Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up.

AIMS: Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up. METHODS: RCT of youth aged 7-15 years with T1D, at two tertiary paediatric centres. Participants were randomised to commence CSII or continue multiple daily injections (MDI). Behaviour, mood, cognition and HbA1c were assessed. Primary outcome was difference in parent-reported behaviour (BASC-2) at 4 months. After the 4-month RCT, MDI participants commenced CSII; outcomes were reassessed at +2 years. RESULTS: Participating youth (n=101) were randomised to CSII (n=56) or MDI (n=45). Significant differences favouring CSII were found at 4 months in parent-reported behaviour problems (Cohen's d 0.41 (95% CI 0.004 to 0.795); p=0.048) and HbA1c (mean (95% CI) difference: 7 (2.3 to 11.7) mmol/mol (0.6% (0.2 to 1.0%); p=0.001)). Improvements from baseline were documented in mood and cognitive outcomes in both study groups over the 4-month RCT; however, no between-group differences were evident at 4 months. Sixteen of 76 (21%) participants completing assessments at +2 years had discontinued CSII. In n=60 still using CSII, measurements of behaviour, mood and HbA1c were comparable to baseline. CONCLUSIONS: Parent-reported behaviour problems and HbA1c, but not mood or neurocognitive outcomes, were clinically significantly lower with CSII, relative to MDI, after 4 months. Observational follow-up indicated no impact of treatment modality at +2 years, relative to baseline levels. Taken together, these data indicate that use of CSII alone does not comprehensively benefit neuropsychological outcomes in childhood T1D.

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.

Developmental Pathway Choices of Young People Presenting to a Gender Service with Gender Distress: A Prospective Follow-Up Study.

This prospective case-cohort study examines the developmental pathway choices of 79 young people (13.25-23.75 years old; 33 biological males and 46 biological females) referred to a tertiary care hospital's Department of Psychological Medicine (December 2013-November 2018, at ages 8.42-15.92 years) for diagnostic assessment for gender dysphoria (GD) and for potential gender-affirming medical interventions. All of the young people had attended a screening medical assessment (including puberty staging) by paediatricians. The Psychological Medicine assessment (individual and family) yielded a formal DSM-5 diagnosis of GD in 66 of the young people. Of the 13 not meeting DSM-5 criteria, two obtained a GD diagnosis at a later time. This yielded 68 young people (68/79; 86.1%) with formal diagnoses of GD who were potentially eligible for gender-affirming medical interventions and 11 young people (11/79; 13.9%) who were not. Follow-up took place between November 2022 and January 2023. Within the GD subgroup (n = 68) (with two lost to follow-up), six had desisted (desistance rate of 9.1%; 6/66), and 60 had persisted on a GD (transgender) pathway (persistence rate of 90.9%; 60/66). Within the cohort as a whole (with two lost to follow-up), the overall persistence rate was 77.9% (60/77), and overall desistance rate for gender-related distress was 22.1% (17/77). Ongoing mental health concerns were reported by 44/50 (88.0%), and educational/occupational outcomes varied widely. The study highlights the importance of careful screening, comprehensive biopsychosocial (including family) assessment, and holistic therapeutic support. Even in highly screened samples of children and adolescents seeking a GD diagnosis and gender-affirming medical care, outcome pathways follow a diverse range of possibilities.

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.

