Sydney Diabetes centre's experience of the Australian Government's roll out of subsidised continuous glucose monitoring for children with type 1 diabetes mellitus.

AIM: To determine patient/carer expectations of continuous glucose monitoring (CGM) and short-term satisfaction, to assess the efficacy of CGM in improving: fear of hypoglycaemia and glycaemic control (HbA1c , ketosis, hypoglycaemia) and to determine time requirements of diabetes clinic staff in commencing and administering CGM. METHODS: We assessed CGM-naïve patients starting on CGM at a Sydney Diabetes Centre following the introduction of a nationwide government subsidy for CGM. A standardised questionnaire was administered collecting demographic and glycaemic information in addition to Likert scale assessment of expectations and satisfaction. Clinic staff reported time dedicated to CGM education, commencement and follow-up. RESULTS: A total of 55 patients or parents/carers completed baseline questionnaires, with 37 completing a 3-month follow-up questionnaire. There were high expectations of CGM prior to commencement and high satisfaction ratings on follow-up. CGM improved fear of hypoglycaemia, and total daily insulin dose increased after commencement of CGM. There was a trend towards lower HbA1c that was not statistically significant and no statistically significant reduction in ketosis or hypoglycaemia. Comments were mostly positive, with some concern raised regarding technical issues and a lack of subsidy after 21 years of age. Staff time requirements were substantial, with an estimated average of 7.7 h per patient per year. CONCLUSIONS: Patients and families have high expectations of CGM, and satisfaction levels are high in the short term. Total insulin delivery increased after CGM commencement. Time requirements by staff are substantial but are worthwhile if families' overall satisfaction levels are high.

Single High-Dose Oral Vitamin D3 Therapy (Stoss): A Solution to Vitamin D Deficiency in Children With Inflammatory Bowel Disease?

OBJECTIVES: Vitamin D deficiency is common in children with inflammatory bowel disease (IBD). The aim of this study was to determine the safety and efficacy of stoss therapy on vitamin D levels during a period of 6 months in children with IBD and vitamin D deficiency (<50 nmol/L). METHODS: A retrospective chart review was undertaken, focusing upon children managed in the IBD clinic at Sydney Children's Hospital between 2006 and 2010. Those with a 25-hydroxyvitamin D (25-OHD) level <50 nmol/L and those who received stoss therapy were included in this study. RESULTS: A total of 76 children received stoss therapy. There was a significant and sustained increase in 25-OHD levels at all of the time points compared with baseline (40.8 ±â€Š7.5 nmol/L), 1 month (145.6 ±â€Š51.8 nmol/L), 3 months (87.1 ±â€Š28.4 nmol/L), and 6 months 69.2 ±â€Š31.3 nmol/L). There were no significant changes in serum calcium, phosphate, or parathyroid hormone at any time points. CONCLUSIONS: Stoss therapy safely and effectively achieved and maintained a level of 25-OHD >50 nmol/L during 6 months in these children with IBD. Further prospective studies are now required to confirm this finding and establish whether this intervention has other benefits.

A pilot randomized controlled trial of a post-discharge program to support emerging adults with type 1 diabetes mellitus transition from pediatric to adult care.

