Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes.

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)(2) D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35 d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n = 56) than in controls (n = 46) [mean (95%CI) = 78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p = 0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)(2) D [median (IQR) = 89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p = 0.03], or children with established diabetes [137 (113-153) pmol/L, p = 0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown.

The Eat Smart Study: a randomised controlled trial of a reduced carbohydrate versus a low fat diet for weight loss in obese adolescents.

BACKGROUND: Despite the recognition of obesity in young people as a key health issue, there is limited evidence to inform health professionals regarding the most appropriate treatment options. The Eat Smart study aims to contribute to the knowledge base of effective dietary strategies for the clinical management of the obese adolescent and examine the cardiometablic effects of a reduced carbohydrate diet versus a low fat diet. METHODS AND DESIGN: Eat Smart is a randomised controlled trial and aims to recruit 100 adolescents over a 2 1/2 year period. Families will be invited to participate following referral by their health professional who has recommended weight management. Participants will be overweight as defined by a body mass index (BMI) greater than the 90th percentile, using CDC 2000 growth charts. An accredited 6-week psychological life skills program 'FRIENDS for Life', which is designed to provide behaviour change and coping skills will be undertaken prior to volunteers being randomised to group. The intervention arms include a structured reduced carbohydrate or a structured low fat dietary program based on an individualised energy prescription. The intervention will involve a series of dietetic appointments over 24 weeks. The control group will commence the dietary program of their choice after a 12 week period. Outcome measures will be assessed at baseline, week 12 and week 24. The primary outcome measure will be change in BMI z-score. A range of secondary outcome measures including body composition, lipid fractions, inflammatory markers, social and psychological measures will be measured. DISCUSSION: The chronic and difficult nature of treating the obese adolescent is increasingly recognised by clinicians and has highlighted the need for research aimed at providing effective intervention strategies, particularly for use in the tertiary setting. A structured reduced carbohydrate approach may provide a dietary pattern that some families will find more sustainable and effective than the conventional low fat dietary approach currently advocated. This study aims to investigate the acceptability and effectiveness of a structured reduced dietary carbohydrate intervention and will compare the outcomes of this approach with a structured low fat eating plan. TRIAL REGISTRATION: The protocol for this study is registered with the International Clinical Trials Registry (ISRCTN49438757).

Klebsiella pneumoniae bacteraemia complicating rotavirus gastroenteritis in two infants with glucocorticoid deficiency.

Rotavirus gastroenteritis was complicated by Klebsiella Pneumoniae bacteraemia in two infants with glucocorticoid deficient conditions who were treated with 'stress dose' hydrocortisone during their illness. Delayed healing in the context of glucocorticoid administration combined with damage from rotavirus infection may result in increased risk of mucosal invasion by gastrointestinal bacteria and subsequent enteric gram-negative bacteraemia.

The feasibility of a home-based moderate-intensity physical activity intervention in obese children and adolescents.

OBJECTIVES: To explore the feasibility of conducting a 10-week home-based physical activity (PA) programme and evaluate the changes in insulin sensitivity (S(I)) commensurate with the programme in obese young people. DESIGN: Open-labelled intervention. SETTING: Home-based intervention with clinical assessments at a tertiary paediatric hospital. SUBJECTS: 18 obese (body mass index (BMI)>International Obesity Task Force age and sex-specific cut-offs) children and adolescents (8-18 years, 11 girls/7 boys) were recruited. 15 participants (nine girls/six boys, mean+/-SE age 11.8+/-0.6 years, BMI-SD scores (BMI-SDS) 3.5+/-0.1, six prepubertal/nine pubertal) completed the intervention. INTERVENTION: The programme comprised biweekly home visits over 10 weeks with personalised plans implemented aiming to increase moderate-intensity PA. Pedometers and PA diaries were used as self-monitoring tools. The goals were to (1) teach participants behavioural skills related to adopting and maintaining an active lifestyle and (2) increase daily participation in PA. OUTCOME MEASURES: Mean steps/day were assessed. S(I) assessed by the frequently sampled intravenous glucose tolerance test and other components of the insulin resistance syndrome were measured. RESULTS: Mean steps/day increased significantly from 10 363+/-927 (baseline) to 13 013+/-1131 (week 10) (p<0.05). S(I) was also significantly increased, despite no change in BMI-SDS, and remained so after an additional 10-week follow-up. CONCLUSIONS: The results suggest that such a home-based PA programme is feasible. S(I) improved without changes in BMI-SDS. More rigorous evaluations of such programmes are warranted.

