ORCID Profile
0000-0003-0579-3452
Current Organisations
Sydney Children’s Hospitals Network
,
The University of Auckland
,
Royal Australasian College of Physicians
,
University of Sydney
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Publisher: AMPCo
Date: 03-2003
DOI: 10.5694/J.1326-5377.2003.TB05165.X
Abstract: Three children presented with adrenal crises, manifested by vomiting and hypoglycaemia, after protracted courses of high-dose inhaled corticosteroids for asthma. Significant dose reduction was possible in all three without loss of asthma control, emphasising the importance of back-titration to minimise dose. Parents of children taking high doses of inhaled corticosteroids should be alerted to the clinical features of adrenal insufficiency. If suspected, prompt medical assessment should be arranged, including serum glucose and cortisol measurement.
Publisher: Wiley
Date: 08-09-2006
DOI: 10.1111/J.1440-1754.2006.00948.X
Abstract: C s are an important part of diabetic management in children yet data on the safety and efficacy of c s are limited. We assessed the safety and efficacy of blood glucose management guidelines at summer c s for diabetic children. Consistent management guidelines were implemented during 10 consecutive diabetes c s held in the same facility between 1998 and 2002. Using the entire s le of c ers aged 9-13 years, we analysed insulin dosage alterations, the frequency of hypoglycaemia ( 15 mmol/L) and ketosis and evaluated our overnight management guidelines. The effects of sex, year, age, insulin regimen and duration of diagnosis on hypoglycaemia frequency were determined. Mean insulin doses decreased 19.2% (95% confidence interval 16.9-21.6%) by the last day of c (day 6) relative to the day prior to c . Mean blood glucose levels were 11.4 mmol/L before breakfast and the main evening meal, 11.3 mmol/L before bed, 10.8 mmol/L at midnight and 9.4 mmol/L at 3 am. Of the 10 839 readings analysed, 984 (9.1%) were below 4 mmol/L (0.5 per c er/day) with no clinical grade 3 (seizure or coma) hypoglycaemia. Hypoglycaemia frequency was independent of sex, year, age, insulin regimen and duration of diagnosis (all P > 0.05). There were 2570 (23.7%) readings above 15 mmol/L (1.4 per c er/day) but only 42 (0.4%) were associated with significant ketosis. Children at diabetes c s experience considerable blood glucose variability however, the careful application of monitoring and management guidelines can avoid serious adverse events.
Publisher: Wiley
Date: 31-05-2021
DOI: 10.1111/IMJ.15426
Abstract: The goal of therapy in type 1 diabetes (T1D) is to achieve optimal glycaemic targets and reduce complications. Robust data representing glycaemic outcomes across the lifespan are lacking in Australasia. To examine contemporary glycaemic outcomes and rate of use of diabetes technologies in Australasian people with T1D. Cross-sectional analysis of de-identified data from 18 diabetes centres maintained in the Australasian Diabetes Data Network registry during 2019. Glycaemia was measured using glycated haemoglobin (HbA1c). The proportion of people with T1D achieving the international HbA1c target of <53 mmol/mol (7%) was calculated. Rates of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were determined. A total of 7988 in iduals with T1D with 30 575 visits were recorded in the registry. The median (interquartile range) age was 15.3 (10.0) years and diabetes duration was 5.7 (9.4) years with 49% on multiple daily injections (MDI) and 36% on CSII. The mean HbA1c for the whole cohort was 66 mmol/mol (8.2%). HbA1c increased with age, from 60 mmol/mol (7.6%) in children <10 years, increasing during adolescence and peaking at 73 mmol/mol (8.8%) in the 20-25 years age group. The HbA1c target of <53 mmol/mol (7%) was met in 18% of children and 13% of adults. HbA1c was lower on CSII as compared with those on MDI (P < 0.0001). Only a minority of children and adults achieve the recommended glycaemic goals despite access to specialist care in major diabetes centres. There is a need to identify factors that improve glycaemic outcomes.
Publisher: AMPCo
Date: 03-2004
Publisher: American Diabetes Association
Date: 30-11-2018
DOI: 10.2337/DC17-1604
Abstract: 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. 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). 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, In children and adolescents with type 1 diabetes, PLGM reduced hypoglycemia without deterioration in glycemic control.
Publisher: BMJ
Date: 10-2016
Publisher: American Diabetes Association
Date: 07-2006
DOI: 10.2337/DC05-2315
Abstract: OBJECTIVE—This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine. RESEARCH DESIGN AND METHODS—Pediatric subjects were recruited if they had an HbA1c (A1C) & % and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group. RESULTS—There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (−0.4% [95% CI −0.7 to −0.1]) and the control group (−0.4% [−0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia. CONCLUSIONS—CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting.