Effect of a Hybrid Closed-Loop System on Glycemic and Psychosocial Outcomes in Children and Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Hybrid closed-loop (HCL) therapy has improved glycemic control in children and adolescents with type 1 diabetes; however, the efficacy of HCL on glycemic and psychosocial outcomes has not yet been established in a long-term randomized clinical trial. Objective: To determine the percentage of time spent in the target glucose range using HCL vs current conventional therapies of continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring (CGM). Design, Setting, and Participants: This 6-month, multicenter, randomized clinical trial included 172 children and adolescents with type 1 diabetes; patients were recruited between April 18, 2017, and October 4, 2019, in Australia. Data were analyzed from July 25, 2020, to February 26, 2021. Interventions: Eligible participants were randomly assigned to either the control group for conventional therapy (continuous subcutaneous insulin infusion or multiple daily insulin injections with or without CGM) or the intervention group for HCL therapy. Main Outcomes and Measures: The primary outcome was the percentage of time in range (TIR) within a glucose range of 70 to 180 mg/dL, measured by 3-week masked CGM collected at the end of the study in both groups. Secondary outcomes included CGM metrics for hypoglycemia, hyperglycemia, and glycemic variability and psychosocial measures collected by validated questionnaires. Results: A total of 135 patients (mean [SD] age, 15.3 [3.1] years; 76 girls [56%]) were included, with 68 randomized to the control group and 67 to the HCL group. Patients had a mean (SD) diabetes duration of 7.7 (4.3) years and mean hemoglobin A1c of 64 (11) mmol/mol, with 110 participants (81%) receiving continuous subcutaneous insulin infusion and 72 (53%) receiving CGM. In the intention-to-treat analyses, TIR increased from a mean (SD) of 53.1% (13.0%) at baseline to 62.5% (12.0%) at the end of the study in the HCL group and from 54.6% (12.5%) to 56.1% (12.2%) in the control group, with a mean adjusted difference between the 2 groups of 6.7% (95% CI, 2.7%-10.8%; P = .002). Hybrid closed-loop therapy also reduced the time that patients spent in a hypoglycemic (<70 mg/dL) range (difference, -1.9%; 95% CI, -2.5% to -1.3%) and improved glycemic variability (coefficient of variation difference, -5.7%; 95% CI, -10.2% to -0.9%). Hybrid closed-loop therapy was associated with improved diabetes-specific quality of life (difference, 4.4 points; 95% CI, 0.4-8.4 points), with no change in diabetes distress. There were no episodes of severe hypoglycemia or diabetic ketoacidosis in either group. Conclusions and Relevance: In this randomized clinical trial, 6 months of HCL therapy significantly improved glycemic control and quality of life compared with conventional therapy in children and adolescents with type 1 diabetes. Trial Registration: ANZCTR identifier: ACTRN12616000753459.

Investigating paediatric hypoglycaemia: Dynamic studies at a tertiary paediatric hospital.

AIM: Paediatric hypoglycaemia often requires specific investigations to determine aetiology. Samples from the time of hypoglycaemia may not be available and a diagnostic fasting test may be required. Additionally, fasting studies can determine safe fasting intervals and prolonged oral glucose challenges can assess hypoglycaemia due to abnormal post-prandial glucose handling. This audit reviewed the current utility and yield of fasting studies, prolonged oral glucose challenges and starch loads. METHODS: Retrospective audit of clinical record to determine purpose and outcome of tests performed at a Tertiary Paediatric Endocrine/Metabolic Testing Unit in Sydney, Australia, from 2013 to 2018 inclusive. RESULTS: One hundred and thirty-eight children (aged 3 weeks-17 years) underwent 170 tests: 122 fasting studies, 20 five-hour OGTTs, 22 uncooked corn starch loads and six modified waxy maize starch (Glycosade) loads. The majority were for diagnostic purposes (n = 113, 66%), with 57 (34%) to guide management in patients with known diagnoses. Following diagnostic studies, 35 (31%) patients received a pathological diagnosis, the most common of which (n = 19, 17%) was accelerated starvation. Hypoglycaemia developed in n = 15/113 (13%) during the diagnostic studies. Management studies helped determine length of safe fast, adjustment of medication or diet and document resolution of pathology. CONCLUSION: Fasting studies remain a safe and effective method to assist with diagnoses, confirm or exclude pathological causes of childhood hypoglycaemia and to guide management of known diagnoses in the paediatric population.

Effect of frequency of sensor use on glycaemic control in individuals on sensor-augmented pump therapy with and without Predictive Low Glucose Management System.

Improved frequency of sensor use improves glycaemic control. Furthermore, there is no deterioration of glycaemic control with increased sensor use in individuals on Predictive Low Glucose Management (PLGM) system. Younger children are more likely to have better sensor uptake than older children.