A Systematic Review of Pediatric Telediabetes Service Models.

Telediabetes may improve patient access to clinicians who specialize in the management of pediatric diabetes. Due to the diversity of telehealth modes, many different service models for pediatric telediabetes have been developed. This review describes pediatric telediabetes service models identified in the literature, investigates the reported changes in HbA1c of these interventions, and describes enablers and barriers to implementing a telediabetes service. Evaluation of current literature may inform the development and sustainability of telehealth services for pediatric diabetes management. Twenty-nine studies met inclusion criteria and were reviewed. This review has demonstrated that pediatric telediabetes can be delivered by remote monitoring and real-time videoconference modes. Overall, pediatric telediabetes increased interactions between patients and clinicians, improved access to specialized care, and facilitated increased diabetes monitoring. In some contexts, telediabetes also improved short-term glycemic control. Key enablers reported for telediabetes services were integration with existing workflows, dedicated staff, clinician and patient training, appropriate data security, technology with good usability, and the availability of technical support. Barriers included increases in patient responsibilities and clinician workload, and technical issues with equipment and software.

A Randomized Controlled Trial of Two Different Macronutrient Profiles on Weight, Body Composition and Metabolic Parameters in Obese Adolescents Seeking Weight Loss.

OBJECTIVE: Adolescent obesity is difficult to treat and the optimal dietary pattern, particularly in relation to macronutrient composition, remains controversial. This study tested the effect of two structured diets with differing macronutrient composition versus control, on weight, body composition and metabolic parameters in obese adolescents. DESIGN: A randomized controlled trial conducted in a children's hospital. METHODS: Eighty seven obese youth (means: age 13.6 years, BMI z-score 2.2, waist: height ratio 0.65, 69% female) completed a psychological preparedness program and were then randomized to a short term 'structured modified carbohydrate' (SMC, 35% carbohydrate; 30% protein; 35% fat, n = 37) or a 'structured low fat' (SLF, 55% carbohydrate; 20% protein; 25% fat, n = 36) or a wait listed control group (n = 14). Anthropometric, body composition and biochemical parameters were measured at randomization and after 12 weeks, and analyzed under the intention to treat principle using analysis of variance models. RESULTS: After 12 weeks, data was collected from 79 (91%) participants. BMI z-scores were significantly lower in both intervention groups compared to control after adjusting for baseline values, SLF vs. control, mean difference = -0.13 (95%CI = -0.18, -0.07), P<0.001; SMC vs. control, -0.14 (-0.19, -0.09), P<0.001, but there was no difference between the two intervention diet groups: SLF vs. SMC, 0.00 (-0.05, 0.04), P = 0.83. CONCLUSIONS: Both dietary patterns resulted in similar changes in weight, body composition and metabolic improvements compared to control. The use of a structured eating system which allows flexibility but limited choices can assist in weight change and the rigid application of a low fat eating pattern is not exclusive in its efficacy. TRIAL REGISTRATION: International Clinical Trials Registry ISRCTN49438757.

Indexes of insulin resistance and secretion in obese children and adolescents: a validation study.

OBJECTIVE: To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) adolescents using estimates from the modified minimal model frequently sampled intravenous glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS: Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and 11 pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S(i) measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS: There was a significant negative correlation between HOMA-IR and S(i) (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S(i) (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S(i) (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S(i) (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS: HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S(i) assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-beta%, FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.

Vitamin A levels in patients with CF are influenced by the inflammatory response.