AIMS: There is a paucity of randomized controlled trials (RCT) examining transition from pediatric to adult care in type 1 diabetes mellitus (T1DM). This study aimed to determine if transition in T1DM is more effective with a comprehensive transition program (CTP) compared with standard clinical practice (SCP). METHODS: This RCT recruited as young people left pediatric diabetes services. The trial co-ordinator provided CTP participants with standardized telephone communication support at week 1, and 3, 6, and 12 months post-discharge from pediatric care. SCP participants were briefly contacted at 6 and 12 months post-discharge to confirm transfer status; they received no other post-discharge contact as per usual practice. At 12 months, the primary outcomes were engagement and retention in the adult service and secondary outcomes included hemoglobin A1c (HbA1c), diabetes-related hospitalizations, microvascular complication appearance, and global self-worth. RESULTS: Most CTP participants (11/14) and all SCP (12/12) participants (P = 0.2) transferred to an adult diabetes service; the median time to transfer was 14-15 wk. Overall, participants' frequency of adult diabetes service visits was sub-optimal but their retention in adult care was high. The only group difference was a higher HbA1c at baseline and follow-up in the CTP group. However, a general linear model found that follow-up HbA1c increased by 1.2% for each percentage increase in baseline HbA1c [95% confidence interval (0.4, 1.9; P = 0.01)], independent of treatment group. CONCLUSIONS: Despite the challenges in recruiting adequate numbers, these findings provide valuable insights for future T1DM transition RCTs that are needed to build a more solid evidence-base in this field.

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.

Population-based incidence of diabetes in Australian youth aged 10-18 yr: increase in type 1 diabetes but not type 2 diabetes.

BACKGROUND: Global incidence of childhood type 2 diabetes has increased, with a greater rise amongst certain ethnic groups. OBJECTIVES: To examine the change in the incidence of type 1 and type 2 diabetes in Australian youth, aged 10-18 yr, in New South Wales, Australia. METHODS: Prospective population-based incidence study (2001-2008). Primary case ascertainment was from the Australasian Paediatric Endocrine Group Diabetes Register, secondary independent ascertainment from the National Diabetes Register. RESULTS: There were 202 incident cases of type 2 diabetes (96 boys, 48%). The mean age at diagnosis (±SD) was 14.6 ± 2.5 yr; 93% were overweight (International Obesity Taskforce Grade ≥1). Mean HbA1c was 8.8 ± 2.8%. Ethnicity was Caucasian 31%, Indigenous Australian 20%, Southeast Asian 11%, North African/Middle Eastern 9%, and NewZealander/Melanesian/Polynesian 8%. The mean annual incidence of type 2 diabetes was 3.0 per 100 000 per year (95% confidence interval (CI): 2.6-3.4) and did not change over time. The mean annual incidence of type 1 diabetes was 22.0 per 100 000 per year (95% CI: 20.8-23.1), and increased by 3.8% per year [incidence rate ratio IRR: 1.04, 95% CI: 1.02-1.06, p = 0.001]. Incidence was higher in Indigenous vs. non-Indigenous youth, IRR: 6.9 (95% CI: 4.7-10.2, p < 0.001). CONCLUSION: In 10-18 yr old youth, in Australia, the incidence of type 2 diabetes has remained steady during the last decade; however, the incidence of type 1 diabetes continues to rise. Most common diabetes in Australian youth is type 1 diabetes.

Optimal macronutrient content of the diet for adolescents with prediabetes; RESIST a randomised control trial.

CONTEXT: Prediabetes and clinical insulin resistance in adolescents are rapidly emerging clinical problems with serious health outcomes. OBJECTIVE: The objective of this study was to determine the efficacy of 2 structured lifestyle interventions, both differing in diet macronutrient composition, on insulin sensitivity. DESIGN: This study was a randomized controlled trial, known as Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers, in 2 hospitals in Sydney, Australia. PARTICIPANTS: Participants included overweight or obese 10- to 17-year-olds with either prediabetes and/or clinical features of insulin resistance. INTERVENTION: At baseline adolescents were prescribed metformin and randomized to a structured diet, which was either high carbohydrate or moderate carbohydrate with increased protein. The program commenced with a 3-month dietary intervention, with the addition of an exercise intervention in the next 3 months. OUTCOMES: The outcomes included an insulin sensitivity, anthropometry, and cardiometabolic profile at 6 months. RESULTS: One hundred eleven subjects (66 girls) were recruited and 98 subjects (58 girls) completed the 6-month intervention. After 3 months the mean insulin sensitivity index increased by 0.3 [95% confidence interval (CI) 0.2-0.4]. After 6 months the mean insulin (picomoles per liter) to glucose ratio (millimoles per liter) decreased by 7.2 [95%CI -12.0 to -2.3], body mass index, expressed as a percentage of the 95th centile, decreased by 9% (95% CI -3 to -15), but there was no significant change in the lipids. There were no significant differences in outcomes between the diet groups at any time point. CONCLUSIONS: These results are in contrast with our hypothesis that adolescents randomized to the increased protein diet would have better outcomes. Further strategies are required to better address prediabetes and clinical features of insulin resistance in adolescents.

Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism.

BACKGROUND/AIMS: Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. METHODS: A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. RESULTS: After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) vs. only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120-156 on the old regimen. She was discharged home. CONCLUSION: This practical regimen improved sodium control, parental independence, and allowed discharge home.

Once daily insulin detemir in cystic fibrosis with insulin deficiency.

The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fibrosis (CF). 12 patients with early insulin deficiency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV(1)) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (-0.45±0.38, -7.9±12.8%, -5.8±14.3%) and in the subgroup with early insulin deficiency (-0.41±0.43, -9.8±9.3%, -6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV(1) and Δ%FVC significantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin deficiency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.

Increased detection of cystic-fibrosis-related diabetes in Australia.

OBJECTIVES: To estimate the incidence of cystic-fibrosis-related diabetes (CFRD) in youth from New South Wales (NSW) and the Australian Capital Territory (ACT), Australia and to examine demographic/clinical features at diagnosis. METHODS: Incident cases of CFRD in young people aged ≤ 18 years diagnosed during 2000 to 2008 were identified from four paediatric cystic fibrosis (CF) clinics and the NSW/ACT Australasian Paediatric Endocrine Group Diabetes Register. RESULTS: CFRD was diagnosed in 41 cases (59% girls). The estimated mean annual incidence of CFRD among patients with CF was 9.4 per 1000 person years (95% CI 6.8 to 12.8). Incidence increased from 2.0 per 1000 person years in 2000 to 22.1 per 1000 in 2008 (incidence RR 1.3, 95% CI 1.1 to 1.4). Haemoglobin A1c (HbA1c) was abnormal in the majority at diagnosis: median HbA1c was 6.9% (6.2-8.1%). More cases were diagnosed using an oral glucose tolerance test in 2007-2008 compared with previous years (61% vs 6%, p<0.001). CONCLUSIONS: CFRD is increasingly recognised and now affects approximately one in five young people with CF. The rising incidence is likely to be due to increased detection, resulting from greater awareness and changes in screening practices. Widespread uptake of consensus guidelines for screening will ensure accurate case detection, but will also impact on patient care and resource allocation.

Persistently autoantibody negative (PAN) type 1 diabetes mellitus in children.

BACKGROUND: Autoantibody-negative children diagnosed with type 1 diabetes might have unrecognized monogenic or type 2 diabetes. RESEARCH DESIGN AND METHODS: At diagnosis of type 1 diabetes (between ages 0.5 and 16.3 yr, n = 470), autoantibodies [glutamic acid decarboxylase (GAD), insulinoma-associated protein 2 (IA2), insulin autoantibodies (IAA), and/or islet cell antibody (ICA)] were positive (ab+) in 330 and negative in 37 (unknown in 103). Autoantibody-negative patients were retested at median diabetes duration of 3.2 yr (range 0.9-16.2) for autoantibodies (GAD, IA2, ZnT8), human leukocyte antigen (HLA) typing, non-fasting C-peptide, and sequencing of HNF4A, HNF1A, KCNJ11, and INS. RESULTS: Nineteen (5% of 367) remained persistently autoantibody negative (PAN), 17 were positive on repeat testing (PORT), and 1 refused retesting. No mutations were found in PORT. One PAN was heterozygous for P112L mutation in HNF1A and transferred from insulin to oral gliclazide. Another PAN transferred to metformin and the diagnosis was revised to type 2 diabetes. The remaining 17 PAN were indistinguishable from the ab+ group by clinical characteristics. HLA genotype was at high risk for type 1 diabetes in 82% of remaining PAN and 100% of PORT. After excluding patients with diabetes duration <1 yr, C-peptide was detectable more frequently in the remaining PAN (7/16) and PORT (6/17) than in a random selection of ab+ (3/28, p = 0.03). CONCLUSIONS: The diagnosis of type 1 diabetes should be reevaluated in PAN patients, because a subset has monogenic or type 2 diabetes. The remaining PAN have relatively preserved C-peptide compared with ab+, suggesting slower ß-cell destruction, but a very high frequency of diabetogenic HLA, implying that type 1B (idiopathic) diabetes is rare.