Positive impacts of changes to a tertiary hospital after-hours endocrine and diabetes on-call service.

AIM: To examine the impact of changes to the endocrine/diabetes after-hours service model of care at a major tertiary children's hospital in Australia. The model aimed to enhance the independence of families and reduce dependency on after-hours calls to health professionals. METHODS: The after-hours activity was captured prospectively using an iPad with a customised FileMaker database. Data were collected for 9 months prior to and for 8 months after the implementation of a modified model of service. Questionnaires gathered information from endocrine junior medical officers (JMOs) and other hospital staff. Data on emergency department visits were analysed for presentations before and after the implementation of the service changes. RESULTS: Changes to the after-hours service resulted in a significant reduction in median calls from 9 (range 0-39) to 2 (range 0-7) per shift. The number of shifts with no calls increased from 2 to 24% and the number of shifts with <3 calls increased from 8 to 60%. Disturbed nights (calls between 10 pm and 6 am) decreased from 75 to 29%. Junior medical officer experience was positive and there was no perceivable increase in workload from in-hospital staff. The number of endocrine patients presenting to the emergency department did not change significantly following the implementation of the new after-hours service. CONCLUSION: This is the only Australian study to prospectively gather accurate on-call data in order to elucidate the impact of changing a hospital's after-hours endocrine/diabetes service to a model that enhanced family empowerment and independence. Historical 24-h on-call service models are not indispensable, and changes can improve sustainability without compromising patient care.

Attachment Patterns in Children and Adolescents With Gender Dysphoria.

The current study examines patterns of attachment/self-protective strategies and rates of unresolved loss/trauma in children and adolescents presenting to a multidisciplinary gender service. Fifty-seven children and adolescents (8.42-15.92 years; 24 birth-assigned males and 33 birth-assigned females) presenting with gender dysphoria participated in structured attachment interviews coded using dynamic-maturational model (DMM) discourse analysis. The children with gender dysphoria were compared to age- and sex-matched children from the community (non-clinical group) and a group of school-age children with mixed psychiatric disorders (mixed psychiatric group). Information about adverse childhood experiences (ACEs), mental health diagnoses, and global level of functioning was also collected. In contrast to children in the non-clinical group, who were classified primarily into the normative attachment patterns (A1-2, B1-5, and C1-2) and who had low rates of unresolved loss/trauma, children with gender dysphoria were mostly classified into the high-risk attachment patterns (A3-4, A5-6, C3-4, C5-6, and A/C) (χ2 = 52.66; p < 0.001) and had a high rate of unresolved loss/trauma (χ2 = 18.64; p < 0.001). Comorbid psychiatric diagnoses (n = 50; 87.7%) and a history of self-harm, suicidal ideation, or symptoms of distress were also common. Global level of functioning was impaired (range 25-95/100; mean = 54.88; SD = 15.40; median = 55.00). There were no differences between children with gender dysphoria and children with mixed psychiatric disorders on attachment patterns (χ2 = 2.43; p = 0.30) and rates of unresolved loss and trauma (χ2 = 0.70; p = 0.40). Post hoc analyses showed that lower SES, family constellation (a non-traditional family unit), ACEs-including maltreatment (physical abuse, sexual abuse, emotional abuse, neglect, and exposure to domestic violence)-increased the likelihood of the child being classified into a high risk attachment pattern. Akin to children with other forms of psychological distress, children with gender dysphoria present in the context of multiple interacting risk factors that include at-risk attachment, unresolved loss/trauma, family conflict and loss of family cohesion, and exposure to multiple ACEs.

Requirements for improving health and well-being of children with Prader-Willi syndrome and their families.

Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families.

Characteristics of Automated Insulin Suspension and Glucose Responses with the Predictive Low-Glucose Management System.

