Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.

AIM: To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. METHODS: In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. RESULTS: When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. CONCLUSION: Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.

Glycaemic outcomes in Australasian children and adults with type 1 diabetes: failure to meet targets across the age spectrum.

BACKGROUND: The goal of therapy in type 1 diabetes (T1D) is to achieve optimal glycaemic targets and reduce complications. Robust data representing glycaemic outcomes across the lifespan are lacking in Australasia. AIMS: To examine contemporary glycaemic outcomes and rate of use of diabetes technologies in Australasian people with T1D. METHODS: Cross-sectional analysis of de-identified data from 18 diabetes centres maintained in the Australasian Diabetes Data Network registry during 2019. Glycaemia was measured using glycated haemoglobin (HbA1c). The proportion of people with T1D achieving the international HbA1c target of <53 mmol/mol (7%) was calculated. Rates of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were determined. RESULTS: A total of 7988 individuals with T1D with 30 575 visits were recorded in the registry. The median (interquartile range) age was 15.3 (10.0) years and diabetes duration was 5.7 (9.4) years with 49% on multiple daily injections (MDI) and 36% on CSII. The mean HbA1c for the whole cohort was 66 mmol/mol (8.2%). HbA1c increased with age, from 60 mmol/mol (7.6%) in children <10 years, increasing during adolescence and peaking at 73 mmol/mol (8.8%) in the 20-25 years age group. The HbA1c target of <53 mmol/mol (7%) was met in 18% of children and 13% of adults. HbA1c was lower on CSII as compared with those on MDI (P < 0.0001). CONCLUSIONS: Only a minority of children and adults achieve the recommended glycaemic goals despite access to specialist care in major diabetes centres. There is a need to identify factors that improve glycaemic outcomes.

Perspectives of culturally and linguistically diverse families in the management of children with type 1 diabetes in Western Australia.

OBJECTIVES: Children with Type 1 diabetes (T1D) from different ethnic backgrounds are growing in proportion in clinical practice and tend to have a higher risk of poor health outcomes. The study aimed to investigate the perspectives of culturally and linguistically diverse families in the management of children with T1D in Western Australia. DESIGN: A generic qualitative approach was used. Families of children and adolescents with T1D with first-generation African, Asian or Middle Eastern background were invited to participate in a semi-structured interview. The interviews were audio-recorded, transcribed and analysed thematically. Demographic, clinical and socio-economic data were collected from all participants. RESULTS: Fifteen families (27% African, 33% Middle Eastern, 40% Asian) participated in the study. The mean (SD) age of the child with T1D was 10.2 (5.1) years, had diabetes for 2.9 (1.6) years and an average HbA1c of 67 (15) mmol/mol. Four main themes were identified through qualitative analysis. 'Dietary challenges': lack of adequate food resources posed a barrier to determine carbohydrate amount in traditional meals; 'Linguistic challenges': inadequate reading and language skills affected comprehension of written information and the desire for pictorial resources was reported; 'Limited Support': absence of extended family made management of T1D difficult; and 'Knowledge': a key facilitator, which was acquired through clinic education, enabled families to develop skills to effectively manage T1D. CONCLUSION: The study highlights the need to consider cultural diversity, psychosocial needs, English proficiency and health literacy when assessing and planning diabetes education. These findings will be useful to formulate a more culturally sensitive approach to diabetes education to improve care and outcomes for young people with T1D from culturally and linguistically diverse families.

Hybrid closed-loop therapy with a first-generation system increases confidence and independence in diabetes management in youth with type 1 diabetes.

