Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study.

AIMS/HYPOTHESIS: The aim of the study was to investigate whether a very-low-energy diet (VLED) is a feasible and acceptable treatment option for type 2 diabetes in children and adolescents, and whether adherence can lead to rapid weight loss, reversal of type 2 diabetes and reduced liver fat as seen in adult studies. METHODS: Eight participants with type 2 diabetes and obesity, aged 7-16 years, non-medicated (n = 1) or treated with metformin (n = 7) and in some cases insulin (n = 3), followed a VLED (<3360 kJ/day) for 8 weeks, then transitioned to a hypocaloric diet (∼6300 kJ/day) that they followed to 34 weeks. HbA1c, fasting glucose and 2 h post-glucose load plasma glucose (2hG) were determined from fasting blood and an OGTT. Liver fat concentration was quantified using proton magnetic resonance spectroscopy. Adherence was defined as ≥5% weight loss during the 8 week VLED. RESULTS: Adherers (n = 5) and non-adherers (n = 3) had median weight loss of 7.5% and 0.5%, respectively, at 8 weeks. Overall, HbA1c (mean [SE] 8.1% [0.7%] to 6.6% [0.5%]; p = 0.004) and 2hG (15.6 [1.6] mmol/l to 11.3 [1.0] mmol/l; p = 0.009) were significantly reduced at 8 weeks compared with baseline. Liver fat was also significantly reduced from baseline (14.7% [2.2%]) to 8 weeks (5.8% [1.7%]; p = 0.001). Only three out of eight participants met non-alcoholic fatty liver disease (NAFLD) criteria (≥5.5%) at 8 weeks, compared with eight out of eight at baseline. The three participants on insulin therapy at baseline were able to cease therapy during the 8 week VLED. At 34 weeks, adherers (n = 5) achieved 12.3% weight loss, none met NAFLD criteria and four did not meet American Diabetes Association criteria for type 2 diabetes. CONCLUSIONS/INTERPRETATION: A VLED appears to be a feasible treatment option for some youth with type 2 diabetes on metformin therapy. Youth who agree to participate and adhere to a VLED achieve rapid weight loss, dramatic reductions in liver fat and reversal of type 2 diabetes. This highlights the capacity of a VLED to be used as a first-line treatment option in newly diagnosed youth. A larger trial with a control group and longer follow-up will be required to encourage a change in standard treatment. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number (ACTRN) ACTRN12616000375459 ( www.ANZCTR.org.au/ACTRN12616000375459.aspx ).

Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

BACKGROUND AND OBJECTIVE: Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. METHODS: Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. RESULTS: In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. CONCLUSION: We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only.

Can early weight loss, eating behaviors and socioeconomic factors predict successful weight loss at 12- and 24-months in adolescents with obesity and insulin resistance participating in a randomised controlled trial?

BACKGROUND: Lifestyle interventions in adolescents with obesity can result in weight loss following active intervention but individual responses vary widely. This study aimed to identify predictors of weight loss at 12- and 24-months in adolescents with obesity and clinical features of insulin resistance. METHODS: Adolescents (n = 111, 66 girls, aged 10-17 years) were participants in a randomised controlled trial, the RESIST study, examining the effects of two diets differing in macronutrient content on insulin sensitivity. Eighty-five completed the 12-month program and 24-month follow-up data were available for 42 adolescents. Change in weight was determined by BMI expressed as a percentage of the 95th percentile (BMI95). The study physician collected socioeconomic data at baseline. Physical activity and screen time, and psychological dimensions of eating behavior were self-reported using the validated CLASS and EPI-C questionnaires, respectively. Stepwise multiple regressions were conducted to identify models that best predicted change in BMI95 at 12- and 24-months. RESULTS: Mean BMI95 was reduced at 12-months compared with baseline (mean difference [MD] ± SE: -6.9 ± 1.0, P < 0.001) but adolescents had significant re-gain from 12- to 24-months (MD ± SE: 3.7 ± 1.5, P = 0.017). Participants who achieved greater 12-month weight loss had: greater 3-month weight loss, a father with a higher education, lower baseline external eating and parental pressure to eat scores and two parents living at home. Participants who achieved greater 24-month weight loss had: greater 12-month weight loss and a lower baseline emotional eating score. CONCLUSIONS: Early weight loss is consistently identified as a strong predictor of long-term weight loss. This could be because early weight loss identifies those more motivated and engaged individuals. Patients who have baseline factors predictive of long-term weight loss failure may benefit from additional support during the intervention. Additionally, if a patient does not achieve early weight loss, further support or transition to an alternate intervention where they may have increased success may be considered. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071.