BACKGROUND: The Predictive Low-Glucose Management (PLGM) system suspends basal insulin when hypoglycemia is predicted and reduces hypoglycemia. The aim of this analysis was to explore the characteristics of automated insulin suspension and sensor glucose (SG) responses following PLGM-initiated pump suspension. RESEARCH DESIGN AND METHODS: Children and adolescents with type 1 diabetes used the Medtronic MiniMed™ 640G pump as part of a randomized controlled trial. Data collected on a subgroup of participants on PLGM (suspend before low enabled) from CareLink® Therapy Management Software were analyzed to explore the time and duration of PLGM-initiated pump suspension. Day and nighttime were defined as 06:00 am to 10:00 pm and 10:00 pm to 6:00 am, respectively. RESULTS: There were 20,183 suspend before low events in 8523 days (2.37 events/day). The mean suspend duration was 55.0 ± 32.7 min (day 50.0 ± 30.1, night 71.7 ± 35.1; P < 0.001). Although a 2-h pump suspension was more frequent at night (day 5%, night 18%), a patient-initiated resumption occurred more during day (day 34%, night 12%). SG values did not reach <3.5 and <3 mmol/L in 79% and 91% of the events, respectively. The 2-h SG following pump resumption was higher following autoresumption during the day (day vs. night 9.3 mmol/L vs. 8.4 mmol/L; P < 0.001). CONCLUSIONS: Longer suspends and fewer glycemic excursions occur at night compared with day. The higher glycemic daytime excursions could be due to carbohydrate consumption to increase glucose levels and highlights the need for health care professionals to educate patients about carbohydrate intake around pump suspension.

Reduction in Hypoglycemia With the Predictive Low-Glucose Management System: A Long-term Randomized Controlled Trial in Adolescents With Type 1 Diabetes.

OBJECTIVE: Short-term studies with automated systems that suspend basal insulin when hypoglycemia is predicted have shown a reduction in hypoglycemia; however, efficacy and safety have not been established in long-term trials. RESEARCH DESIGN AND METHODS: We conducted a 6-month, multicenter, randomized controlled trial in children and adolescents with type 1 diabetes using the Medtronic MiniMed 640G pump with Suspend before low (predictive low-glucose management [PLGM]) compared with sensor-augmented pump therapy (SAPT) alone. The primary outcome was percentage time in hypoglycemia with sensor glucose (SG) <3.5 mmol/L (63 mg/dL). RESULTS: In an intent-to-treat analysis of 154 subjects, 74 subjects were randomized to SAPT and 80 subjects to PLGM. At baseline, the time with SG <3.5 mmol/L was 3.0% and 2.8% in the SAPT and PLGM groups, respectively. During the study, PLGM was associated with a reduction in hypoglycemia compared with SAPT (% time SG <3.5 mmol/L: SAPT vs. PLGM, 2.6 vs. 1.5, P < 0.0001). A similar effect was also noted in time with SG <3 mmol/L (P < 0.0001). This reduction was seen both during day and night (P < 0.0001). Hypoglycemic events (SG <3.5 mmol/L for >20 min) also declined with PLGM (SAPT vs. PLGM: events/patient-year 227 vs. 139, P < 0.001). There was no difference in glycated hemoglobin (HbA1c) at 6 months (SAPT 7.6 ± 1.0% vs. PLGM 7.8 ± 0.8%, P = 0.35). No change in quality of life measures was reported by participants/parents in either group. There were no PLGM-related serious adverse events. CONCLUSIONS: In children and adolescents with type 1 diabetes, PLGM reduced hypoglycemia without deterioration in glycemic control.

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.

Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced Hypoglycemia in Type 1 Diabetes.

BACKGROUND: Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions. METHODS: This was a randomized, controlled cross-over study in which 25 participants performed 2 consecutive sessions of 30 min of moderate-intensity exercise while on basal continuous subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and an intervention day with SAPT and PLGM. The predictive algorithm suspended basal insulin when sensor glucose was predicted to be below the preset hypoglycemic threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. RESULTS: Results were analyzed in 19 participants. In the intervention arm with both thresholds, only 6 participants (32%) required treatment for hypoglycemia compared with 17 participants (89%) in the control arm (P = 0.003). In participants with a 2-h pump suspension on intervention days, the plasma glucose was 84 ± 12 and 99 ± 24 mg/dL at thresholds of 70 and 80 mg/dL, respectively. CONCLUSIONS: SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.