BACKGROUND: Serum vitamin A, normally depressed in inflammatory conditions, is frequently low in people with CF. Vitamin A is important in respiratory epithelial regeneration and repair. We hypothesised that serum vitamin A would be associated with inflammation and disease severity. METHODS: Serum vitamin A (as retinol), C-reactive protein (CRP), vitamin E, 25-hydroxy vitamin D (25OHD), 1,25-dihydroxy vitamin D (1,25(OH)(2)D), weight, and lumbar spine bone mineral density (LSBMD) were measured in 138 subjects with CF (5-56 years) and 138 control subjects (5-48 years). FEV(1), presence of CF liver disease (CFLD) and hospital admissions were recorded in those with CF. RESULTS: Serum vitamin A level was lower in CF subjects than in controls (mean, 95% CI: 1.29, 1.0-1.37 vs. 1.80, 1.7-1.87 micromol/l, p < 0.0001), and inversely correlated with CRP (r(s) = -0.37, p < 0.0001). CF subjects with low vitamin A (45%) level had poorer FEV(1), weight z-score, LSBMD z-score, and higher CRP compared with those with normal levels. In the CF group CRP, vitamin E, 1,25(OH)(2)D, presence of CFLD, admissions, and age were associated with vitamin A level. CONCLUSIONS: Serum vitamin A is negatively associated with CRP in subjects with CF, consistent with normal population studies. It is important to distinguish between low serum vitamin A associated with the inflammatory response and that due to poor nutritional stores. The role of vitamin A in CF warrants further study, in the contexts both of chronic recurrent inflammatory disease and acute pulmonary exacerbation.

Predicting success: factors associated with weight change in obese youth undertaking a weight management program.

OBJECTIVE: To explore which baseline physiological and psychosocial variables predict change in body mass index (BMI) z-score in obese youth after 12 weeks of a dietary weight management study. METHODS: Participants were obese young people participating in a dietary intervention trial in Brisbane Australia. The outcome variable was change in BMI z-score. Potential predictors considered included demographic, physiological and psychosocial parameters of the young person, and demographic characteristics of their parents. A multivariable regression model was constructed to examine the effect of potential predictive variables. RESULTS: Participants (n = 88) were predominantly female (69.3%), and had a mean(standard deviation) age of 13.1(1.9) years and BMI z-score of 2.2(0.4) on presentation. Lower BMI z-score (p < 0.001) and insulin resistance (p = 0.04) at baseline, referral from a paediatrician (p = 0.02) and being more socially advantaged (p = 0.046) were significantly associated with weight loss. Macronutrient distribution of diet and physical activity level did not contribute. CONCLUSIONS: Early intervention in obesity treatment in young people improves likelihood of success. Other factors such as degree of insulin resistance, social advantage and referral source also appear to play a role. Assessing presenting characteristics and factors associated with treatment outcome may allow practicing clinicians to individualise a weight management program or determine the 'best-fit' treatment for an obese adolescent.

Neonatal complete generalized glucocorticoid resistance and growth hormone deficiency caused by a novel homozygous mutation in Helix 12 of the ligand binding domain of the glucocorticoid receptor gene (NR3C1).

CONTEXT: Glucocorticoid resistance is a rare genetic condition characterized by reduced sensitivity to cortisol signaling and subsequent hyperactivation of the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The objective was to confirm the diagnosis of glucocorticoid resistance in the patient, to determine the degree of suppression of cortisol and ACTH levels in response to dexamethasone, and to determine the underlying genetic abnormality and functional consequences of the mutation. PATIENT AND METHODS: The patient presented on the first day of life with profound hypoglycemia. Initial cortisol levels were appropriately elevated; however, the patient was found to have persistently elevated levels of both cortisol and ACTH. The baby developed a tanned appearance and severe hypertension and fatigued easily with feeding. Serial oral dexamethasone suppression tests were performed with doses escalating from 0.125 mg to 12 mg dexamethasone given at 2300 h. Sequencing of the glucocorticoid receptor gene was performed along with functional studies of the glucocorticoid receptor. GH secretion was assessed with an arginine glucagon stimulation test. RESULTS: Cortisol and ACTH levels did not suppress with doses of up to 12 mg dexamethasone. A 2-bp deletion was found at amino acid position 773 of the glucocorticoid receptor ligand binding domain. A complete lack of dexamethasone binding and in vitro biological effect was demonstrated. GH stimulation testing was consistent with GH deficiency. CONCLUSION: The homozygous mutation in the ligand-binding domain of the glucocorticoid receptor gene resulted in a functionally inactive glucocorticoid receptor and apparent complete glucocorticoid resistance with biochemical GH deficiency.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement.