Zinc Intake, Zinc Bioavailability and Plasma Zinc in Obese Adolescents with Clinical Insulin Resistance Following Low Energy Diets.

BACKGROUND: Zinc has a critical role in metabolism and growth. This study aims to determine the effects of low-energy diets differing in macronutrient composition on zinc intake, estimated zinc bioavailability (phytate:zinc molar ratio) and plasma zinc concentration and associations between zinc status and cardiometabolic markers in obese adolescents with clinical insulin resistance (IR). METHODS: Eighty-seven obese adolescents (10-17 years, body mass index z-score 2.3 ± 0.37) with clinical IR were randomized to a low-energy diet (6.0-8.0 MJ), which was either high carbohydrate or moderate carbohydrate with increased protein. Twenty-four-hour dietary recalls were collected at 6, 9 and 12 weeks. Plasma zinc concentration and cardiometabolic markers were assessed at baseline and 12 weeks. RESULTS: Zinc intake did not differ between the 2 diet groups (p = 0.612). The high-carbohydrate group had a higher phytate intake (894 vs. 671 mg, p = 0.018) and phytate:zinc molar ratio (9.4 vs. 7.4, p = 0.009) than the increased-protein group. Plasma zinc concentration did not change from baseline in either of the diet groups, but correlated positively with zinc intake (r = 0.235, p = 0.042) and % energy from protein (r = 0.383, p = 0.001), and inversely with % energy from carbohydrate (r = -0.296, p = 0.010). CONCLUSIONS: Low energy diets for obese adolescents at risk of diabetes may need increased protein content to optimize zinc bioavailability.

Bioelectrical impedance analysis to estimate body composition, and change in adiposity, in overweight and obese adolescents: comparison with dual-energy x-ray absorptiometry.

BACKGROUND: There is a need for a practical, inexpensive method to assess body composition in obese adolescents. This study aimed to 1) compare body composition parameters estimated by a stand-on, multi-frequency bioelectrical impendence (BIA) device, using a) the manufacturers' equations, and b) published and derived equations with body composition measured by dual-energy x-ray absorptiometry (DXA) and 2) assess percentage body fat (%BF) change after a weight loss intervention. METHODS: Participants were 66 obese adolescents, mean age (SD) 12.9 (2.0) years. Body composition was measured by Tanita BIA MC-180MA (Tanita BIA8) and DXA (GE-Lunar Prodigy). BIA resistance and reactance data at frequencies of 5, 50, 250 and 500 kHz, were used in published equations, and to generate a new prediction equation for fat-free mass (FFM) using a split-sample method. Approximately half (n = 34) of the adolescents had their body composition measured by DXA and BIA on two occasions, three to nine months apart. RESULTS: The correlations between FFM (kg), fat mass (kg) and %BF measured by BIA and DXA were 0.92, 0.93 and 0.78, respectively. The Tanita BIA8 manufacturers equations significantly (P < 0.001) overestimated FFM (4.3 kg [-5.3 to 13.9]) and underestimated %BF (-5.0% [-15 to 5.0]) compared to DXA. The mean differences between BIA derived equations and DXA measured body composition parameters were small (0.4 to 2.1%), not significant, but had large limits of agreements (~ ±15% for FFM). After the intervention mean %BF loss was similar by both methods (~1.5%), but with wide limits of agreement. CONCLUSION: The Tanita BIA8 could be a valuable clinical tool to measure body composition at the group level, but is inaccurate for the individual obese adolescent.

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.

Comparison of Centers for Disease Control and Prevention and World Health Organization references/standards for height in contemporary Australian children: analyses of the Raine Study and Australian National Children's Nutrition and Physical Activity cohorts.

AIM: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children; (ii) To examine the implications for identifying short stature and eligibility for GH treatment. METHODS: Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. RESULTS: Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. CONCLUSIONS: Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.

Effect of a prescriptive dietary intervention on psychological dimensions of eating behavior in obese adolescents.