Publisher: Wiley
Date: 15-05-2012
DOI: 10.1111/J.1440-1754.2012.02465.X
Abstract: In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with 'idiopathic' short stature are not 'short, normal children' and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost-effective in idiopathic short-stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment.
Publisher: Elsevier BV
Date: 09-2002
Abstract: The predominant influences on fetal growth are maternal and placental factors. Post-natal growth is regulated by a complex interaction between genetic, environmental and hormonal influences. The role of the growth hormone insulin-like growth factor (GH-IGF) system is explored, including the emerging role of IGF-2 in fetal growth. Increasing understanding of the genetics of overgrowth and short stature syndromes is contributing greatly to basic understanding of growth regulation. A range of prenatal overgrowth syndromes is discussed, including those associated with neonatal hyperinsulinism and hypoglycaemia.Post-natal overgrowth may be caused by a erse range of normal variant conditions, endocrine disorders, chromosomal abnormalities and other genetic syndromes. An approach to diagnosis is presented and major conditions discussed in detail. Sex-steroid therapy for height limitation continues to be a controversial area with uncertainty about height prediction, benefits achieved and possible long-term side-effects.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2022
Publisher: Bioscientifica
Date: 05-1996
Abstract: Somatostatin has been suggested to influence the somatotrophic axis outside the central nervous system, in reducing GH-induced IGF-I mRNA and IGF-I generation. This study aimed to determine whether such effects were mediated via the GH receptor (GHR). GH-deficient dwarf rats aged 45–47 days ( n =8 per group) received twice daily subcutaneous injections of octreotide (1 mg/kg) (group O), saline (group S), octreotide (1 mg/kg) plus bovine GH (0·25 mg/kg) (group OG), or bovine GH (0·25 mg/kg) plus saline (group G) for 10 days. Octreotide-treated animals had less weight gain compared with saline-treated animals, but not when GH cotreated (group OG vs G). Octreotide had an overall effect on decreasing length gain ( P ·01). Serum IGF-I (ng/ml) was reduced by octreotide (group O 171 ±11, group S 239 ± 20, P ·01 group OG 283 ± 30, group G 362 ± 10, P ·001), as was serum insulin ( P ·001). A significant decrease in hepatic and muscle IGF-I mRNA expression was found as expected, yet this was not associated with decreased hepatic GHR expression. Rather, an increase in hepatic 125 I-bovine GH specific binding was observed ( P ·001) and, in GH-cotreated animals (OG), hepatic GHR and GH binding protein (GHBP) mRNA expression were also increased by octreotide by approximately 40%. In muscle, octreotide was associated with an approximately 30% decrease in GHBP mRNA and no effect on GHR mRNA. This study suggests that the suppressive effects of octreotide on IGF-I metabolism, at least in liver, are not mediated via down-regulation of GHR expression, but more likely by direct effects on IGF-I expression. Journal of Endocrinology (1996) 149, 223–231
Publisher: Springer Science and Business Media LLC
Date: 2003
DOI: 10.2165/00128072-200305070-00005
Abstract: Inhaled corticosteroids (ICS) remain a vital part of the management of persistent asthma, but concerns have been raised about their potential adverse effects in children. This review examines the safety data on three new ICS - fluticasone propionate, mometasone, and extrafine beclomethasone in hydrofluoroalkane (HFA-134a) propellant (QVAR The use of tradenames is for product identification purposes only and does not imply endorsement. formulation) in relation to the older corticosteroids. Topical adverse effects such as thrush and dysphonia are rare, but dental erosion is a possibility with powder forms of ICS because of their low pH. Thus, it is important to stress mouth rinsing after administration and maintaining good dental hygiene to minimize this risk. Biochemical adrenal suppression can be readily demonstrated, particularly with high doses of all ICS. The clinical relevance of this was uncertain in the past, but there have now been >50 reported cases of acute adrenal crises in children receiving ICS, most of whom were on fluticasone propionate. In order to minimize the risk of symptomatic adrenal suppression, it is important to back-titrate the ICS dose and alert families of children receiving high-dose ICS of this potential adverse effect. A pediatric endocrine opinion should be sought if adrenal suppression is suspected. The older ICS cause temporary slowing of growth velocity, but the limited data available do not show any significant compromise of final adult height. The effect on growth of fluticasone propionate may not be as great as with the older ICS, but the studies have been short term and only used low doses of fluticasone propionate. There have been case reports of growth suppression in children receiving high doses of fluticasone propionate. The limited studies performed on the effect of ICS on bone mineral density in children did not show any adverse effects, but there may be an increased risk of fractures. Hydrofluoroalkane beclomethasone (QVAR) is essentially the same drug as chlorofluorocarbon beclomethasone, but with double the lung deposition owing to the smaller particle size. Thus, it could be expected that any adverse effects seen with chlorofluorocarbon beclomethasone would be the same with hydrofluoroalkane beclomethasone. However, some of the published data, particularly in adults, suggest that hydrofluoroalkane beclomethasone may be less systemically active than chlorofluorocarbon beclomethasone, even at equipotent doses. As yet, there are no long-term data on mometasone, but initial studies in adults suggest there may be less suppression of the hypothalamic-pituitary-adrenal axis, although further studies are required, particularly in children.ICS will remain a cornerstone in the management of persistent pediatric asthma, provided that the diagnosis of asthma is secure. It is very important to use ICS appropriately and to ensure the lowest possible doses are used to achieve symptom control, thus minimizing the risk of serious adverse effects.