Vitamin D deficiency in children with inflammatory bowel disease.

BACKGROUND: Osteopenia and osteoporosis are commonly seen in inflammatory bowel disease (IBD). Vitamin D deficiency potentially contributes to diminished bone acquisition in childhood. OBJECTIVES: The objectives of this study were to assess vitamin D in a group of Australian children with IBD and to ascertain associations between vitamin D status and key clinical factors, for example disease location and severity. METHODS: Data were obtained retrospectively from the records of children with IBD who had at least one measurement of serum 25-hydroxyvitamin D (25(OH)D) over a two-year period. Demographic variables, disease activity, inflammatory markers, disease location, duration, and therapy were recorded. Moderate and severe deficiency were defined as 25(OH)D <51 nmol/l and <30 nmol/l, respectively. Insufficiency was defined as 25(OH)D between 51 and 75 nmol/l. RESULTS: Overall, the mean 25(OH)D level in 78 children (104 measurements) was 71.2 (SD ± 26.5) nmol/l. Fifteen (19%) children were vitamin D deficient and 30 (38%) children were insufficient. Levels of 25(OH)D were not associated with disease location or use of immunosuppressive drugs. Children with vitamin D deficiency had greater corticosteroid exposure than those with normal status (P = 0.001). The mean 25(OH)D of 38 children treated with nutritional therapy at diagnosis was higher than for 17 children initially treated with corticosteroids (P = 0.04). CONCLUSIONS: A high proportion of these Australian children with IBD were vitamin D deficient. This emphasizes the importance of monitoring vitamin D status, and treating deficiency, in the management of pediatric IBD. The possible benefit of nutritional therapy in protection against vitamin D deficiency requires further prospective study.

Bone mineral content and density in Rett syndrome and their contributing factors.

This study used densitometry to investigate the areal bone mineral density (aBMD) and bone mineral content (BMC) in an Australian Rett syndrome cohort and to assess how factors such as genotype, epilepsy, BMI, and mobility affect these parameters. The influence of lean tissue mass (LTM) and bone area (BA) on total body BMC (TBBMC) was also investigated. Participants, recruited from the Australian Rett Syndrome Database (ARSD), had TBBMC and lumbar spine (LS) and femoral neck (FN) aBMD measured using Dual energy x-ray absorptiometry. Mean height standardized Z scores and CIs for the bone outcomes were obtained from multiple regression models. The mean height Z score for the FN aBMD was low at -2.20, while the LS aBMD was -0.72. The TBBMC mean height Z score was -0.62, although once adjusted for BA and LTM, the mean was above zero, suggesting that low BMC can be explained by narrow bones and decreased muscle mass, likely secondary to decreased mobility. Multiple linear regression identified the p.R168× and p.T158M mutations as the strongest predictors of low aBMC and BMD for all bone outcomes. The strong relationship between genotype, BMC, and aBMD is likely underpinned by the strong relationship between LTM, mobility, and bone outcome measures.

Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

BACKGROUND: Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT) is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. METHODS/DESIGN: This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm) 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet.The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. DISCUSSION: Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With appropriate management these conditions are potentially reversible or at least their progression can be delayed. This research study is the first trial designed to provide much needed data on the effective dietary management for this cohort. This study will inform clinical practice guidelines for adolescents with clinical insulin resistance and may assist in preventing metabolic complications, type 2 diabetes and early cardiovascular disease. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number ACTRN12608000416392.