BACKGROUND: Overweight adolescents are more likely to have dysfunctional eating behaviours compared to normal weight adolescents. Little is known about the effects of obesity treatment on the psychological dimensions of eating behavior in this population. OBJECTIVE: To examine the effects of a prescriptive dietary intervention on external eating (eating in response to food cues, regardless of hunger and satiety), emotional eating and dietary restraint and their relation to weight loss. Parental acceptability was also examined. METHOD: This is a secondary study of a 12-month randomized trial, the RESIST study, which examined the effects of two diets on insulin sensitivity. Participants were 109 obese 10- to 17-year-olds with clinical features of insulin resistance. The program commenced with a 3-month dietary intervention using a structured meal plan, with the addition of an exercise intervention in the next 3 months and followed by a 6 month maintenance period.This paper presents changes in eating behaviors measured by the Eating Pattern Inventory for Children and parent rated diet acceptability during the first 6 months of the trial. As there was no difference between the diets on outcome of interest, both diet groups were combined for analyses. RESULTS: After 6 months, the proportion of participants who reported consuming more in response to external eating cues decreased from 17% to 5% (P = 0.003), whereas non- emotional eating increased from 48% to 65% (p = 0.014). Dietary restraint and parental pressure to eat remained unchanged. A reduction in external eating (rho = 0.36, P < 0.001) and a reduction in dietary restraint (r = 0.26, P = 0.013) were associated with greater weight loss at 3 and 6 months, respectively. Overall this approach was well accepted by parents with 72% of parents considered that their child would be able to follow the meal plan for the longer term. CONCLUSIONS: In the short to medium term, a prescriptive dietary intervention approach is a well-accepted and suitable option for obese adolescents with clinical features of insulin resistance. It may reduce external and emotional eating, led to modest weight loss and did not cause any adverse effect on dietary restraint. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071.

Growth and pubertal development of adolescent boys on stimulant medication for attention deficit hyperactivity disorder.

OBJECTIVE: To investigate the growth and pubertal attainment of boys with attention deficit hyperactivity disorder (ADHD) on stimulant medication. DESIGN, SETTING AND PARTICIPANTS: Longitudinal study of boys aged 12.00-15.99 years at recruitment in 2005-2011, with stimulant-treated ADHD for at least 3 years, attending three paediatric practices (subjects), compared with longitudinal data from 174 boys from the Nepean longitudinal study (controls). MAIN OUTCOME MEASURES: Subjects' growth parameters before treatment were compared with controls aged 7 or 8 years; growth parameters and longitudinal changes on treatment to ages 12.00-13.99 and 14.00-15.99 years were compared with controls reviewed at 13 and 15 years of age, respectively. The subjects' pubertal staging and height velocity were related to their treatment history. RESULTS: Sixty-five subjects were recruited; mean duration of treatment was 6.3 ± 1.9 years. At baseline, their growth parameters were not significantly different from those of the controls after adjusting for age. Compared with the controls, after adjusting for current age and baseline growth parameter z score, subjects aged 12.00-13.99 years had significantly lower weight and body mass index (P < 0.01), and those aged 14.00-15.99 years had significantly lower height and weight (P < 0.05). At 12.00-13.99 years of age, the subjects were comparable to the controls in their pubertal development adjusted for age, but those aged 14.00-15.99 years reported significant delay (mean Tanner stage, 3.6 for subjects v 4.0 for controls; P < 0.05). The dose of medication was inversely correlated with the height velocity from baseline to 14.00-15.99 years of age (P < 0.05). CONCLUSIONS: Prolonged treatment (more than 3 years) with stimulant medication was associated with a slower rate of physical development during puberty. To maintain adequate height velocity during puberty, we recommend keeping the dose as low as possible.

Growth hormone regimens in Australia: analysis of the first 3 years of treatment for idiopathic growth hormone deficiency and idiopathic short stature.

