sleep onset, and duration of awakenings after sleep onset (WASO) were extracted. Parents also completed a sleep diary and questionnaire during this period. RESULTS: Subjects with PWS ranged from 4.2 to 15.4 years, and they had a lower height z score and higher BMI z score compared with controls. The PWS group had a shorter SL (P = .0007), longer WASO (P = .009), and higher daytime sleepiness score. TST, sleep efficiency, and number of awakenings after sleep onset were not significantly different between the groups, and subjects with PWS did not wake earlier than controls. There was no correlation between WASO and BMI or between WASO and sleepiness score. CONCLUSION: Children with PWS appear to have a shorter SL but more time awake in the night than normal children and have similar TST and morning wake time compared with controls.

Folate fortification and supplementation do not provide vascular health benefits in type 1 diabetes.

OBJECTIVE: To evaluate the lowest effective dose-response of folic acid on endothelial function in children with type 1 diabetes. STUDY DESIGN: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 20 children with type 1 diabetes (age range 10-18 years) after mandatory folate fortification in Australia. Each child received orally 4 interventions (1 per month)-3 folic acid doses (0.5, 2, and 5 mg) and 1 placebo dose--in random order. The primary outcome was 2-hour postintervention change in endothelial function measured with flow-mediated dilatation (FMD). Thirty-five children with type 1 diabetes from our folic acid interventional trial before folate fortification were used for comparison. RESULTS: All children completed the study. There were no differences in baseline FMD or folate status between the visits. Folic acid supplementation increased serum folate (P = .0001) and red cell folate (P < .0001), but none of the doses improved FMD (P = .96). Baseline serum folate and red cell folate levels and FMD and glyceryl trinitrate-mediated dilatation were significantly higher in these children compared with children from our trial before mandatory folate fortification (P = .0001, .0001, .014, and .04, respectively). CONCLUSIONS: Folate status and vascular function have improved in children with type 1 diabetes since the introduction of mandatory folate fortification, but the beneficial endothelial effects of additional folic acid are no longer present.