Prevention of Insulin-Induced Hypoglycemia in Type 1 Diabetes with Predictive Low Glucose Management System.

BACKGROUND: Sensor-augmented pump therapy (SAPT) with algorithms to predict impending low blood glucose and suspend insulin delivery has the potential to reduce hypoglycemia exposure. The aim of this study was to determine whether predictive low glucose management (PLGM) system is effective in preventing insulin-induced hypoglycemia in controlled experiments. METHODS: Two protocols were used to induce hypoglycemia in an in-clinic environment. (A) Insulin bolus: Insulin was administered as a manual bolus through the pump. (B) Increased basal insulin: Hypoglycemia was induced by increasing basal rates overnight to 180%. For both protocols, participants were randomized and studied on 2 separate days; a control day with SAPT alone and an intervention day with SAPT and PLGM activated. The predictive algorithm was programmed to suspend basal insulin infusion when sensor glucose was predicted to be <80 mg/dL in 30 min. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. RESULTS: With insulin bolus, 24/28 participants required hypoglycemia treatment with SAPT alone compared to 5/28 participants when PLGM was activated (P ≤ 0.001). With increased basal rates, all the eight SAPT-alone participants required treatment for hypoglycemia compared to only one with SAPT and PLGM. There was no post pump-suspend hyperglycemia with insulin bolus (P = 0.4) or increased basal rates (P = 0.69) in participants with 2-h pump suspension on intervention days. CONCLUSIONS: SAPT with PLGM reduced the requirement for hypoglycemia treatment following insulin-induced hypoglycemia in an in-clinic setting.

Utility of salivary enzyme immunoassays for measuring estradiol and testosterone in adolescents: a pilot study.

AIM: We investigated the utility of enzyme immunoassay kits for measuring low levels of salivary estradiol and testosterone in adolescents and objectively assessed prevalence of blood contamination. METHODS: Endocrine patients provided plasma and saliva for estradiol (females) or testosterone (males) assay. Saliva samples were also tested with a blood contamination kit. RESULTS: Picomolar levels of salivary estradiol in females failed to show any significant correlation with plasma values (r=0.20, p=0.37). The nanomolar levels of salivary testosterone in males showed a strong correlation (r=0.78, p<0.001). A significant number of saliva samples had blood contamination. After exclusion, correlations remained non-significant for estradiol, but strengthened for testosterone (r=0.88, p<0.001). CONCLUSION: The salivary estradiol enzyme immunoassay is not clinically informative at low levels. Users should interpret clinical saliva with caution due to potential blood contamination. Our data supports the utility of the salivary testosterone enzyme immunoassay for monitoring adolescent boys on hormone developmental therapy.

Improved insulin sensitivity and body composition, irrespective of macronutrient intake, after a 12 month intervention in adolescents with pre-diabetes; RESIST a randomised control trial.

BACKGROUND: A higher protein to carbohydrate ratio in the diet may potentiate weight loss, improve body composition and cardiometabolic risk, including glucose homeostasis in adults. The aim of this randomised control trial was to determine the efficacy of two structured lifestyle interventions, differing in dietary macronutrient content, on insulin sensitivity and body composition in adolescents. We hypothesised that a moderate-carbohydrate (40-45% of energy), increased-protein (25-30%) diet would be more effective than a high-carbohydrate diet (55-60%), moderate-protein (15%) diet in improving outcomes in obese, insulin resistant adolescents. METHODS: Obese 10-17 year olds with either pre-diabetes and/or clinical features of insulin resistance were recruited at two hospitals in Sydney, Australia. At baseline adolescents were prescribed metformin and randomised to one of two energy restricted diets. The intervention included regular contact with the dietician and a supervised physical activity program. Outcomes included insulin sensitivity index measured by an oral glucose tolerance test and body composition measured by dual-energy x-ray absorptiometry at 12 months. RESULTS: Of the 111 adolescents recruited, 85 (77%) completed the intervention. BMI expressed as a percentage of the 95th percentile decreased by 6.8% [95% CI: -8.8 to -4.9], ISI increased by 0.2 [95% CI: 0.06 to 0.39] and percent body fat decreased by 2.4% [95% CI: -3.4 to -1.3]. There were no significant differences in outcomes between diet groups at any time. CONCLUSION: When treated with metformin and an exercise program, a structured, reduced energy diet, which is either high-carbohydrate or moderate-carbohydrate with increased-protein, can achieve clinically significant improvements in obese adolescents at risk of type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trail Registry ACTRN12608000416392 . Registered 25 August 2008.