OBJECTIVE: To investigate response to growth hormone (GH) in the first, second and third years of treatment for all idiopathic GH-deficient (GHD) and idiopathic short stature (ISS) patients in Australia. CONTEXT: Eligibility for subsidized GH treatment in Australia is determined on auxological criteria for the indication of Short Stature and Slow Growth (SSSG), which includes ISS (SSSG-ISS). The biochemical GHD (BGHD, peak GH < 10 mU/l) and SSSG indications are treated similarly: starting dose of 4·5 mg/m(2)/week with provision for incremental dosing. Some ISS patients were specifically diagnosed with familial short stature (SSSG-FSS). DESIGN: Responses for each year of treatment for BGHD, SSSG-ISS and SSSG-FSS cohorts were compared in relation to influencing variables and with international benchmarks. The effect of incremental dosing was assessed. PATIENTS: Australian BGHD, SSSG-ISS and SSSG-FSS patients who had completed 1, 2, or 3 years of treatment and were currently receiving GH. MEASUREMENTS: Growth hormone dose, change in height-standard deviation score (ΔSDS) and growth velocity (GV). RESULTS: First-year response was 2-3 times greater than that in subsequent years: ΔSDS(1st year) = 0·92, 0·50 and 0·46 for BGHD, SSSG-ISS and SSSG-FSS, respectively. Responses were similar to international reports and inversely related to age at commencement of GH. First-year GV-for-age for BGHD patients was similar to international standards for idiopathic GHD. However, girls had an inferior response to boys when treatment commenced at <6 years of age. First-year GV-for-age for SSSG-ISS/FSS patients was less than ISS standards. Dose increments attenuated the first- to second-year decline in response to BGHD but marginally improved the responses for SSSG-ISS/FSS. CONCLUSIONS: The Australian auxology-based GH programme produces comparable responses to international programmes. A lower starting dose is offset by the initiation of treatment at younger ages. Incremental dosing does not appear optimal. A first-year dose of 6·4-6·9 mg/m(2)/week for GHD and 8·9 mg/m(2)/week for ISS with early commencement of GH treatment may be most efficacious.

Growth hormone treatment for Turner syndrome in Australia reveals that younger age and increased dose interact to improve response.

OBJECTIVE: To investigate response to growth hormone (GH) in the first, second and third years of treatment in the total clinical cohort of Turner syndrome (TS) patients in Australia. CONTEXT: Short stature is the most common clinical manifestation of TS. GH treatment improves growth. DESIGN: Response was measured for each year of treatment. Stepwise multiple regression analyses were used to identify factors that significantly influenced response. PATIENTS: Prepubertal TS patients who completed 1 year (n=176), 2 years (n=148), or 3 years (n=117) of treatment and were currently receiving GH. MEASUREMENTS: Change in TS specific Height Standard Deviation Score (ΔTSZ) was the main response variable used. Major influencing variables considered included dose, starting age and height, BMI, bone age delay, karyotype, parental height, and interactions between dose and starting age or height. RESULTS: Response was greatest in first year and declined thereafter (median ΔTSZ: 1st year= +0·705, 2nd year= +0·439, 3rd year= +0·377) despite the median dose increasing [1st year= 5·5 mg/m(2) /week (0·23 mg/kg/week), 2nd year= 6·4(0·24), 3rd year= 7·2(0·26)]. An Age*Dose interaction was identified influencing first, second year, and total ΔTSZ. The ΔTSZ over 3 years was significantly influenced by first-year dose. Dose increments only attenuated the general decline in response. An acceptable first-year response (ΔTSZ>1·01) was achieved by only 17·6% of patients. CONCLUSIONS: Growth response is greatest and most influenced by dose in the first year. Dose in first year is a major factor contributing to total response. A starting Age*Dose interaction effect was observed such that young girls on a high dose respond disproportionately better. Optimal GH treatment of short stature in TS thus requires early initiation with the highest safe dose in the first year.

Waist circumference and waist-to-height ratio in Han Chinese children living in Chongqing, south-west China.

OBJECTIVE: To derive age- and sex-specific reference values for waist circumference (WC) and waist-to-height ratio (WHtR) for Han Chinese children and adolescents and to establish the prevalence of excess central adiposity in our study population. DESIGN: Cross-sectional study of schoolchildren attending randomly selected primary and secondary schools in south-west China in October 2003 and April 2004. Anthropometry was measured using standard procedures. The LMS method was used to construct smoothed WC and WHtR percentile curves. Overweight and obesity were defined by the International Obesity Task Force (IOTF) criteria and the Working Group on Obesity in Children. Excess central adiposity fat was defined by previously published WC cut-points and a WHtR ≥ 0.5. SETTING: Primary and secondary schools in Chongqing, south-west China. SUBJECTS: A total of 7326 (49.2 % boys) Han Chinese students at 5-17 years old. RESULTS: On the basis of the IOTF criteria, 26.4 % of boys were overweight or obese compared with 16.4 % of girls (P < 0.001). WC cut-points identified 31 % of boys and 28 % of girls as having excess central adiposity, whereas using the WHtR criterion, 14.8 % of boys and 5.6 % of girls were identified. Young boys (5-12 years) had a significantly (P < 0.001) higher WHtR than girls. CONCLUSIONS: We have constructed WC and WHtR percentile curves for Han Chinese children and adolescents living in Chongqing. Our measurements were based on a student population with a relatively high rate of overweight and obesity. These data will provide a point of reference for future studies measuring the prevalence of overweight and obesity in China.