AIM: Hybrid closed-loop (HCL) therapy improves glycaemic control in adolescents with type 1 diabetes; however, little is known about their lived experience using these systems. The aim of this study was to explore the lived experiences of youth with type 1 diabetes using HCL therapy, and their parents, to provide insight into their lived experiences. METHODS: Adolescents and young adults aged 12-25 years, who used Medtronic MiniMed™ 670G HCL system during a 6-month randomised clinical trial, and their parents, were invited to participate in a semi-structured interview at the end of the study. Open-ended questions were used to explore the lived experiences of families using HCL. The interviews were audio-recorded, transcribed and analysed using thematic analysis to determine the main themes. RESULTS: In all, 17 young people with type 1 diabetes mean ± SD age: 17.5 ± 4.2 years, diabetes duration: 11.0 ± 4.9 years and HbA1c 64 ± 9 mmol/mol (8.0 ± 0.8%) and 10 parents were interviewed. Three themes were identified: (1) 'Developing confidence and trust in the system', (2) 'Reduction in anxiety' and (3) 'Issues with device'. They reported a positive experience using HCL, with improvements in glucose levels and increased independence with diabetes management. However, frustration around the number of alarms and notifications associated with the system were also identified as issues. CONCLUSION: Both youth and parents acknowledged the benefits of this first-generation HCL system in improving glycaemic outcomes and in providing flexibility and independence. These lived experiences provide valuable information in the introduction and provision of targeted education with HCL therapy.

Evaluation of real-life clinical outcomes in Australian youth with type 1 diabetes on hybrid closed-loop therapy: A retrospective study.

AIM: To determine the clinical outcomes and evaluate the perspectives of children with Type 1 diabetes (T1D) and their parents managing their child on hybrid closed-loop (HCL) therapy. METHODS: Children with T1D on HCL attending a tertiary diabetes centre between April 2019 and July 2021 were included. A retrospective analysis of glycaemic data was conducted to determine the clinical outcomes. Time spent in closed loop, time in target glucose range (TIR 3.9-10 mmol/L), hypoglycaemia and hyperglycaemia were collected at baseline, 4 weeks, 3 and 6 months post-HCL. User experience was assessed by questionnaires administered to parents of children with T1D. RESULTS: Seventy-one children, mean (SD) age of 12.2 (3.2) years were commenced on HCL. Ten (14%) discontinued HCL use, with 60% discontinuing within the first 6 months. Glycaemic outcomes were analysed in 52 children. Time spent in closed loop was 78 (21) % at 4 weeks, declined to 69 (28) % at 3 months (P = 0.037) and 63 (34) % at 6 months (P = 0.001). The mean %TIR increased from 59.8 at baseline to 67.6 at 3 months and 65.6 at 6 months with a mean adjusted difference of 7.8% points [95% CI 3.6, 11.9] and 5.5% points [95% CI 1.4, 9.5], respectively. There was a reduction in time > 10 mmol/L and time < 3.9 mmol/L from baseline to 6 months. Although families faced challenges with technology, better glucose control with reduced glycaemic fluctuations were reported. CONCLUSIONS: HCL therapy is associated with improved glycaemia; however, adequate support and education are required for best outcomes.

Utilisation, access and recommendations regarding technologies for people living with type 1 diabetes: consensus statement of the ADS/ADEA/APEG/ADIPS Working Group.

INTRODUCTION: Type 1 diabetes presents significant challenges for optimal management. Despite intensive glycaemic control being the standard of care for several decades, glycaemic targets are infrequently achieved and the burden of complications remains high. Therefore, the advancement of diabetes management technologies has a major role in reducing the clinical and economic impact of the disease on people living with type 1 diabetes and on health care systems. However, a national framework is needed to ensure equitable and sustainable implementation of these technologies as part of holistic care. MAIN RECOMMENDATIONS: This consensus statement considers technologies for insulin delivery, glucose sensing and insulin dose advice that are commercially available in Australia. While international position statements have provided recommendations for technology implementation, the ADS/ADEA/APEG/ADIPS Working Group believes that focus needs to shift from strict trial-based glycaemic criteria towards engagement and individualised management goals that consider the broad spectrum of benefits offered by technologies. CHANGES IN MANAGEMENT AS RESULT OF THIS STATEMENT: This Australian consensus statement from peak national bodies for the management of diabetes across the lifespan outlines a national framework for the optimal implementation of technologies for people with type 1 diabetes. The Working Group highlights issues regarding equity of access to technologies and services, scope of clinical practice, credentialling and accreditation requirements, regulatory issues with "do-it-yourself" technology, national benchmarking, safety reporting, and ongoing patient advocacy.