Effect of exclusive enteral nutrition on bone turnover in children with Crohn's disease.

BACKGROUND: Poor bone acquisition and increased fracture risk are significant complications associated with Crohn's disease (CD). The aim of this study was to determine the effects of 8 weeks of exclusive enteral nutrition (EEN) therapy upon markers of bone turnover in children with newly diagnosed CD. METHODS: Twenty-three children with newly diagnosed CD and 20 controls (without CD) were enrolled. Children with CD were treated with 8 weeks of EEN. Inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelets], nutritional markers (height, weight), and bone markers [C-terminal telopeptides of Type-1 collagen (CTX) and bone specific alkaline phosphatase (BAP)] were measured prior to and following therapy. RESULTS: At diagnosis, children with CD had elevated serum CTX (2.967 +/- 0.881 ng/ml) compared to controls (2.059 +/- 0.568 ng/ml; P = 0.0003). Following the period of EEN, CTX levels fell significantly (2.260 +/- 0.547 ng/ml; P = 0.002), while serum BAP levels (51.24 +/- 31.31 microg/L at diagnosis; control serum BAP = 66.80 +/- 23.23 microg/L; P = 0.07) increased significantly (64.82 +/- 30.51 microg/L; P = 0.02), with both normalizing to control levels. CONCLUSIONS: As well as reducing inflammation, decreasing disease activity, and improving nutrition in children with newly diagnosed CD, EEN therapy also normalized serum markers of bone turnover, suggesting an improvement in bone health. Further investigations of short- and long-term effects of EEN on bone density and overall bone health are now required.

Insulin allergy desensitization with simultaneous intravenous insulin and continuous subcutaneous insulin infusion.

Persistent 'IgE-mediated' insulin allergy (type 1 allergy) (1), unresponsive to changes in insulin type or the use of antihistamines, necessitates desensitization. A number of case reports (2-7) and recent reviews (8, 9) have demonstrated that desensitization can be achieved with continuous subcutaneous insulin infusion (CSII), but in type 1 diabetes mellitus, the need to slowly increase insulin dose from sub-therapeutic levels competes with the need for glycaemic control and suppression of ketogenesis. Tolerance to intravenous (IV) insulin despite persistent life-threatening allergic reactions to subcutaneous human insulin (bolus or CSII) has been recently described (10). We present the cases of two unrelated 9-yr-old boys with persistent generalized urticarial reactions to subcutaneous injections of all available insulin types, despite treatment with oral antihistamines. After failed rapid desensitization to insulin delivered by either subcutaneous injection or CSII, the concurrent use of IV insulin allowed desensitization to CSII over 5-6 d.

Diagnosis and management of childhood obesity: a survey of general practitioners in South West Sydney.

AIM: To describe general practitioners' (GPs) diagnosis and management of overweight and obesity in children, their attitudes regarding obesity and their awareness of National Health and Medical Research Council (NHMRC) clinical practice guidelines. METHOD: A cross-sectional written survey of members of the Liverpool Division of General Practice (located in South West Sydney, Australia). RESULTS: Of 137 questionnaires sent, 85 (62%) were returned. Although the majority prescribed the correct interventions, there was variability in complications screening, ranging from 75% screening for psychosocial problems to 30% for fatty liver. Less than a third (28%) of GPs used NHMRC guidelines in their practice and only 9% used body mass index charts to correctly diagnose childhood obesity. GPs felt that childhood obesity was a significant issue and identified parental denial and lack of community support as barriers to treatment. CONCLUSION: Although NHMRC guideline adherence was far from universal, the GPs in our survey are motivated and aware of the importance of managing childhood obesity. If the primary care approach is to work, then GPs need support and education in an environment where there is greater community awareness of the impact of childhood obesity.