Evaluation of glycaemic status in young people with clinical insulin resistance; fasting glucose, fasting insulin or an oral glucose tolerance test?

OBJECTIVE: It is important to identify young people with prediabetes for early intervention. However, it is unclear how to best screen overweight and obese young people for prediabetes. The objective of this study was to compare fasting indices with an oral glucose tolerance test (OGTT) in diagnosing prediabetes. DESIGN: Retrospective review. PATIENTS: A total of 224 young people, aged 12.0 years (range: 3.2-17.3 years), with clinical features of insulin resistance, who had an OGTT between 2000 and 2007 at a tertiary children's hospital, Sydney, Australia. MEASUREMENTS: Oral glucose tolerance test. RESULTS: A total of 168 (75%) participants had normal glucose tolerance, 45 (20%) had prediabetes and 11 (5%) had type 2 diabetes; 29 of those with prediabetes and 10 with type 2 diabetes were identified by fasting glucose criteria alone. Young people with normal fasting glucose and fasting insulin < or =180 pmol/l had lower insulin resistance (homeostasis model assessment median 1.9 vs. 4.2, P < 0.001), higher insulin sensitivity index (2.4 vs. 1.0, P < 0.001) and a lower early insulin response (insulinogenic index 2.5 vs. 4.1, P < 0.001) compared to those with normal fasting glucose and higher fasting insulin levels. If a fasting insulin cut point (< or =180 pmol/l) was used in addition to fasting glucose to determine the need for an OGTT, 114 (68%) young people with normal glucose tolerance would have avoided the test. By contrast, the diagnosis of impaired glucose tolerance, identified by an OGTT, would have been missed in three children. CONCLUSION: Fasting glucose and insulin levels should be measured in young people with insulin resistance before undertaking a time- and resource-intensive OGTT.

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.

Assessing guideline adherence in the management of type 1 diabetes mellitus in Australian children: a population-based sample survey.

INTRODUCTION: To estimate adherence to clinical practice guidelines in selected settings at a population level for Australian children with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: Medical records of children with type 1 diabetes mellitus aged 0-15 years in 2012-2013 were targeted for sampling across inpatient, emergency department and community visits with specialist pediatricians in regional and metropolitan areas and tertiary pediatric hospitals in three states where approximately 60% of Australian children reside. Clinical recommendations extracted from two clinical practice guidelines were used to audit adherence. Results were aggregated across types of care (diagnosis, routine care, emergency care). RESULTS: Surveyors conducted 6346 indicator assessments from an audit of 539 healthcare visits by 251 children. Average adherence across all indicators was estimated at 79.9% (95% CI 69.5 to 88.0). Children with type 1 diabetes mellitus have higher rates of behavioral and psychological disorders, but only a third of children (37.9%; 95% CI 11.7 to 70.7) with suboptimal glycemic control (eg, hemoglobin A1c >10% or 86 mmol/mol) were screened for psychological disorders using a validated tool; this was the only indicator with <50% estimated adherence. Adherence by care type was: 86.1% for diagnosis (95% CI 76.7 to 92.7); 78.8% for routine care (95% CI 65.4 to 88.9) and 83.9% for emergency care (95% CI 78.4 to 88.5). CONCLUSIONS: Most indicators for care of children with type 1 diabetes mellitus were adhered to. However, there remains room to improve adherence to guidelines for optimization of practice consistency and minimization of future disease burden.

Paediatric bilateral adrenal phaeochromocytomas in association with a novel mutation in the von Hippel Lindau gene.

Functional phaeochromocytoma and paraganglioma are rare in children and adolescents. We report a 12-year-old male with bilateral phaeochromocytoma in whom germ line testing identified a novel mutation in the von Hippel Lindau gene. Early age of onset, bilateral phaeochromocytoma and other clinical features should prompt germ line DNA testing for mutations in genes associated with familial phaeochromocytoma and paraganglioma syndromes.

Vitamin D levels in childhood and adolescence and cardiovascular risk factors in a cohort of healthy Australian children.