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300,000-500,000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

3. Management and prevention of obesity and its complications in children and adolescents.

Obesity in children and adolescents has reached alarming levels--20%-25% of children and adolescents are overweight or obese, and 4.9% of boys and 5.4% of girls are obese. Rates of obesity have increased significantly in Australia from 1985 to 1995, with the prevalence of overweight doubling and obesity trebling. Body mass index (related to reference standards for age and sex) is recommended as a practical measure of overweight and obesity in children, and is used in monitoring individual progress in clinical practice. Obesity in childhood and adolescence may be associated with a range of medical and psychological complications, and can predispose individuals to serious health problems in adult life, including type 2 diabetes, hypertension, dyslipidaemia and non-alcoholic steatohepatitis. Obesity interventions for which there is some evidence include family support, a developmentally appropriate approach, long-term behaviour modification, dietary change, and increased physical activity and decreased sedentary behaviour. Prevention of obesity in children and adolescents requires a range of strategies involving changes in both the microenvironment (eg, housing, neighbourhoods, recreational opportunities) and the macroenvironment (eg, food marketing, transport systems, urban planning).

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls.

Abnormalities of calcium and vitamin D metabolism in cystic fibrosis (CF) are well documented. We tested the hypothesis that alterations in calcium metabolism are related to vitamin D deficiency, and that bone resorption is increased relative to accretion in patients with CF. Calcitropic hormones, electrolytes, osteocalcin (OC) and bone alkaline phosphatase (BAP), (markers of bone mineralisation), urinary deoxypyridinoline [total (t) Dpd, a marker of bone resorption] and lumbar spine bone mineral density (LS BMD), expressed as a z-score, were measured in 149 (81 M) CF and 141 (61 M) control children aged 5.3-10.99 years, adolescents aged 11-17.99 years and adults aged 18-55.9 years. Data were analysed by multiple regression to adjust for age. In patients, FEV(1)% predicted and CRP (as disease severity markers), genotype and pancreatic status (PS) were recorded. The distribution of PTH differed between groups ( P<0.0001), with CF levels both below and above the control range. 25OH vitamin D (25OHD) was not different in control and CF subjects ( P=0.06). Active hormonal vitamin D (1,25(OH)(2)D) was lower in the CF group ( P<0.0001), not explained by 25OHD or disease severity, as was serum magnesium ( P<0.0001). OC was decreased in CF adults ( P=0.004), and tDpd increased in CF adolescents ( P=0.003) and adults ( P=0.03). The ratio of OC to tDpd (a measure of bone coupling) was similar in CF and control children, but decreased in CF adolescents ( P=0.04) and adults ( P=0.02), suggesting decreased overall bone accrual in CF adolescents and uncoupling of bone balance in adults. 1,25(OH)2D was weakly correlated with OC in CF children ( r=0.43, P=0.01), and with tDpd in CF and control adolescents ( r=0.33, P=0.05 and r=0.36, P=0.02, respectively); thus there was limited evidence of association of calcitropic hormones, which had an abnormal pattern in all age groups, with bone turnover. There was no association between calcitropic hormones or bone turnover markers and LS BMD z-score. Despite vitamin D sufficiency, abnormalities of calcium metabolism and bone turnover markers were still apparent and bone accretion was decreased relative to resorption in the CF adolescent and adult groups. These changes were not fully explained by disease severity or genotype, but are consistent with reports of decreased BMD and unique bone histomorphometry in older subjects with CF.