Reduced prevalence of impaired awareness of hypoglycemia in a population-based clinic sample of youth with type 1 diabetes.

BACKGROUND: Impaired awareness of hypoglycemia (IAH) is associated with an increased risk for severe hypoglycemia (SH). However, reduced rates of SH raise the question as to whether there has been a reduction in IAH. The aim of this study was to determine the change in prevalence of IAH in a population-based cohort of adolescents with Type 1 diabetes (T1D). METHODS: Children older than 12 years with T1D documented their responses to hypoglycemia based on the modified Clarke questionnaire. The prevalence of IAH was also analyzed in a similar population-based cohort using the same questionnaire in 2002. The clinical details of the participants and the number of SH events in the preceding year were determined from the Western Australian diabetes database. RESULTS: The questionnaire was administered to 413 children in 2002 and to 444 children in 2015 with similar baseline characteristics. The prevalence of IAH was 33% in 2002 and 21% in 2015 (P < .001). A lower HbA1c, younger age at diagnosis and longer duration of diabetes correlated with IAH in 2002 but not in 2015. There was a significant decline in the rates of SH in 2015 compared with 2002 (P < .001) despite a reduced HbA1c in 2015. IAH increased the risk of SH in both cohorts (52 vs 16 events/100 patient years in 2002 and 8 vs 2 events/100 patient years in 2015). CONCLUSIONS: Although IAH has reduced, IAH is still prevalent in a substantial minority of adolescents and continues to be associated with an increased risk of SH.

Transient pseudohypoaldosteronism in infancy secondary to urinary tract infection.

AIM: Hyponatraemia with hyperkalaemia in infancy is a typical presentation of congenital adrenal hyperplasia. In the presence of pyelonephritis, the same biochemical picture can occur with transient type 1 pseudohypoaldosteronism (PHA-1) also termed type 4 renal tubular acidosis. Recognition of PHA-1 enables appropriate management thus avoiding unnecessary investigations and treatment. To improve awareness of this condition, we present a case series to highlight the clinical and biochemical features of PHA-1. METHODS: A retrospective chart review of patients diagnosed with transient PHA-1 at a tertiary children's hospital in Western Australia was conducted. RESULTS: Five male infants (32 days to 6 months) with transient PHA-1 were identified. Failure to thrive was the most common symptom with hyponatraemia on presentation. Two infants had antenatally diagnosed bilateral hydronephrosis and urinary tract infection (UTI) on admission. Two infants were treated for congenital adrenal hyperplasia and received hydrocortisone. All infants had UTI and required parenteral antibiotics. The condition was transient and hyponatraemia corrected by day 4 in all infants. There was no correlation between plasma sodium and aldosterone levels. The severity of PHA-1 was independent of the underlying renal anomaly. Four infants had hydronephrosis and vesicoureteric reflux. Surgical intervention was required in two infants. CONCLUSIONS: PHA-1 may be precipitated by UTI or urinary tract anomalies in early infancy. Urine analysis should be performed in infants with hyponatraemia. Diagnosis of PHA-1 facilitates appropriate renal investigations to reduce long-term morbidity.

Report and review of described associations of Mayer-Rokitansky-Küster-Hauser syndrome and Silver-Russell syndrome.

Silver-Russell syndrome (SRS) and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are described in isolation. However, their co-occurrence has only been rarely reported. Here, we present a case report of an adolescent with SRS who was diagnosed with MRKH during the evaluation of primary amenorrhoea. Multiplex ligation-dependent probe amplification analysis showed a normal methylation pattern and normal dosage at 11p15.5. A PubMed search for all peer-reviewed publications (original articles and reviews) using the key words Silver-Russell syndrome, Mayer-Rokitansky-Küster-Hauser syndrome, genetics, hypomethylation and reproductive anomalies identified three cases of SRS with MRKH, two of which were associated with significant hypomethylation of the H19 imprinting control region of the 11p15.5 locus. This report highlights the association between SRS and MRKH. The absence of hypomethylation and normal dosage at 11p15.5 suggests these two rare entities share alternative aetiopathogenic mechanisms.