As the prevalence of obesity appears to be increasing in Australia's youth the overall objective of this study was to examine serum 25-hydroxyvitamin D (25OHD) concentrations in a cohort of 8-year-olds (n=249) followed up at age 15 (n=162) and explore associations between 25OHD with cardiovascular disease (CVD) risk factors in these populations. This was done in two stages: the first, two cross-sectional analyses (at ages 8 and 15); and the second, a prospective analysis from age 8 to 15. At both ages data on 25OHD, blood lipids, and anthropometry were measured. Date of blood draw was used as a surrogate of sunlight exposure. Results were then analysed by multivariate linear analyses taking into account interaction and confounding. Mean 25OHD concentrations decreased from 94±25nmol/L to 63±16nmol/L between age 8 and 15 years (p<0.001). On cross-sectional analysis of 8year olds, no CVD risk factor was found to be significantly associated with 25OHD concentrations. On cross-sectional analysis of 15year olds lower 25OHD levels were significantly associated with higher body fat (adjusted ß=-0.24, p=0.003). Prospectively, lower 25OHD levels in 8-year-old boys, but not girls, were significantly associated with higher blood total cholesterol (adjusted ß=-0.28, p=0.040) and triglyceride levels (adjusted ß=-0.33, p=0.030) at age 15. The limitation of these data is the relatively small sample sizes, however these results suggest that low 25OHD in childhood needs to be further investigated in larger cohort studies as there may be later cardiovascular consequences in adolescence.

Relation of child, caregiver, and environmental characteristics to childhood injury in an urban Aboriginal cohort in New South Wales, Australia.

OBJECTIVE: Despite being disproportionately affected by injury, little is known about factors associated with injury in Aboriginal children. We investigated factors associated with injury among urban Aboriginal children attending four Aboriginal Community Controlled Health Services in New South Wales, Australia. METHODS: We examined characteristics of caregiver-reported child injury, and calculated prevalence ratios of 'ever-injury' by child, family, and environmental factors. RESULTS: Among children in the cohort, 29% (n=373/1,303) had ever broken a bone, been knocked out, required stitches or been hospitalised for a burn or poisoning; 40-78% of first injuries occurred at home and 60-91% were treated in hospital. Reported ever-injury was significantly lower (prevalence ratio ≤0.80) among children who were female, younger, whose caregiver had low psychological distress and had not been imprisoned, whose family experienced few major life events, and who hadn't experienced alcohol misuse in the household or theft in the community, compared to other cohort members. CONCLUSIONS: In this urban Aboriginal child cohort, injury was common and associated with measures of family and community vulnerability. Implications for public health: Prevention efforts targeting upstream injury determinants and Aboriginal children living in vulnerable families may reduce child injury. Existing broad-based intervention programs for vulnerable families may present opportunities to deliver targeted injury prevention.

Body mass index and waist circumference in midchildhood and adverse cardiovascular disease risk clustering in adolescence.

BACKGROUND: Body mass index (BMI) may not indicate the level of central adiposity associated with the clustering of cardiovascular disease (CVD) risk factors. Hence, it has been recommended that waist circumference be used as an alternative measure. OBJECTIVE: The objective was to investigate whether waist circumference in midchildhood is more effective at predicting cardiovascular disease risk clustering in adolescence than is BMI. DESIGN: Anthropometric measurements were made in 342 children aged 8 y. Seven years later, anthropometric measurements were made in 290 participants, and metabolic profiles were determined in 172 participants. RESULTS: At 15 y, between 9.4% and 11.0% of adolescents were defined as having CVD risk clustering. Children who were overweight or obese at 8 y of age were 7 times (odds ratio: 6.9; 95% CI: 2.5, 19.0; P < 0.001) as likely to have CVD risk clustering in adolescence than were their peers who were not overweight or obese. Those with an increased waist circumference at 8 y were 4 times (3.6; 1.0, 12.9; P = 0.061) as likely to have CVD risk clustering in adolescence than were children with a smaller waist circumference. Neither BMI nor waist circumference were predictive of CVD risk clustering if adiposity was not included as a risk factor. CONCLUSIONS: The association between measures of adiposity in midchildhood and later adverse CVD risk is a result of the tracking of adiposity status. Our results do not support the need to measure waist circumference in children, in addition to BMI, to identify those at increased risk of CVD risk factor clustering in adolescence.