Insulin pump-associated adverse events in children and adolescents--a prospective study.

BACKGROUND: Intensive insulin regimens are now the mainstay of modern, type 1 diabetes mellitus management. Insulin pumps (CSII) are a key technique used. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events (AEs) and their incidence and characteristics. SUBJECTS AND METHODS: Phone calls to our 24-h diabetes support service were screened for CSII-associated AEs. Phone interviews were conducted with the parent/patient, within 96 h of the event. Interviews explored AE characteristics and the role of the user, as well as questions relating to outcome and the impact to the family and patient. Comparisons were made with clinic CSII patients not reporting an AE. RESULTS: Over a 16-week study period, 50 confirmed AEs occurred in 45 of 405 (11.1%) patients. This was annualized to an AE incidence of 40 AEs/100 person-years. Pump malfunction and infusion set/site failures were the most common events reported, occurring in 27 (54.0%) and 18 (36.0%) AEs, respectively. A user- or education-related issue was implicated in 22 (44.0%) events. Pump replacement occurred in 19 of 50 occurrences (38.0%). Additionally, 16 (32.0%) reported a hospital admission or emergency department attendance as a consequence. When compared with those on CSII not reporting an AE, AEs were associated with age <10 years (odds ratio=3.2 [95% confidence interval, 1.7-6.1]) but not with gender, glycosylated hemoglobin, diabetes duration, or pumping duration. CONCLUSIONS: This is the first prospective study to look at AEs in modern-generation insulin pumps. AEs appear common and should be anticipated. Their origin is multifactorial, with the pump, associated consumables, and the user all being important factors. Ongoing support and anticipatory education are essential to minimize pump-associated AEs and their impact.

Family perceptions of insulin pump adverse events in children and adolescents.

BACKGROUND: Insulin pumps (for continuous subcutaneous insulin infusion [CSII]) are used widely in type 1 diabetes mellitus. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events and no data on family perceptions of adverse events and their confidence in dealing with them. SUBJECTS AND METHODS: We approached all families of children and adolescents ≤ 19 years of age on CSII attending the diabetes clinic over a 16-week clinic cycle. Participants completed a retrospective questionnaire examining issues over the previous 12 months. Data on pump adverse events as well as answers to questions pertaining to education and confidence were collected. RESULTS: Our survey received a response rate of 99%, with 235 of the 238 families approached participating. In the preceding 12 months, 104 of 230 (45%) had reported at least one pump-related adverse event (either mechanical or set-related), with an associated 52 of 229 (23%) resulting in pump replacement. This equated to a minimum incidence density of 53 adverse events/100 person-years. Additionally, 18 of 230 (8%) reported a hospital admission or emergency department attendance as a consequence. Pump malfunction and infusion set/site failures were the most common events reported, with one or more events in 58 of 104 (56%) and 47 of 104 (45%), respectively. Adverse events, excluding set/site failures, were associated with older age (13.1 ± 3.4 years vs. 11.9 ± 4 years; P = 0.02). CONCLUSIONS: This is the first study to look at family perceptions of adverse events while using modern CSII. It highlights a high self-reported rate of CSII-related adverse events, pump replacement, and subsequent presentation to the hospital. Potential areas for additional targeted education are identified. Further prospective study examining pump adverse event characteristics and incidence is warranted.