Clinical Outcomes with MiniMedTM 780G Advanced Hybrid Closed-Loop Therapy in 2- to 6-Year-Old Children with Type 1 Diabetes.

Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

Improved Glycemic Outcomes With Diabetes Technology Use Independent of Socioeconomic Status in Youth With Type 1 Diabetes.

OBJECTIVE: Technology use in type 1 diabetes (T1D) is impacted by socioeconomic status (SES). This analysis explored relationships between SES, glycemic outcomes, and technology use. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of HbA1c data from 2,822 Australian youth with T1D was undertaken. Residential postcodes were used to assign SES based on the Index of Relative Socio-Economic Disadvantage (IRSD). Linear regression models were used to evaluate associations among IRSD quintile, HbA1c, and management regimen. RESULTS: Insulin pump therapy, continuous glucose monitoring, and their concurrent use were associated with lower mean HbA1c across all IRSD quintiles (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA1c (P = 0.624), reflecting a similar association of lower HbA1c with technology use across all IRSD quintiles. CONCLUSIONS: Technology use was associated with lower HbA1c across all socioeconomic backgrounds. Socioeconomic disadvantage does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.

Impact of Body Composition on the Accuracy of a Medtronic Guardian Continuous Glucose Monitoring System.

Continuous glucose monitoring (CGM) systems are used in therapeutic decisions for diabetes management, however, the impact of body composition on CGM accuracy is not known. Body composition variables (body mass index [BMI], midarm circumference, percentage fat, and impedance) were collected in an observational study designed to determine the accuracy of an investigational Medtronic Guardian™ sensor 3. Seven days of sensor glucose data were analyzed from 112 participants >7 years of age with mean BMI Z score 0.48 (<18 years) and BMI 26.7 kg/m2 (≥18 years). The outcome was the absolute relative difference between the sensor and blood glucose readings. Data were analyzed using generalized estimating equations to account for correlation between repeated measures. No statistically significant associations between measures of body composition and device accuracy were found. Body composition does not have a meaningful impact on the accuracy of CGM systems.

Outcomes and experiences of families with children with type 1 diabetes on insulin pumps through subsidised pump access programs in Western Australia.

Introduction: In Australia, access to insulin pump therapy for children with type 1 diabetes (T1D) is predominantly restricted to families with private health insurance. In an attempt to improve equity, additional subsidised pathways exist which provide pumps to families with reduced financial resources. We aimed to describe the outcomes and experiences of families with children commenced on pumps through these subsidised pathways in Western Australia (WA). Methods: Children with T1D in WA who did not have private health insurance and received pumps from the subsidised pump programs between January 2016 and December 2020 were included. Study 1 was designed to review glycaemic outcome. A retrospective analysis of HbA1c was conducted in the whole cohort and in children who commenced pump after the first year of diagnosis to exclude the impact of the partial clinical remission phase following diagnosis. HbA1c at baseline, and six, 12, 18 and 24 months after pump initiation were collected. Study 2 was designed to review experiences of families commenced on pumps through subsidised pathway. A questionnaire designed by the clinical team was distributed to parents via an online secure platform to capture their experiences. Results: Of the 61 children with mean (SD) age 9.0 (4.9) years who commenced pump therapy through subsidised pump programs, 34 children commenced pump therapy after one year of diagnosis of T1D. The median (IQR) HbA1c (%) in 34 children at baseline was 8.3 (1.3), with no statistically significant change from baseline at six months [7.9 (1.4)], 12 months [8.0 (1.5)], 18 months [8.0 (1.3)] or 24 months [8.0 (1.3)]. The questionnaire response rate was 56%. 83% reported intention to continue pump therapy, however 58% of these families did not have avenue to acquire private health insurance. Families expressed inability to procure private health insurance due to low income and unreliable employment and remained largely unsure about the pathway to obtain the next pump. Discussion: Children with T1D who commenced insulin pump therapy on subsidised pathways maintained glycaemic control for two years, and families favored pumps as a management option. However, financial limitations persist as a significant barrier to procure and continue pump therapy. Pathways for access need to be assessed and advocated.

Impact of Missing Data on the Accuracy of Glucose Metrics from Continuous Glucose Monitoring Assessed Over a 2-Week Period.

Objective: To explore the impact of missing data on the accuracy of continuous glucose monitoring (CGM) metrics collected for a 2-week period in a clinical trial. Research Design and Methods: Simulations were conducted to examine the effect of various patterns of missingness on the accuracy of CGM metrics as compared with a "complete" data set. The proportion of missing data, the "block size" in which the data were missing, and the missing mechanism were modified for each "scenario." The degree of agreement between simulated and "true" glycemic measures under each scenario was presented as R2. Results: Under all missing patterns, R2 declined as the proportion of missing data increased, however, as the "block size" of missing data increased, the percentage of missing data had a more pronounced effect on the agreement between measures. For a 14-day CGM data set to be considered representative for percentage time in range (%TIR), at least 70% of CGM data should be available over at least 10 days (R2 > 0.9). Skewed outcome measures, such as percentage time below range and coefficient of variation, were more affected by missing data than the less skewed measures (%TIR, percentage time above range, mean glucose). Conclusions: Both the degree and pattern of missing data impact upon the accuracy of recommended CGM-derived glycemic measures. In planning research, an understanding of patterns of missing data in the study population is required to gauge the likely effects of missing data on outcome accuracy. Trial registration number: Australian New Zealand Clinic Trials Registry ACTRN12616000753459.

Socioeconomic status and diabetes technology use in youth with type 1 diabetes: a comparison of two funding models.

Background: Technology use, including continuous glucose monitoring (CGM) and insulin pump therapy, is associated with improved outcomes in youth with type 1 diabetes (T1D). In 2017 CGM was universally funded for youth with T1D in Australia. In contrast, pump access is primarily accessed through private health insurance, self-funding or philanthropy. The study aim was to investigate the use of diabetes technology across different socioeconomic groups in Australian youth with T1D, in the setting of two contrasting funding models. Methods: A cross-sectional evaluation of 4957 youth with T1D aged <18 years in the national registry was performed to determine technology use. The Index of Relative Socio-Economic Disadvantage (IRSD) derived from Australian census data is an area-based measure of socioeconomic status (SES). Lower quintiles represent greater disadvantage. IRSD based on most recent postcode of residence was used as a marker of SES. A multivariable generalised linear model adjusting for age, diabetes duration, sex, remoteness classification, and location within Australia was used to determine the association between SES and device use. Results: CGM use was lower in IRSD quintile 1 in comparison to quintiles 2 to 5 (p<0.001) where uptake across the quintiles was similar. A higher percentage of pump use was observed in the least disadvantaged IRSD quintiles. Compared to the most disadvantaged quintile 1, pump use progressively increased by 16% (95% CI: 4% to 31%) in quintile 2, 19% (6% to 33%) in quintile 3, 35% (21% to 50%) in quintile 4 and 51% (36% to 67%) in the least disadvantaged quintile 5. Conclusion: In this large national dataset, use of diabetes technologies was found to differ across socioeconomic groups. For nationally subsidised CGM, use was similar across socioeconomic groups with the exception of the most disadvantaged quintile, an important finding requiring further investigation into barriers to CGM use within a nationally subsidised model. User pays funding models for pump therapy result in lower use with socioeconomic disadvantage, highlighting inequities in this funding approach. For the full benefits of diabetes technology to be realised, equitable access to pump therapy needs to be a health policy priority.

Arginine extravasation leading to skin necrosis.

Arginine hydrochloride is used in the evaluation of short stature and in the management of urea cycle disorders. In recent times, it has been used in the treatment of stroke-like episodes of MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes). We want to highlight the need for good intravenous access and monitoring the drip site to prevent extravasation injuries that can be caused by arginine, which is a hyperosmolar solution.