Publisher: American Diabetes Association
Date: 03-2008
DOI: 10.2337/DC07-2209
Publisher: Wiley
Date: 20-07-2017
DOI: 10.1111/JPC.13631
Abstract: 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. 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. 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. 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.
Publisher: Wiley
Date: 17-12-2020
DOI: 10.1111/JPC.14722
Abstract: 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. 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
Publisher: Wiley
Date: 18-09-2013
DOI: 10.1111/CEN.12315
Abstract: To compare weight (per kg)- vs body surface area (BSA, per m(2) )-based growth hormone (GH) dosing formats in children and to derive a useful conversion formula between the two formats. Growth hormone doses (>33,000) from 1874 children were obtained from the national Australian database (OZGROW) and used to derive conversion formulae and to confirm the accuracy of a conversion formula based on a weight-only BSA estimate. A further 27,000 doses were used to test the accuracy of all formulae. The best conversion formula was used to compare weight- and surface area-based GH dosing, which included an analysis of first year response (∆SDS height or growth velocity, GV). Growth hormone doses in mg/m(2) /wk and mg/kg/wk, dose estimates, residuals, first year ∆SDS, first year GV. The formula, [Formula: see text] based on a weight-only BSA estimate, provides accurate dose conversion (mean residual, 0·005 mg/kg/week). A constant mg/m(2) /week dose expressed in terms of mg/kg/week declines quickly with increasing body weight to approximately 15 kg after which the decline continues although less dramatically. For Australian patients, despite an increase in mean per m(2) dose with increased starting weight/age, the per kg dose decreased. This was associated with a greater decline in first year GV than estimated if a per kg dose had been maintained. Growth hormone doses can be accurately converted between formats. Surface area-based GH dosing is likely to result in a reduced height response as children become heavier when compared with weight-based GH dosing.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Medknow
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 29-07-2019
Publisher: American Academy of Pediatrics (AAP)
Date: 07-2007
Abstract: OBJECTIVES. Studies of adults have shown that thrice-daily hydrocortisone dosing results in more physiologic cortisol profiles than twice-daily dosing. There are no data on thrice-daily dosing and only limited data on twice-daily dosing in children despite the possible adverse effects of glucocorticoid underreplacement or overreplacement. METHODS. Using 24-hour cortisol and glucose profiles, along with computerized cognitive testing, our aim was to assess prescribed hydrocortisone regimens in children and adolescents with hypopituitarism. RESULTS. Twenty patients with adrenocorticotrophic hormone deficiency participated. The hydrocortisone dosing regimen was thrice daily in 9 patients and twice daily in 11 patients (mean total daily dose: 8.3 ± 2.6 and 7.6 ± 2.1 mg/m2 per day, respectively). Those on twice-daily dosing had more waking hours (between 8:00 am and 8:00 pm) below the reference range than those on thrice-daily dosing (5.5 vs 2.1) and more daytime prolonged hypocortisolemia, defined as plasma cortisol level of & nmol/L for ≥4 hours (64% vs 0%). Morning doses & mg/m2 caused larger postdose peaks than & mg/m2 (151 vs 47 nmol/L, above the 97.5th percentile). However, there was no difference in the length of time taken to reach nadir below the 2.5th percentile (5.2 vs 4.8 hours). This was true for evening doses of & .5 mg/m2 and & 2.5 mg/m2. No hypoglycemia or hyperglycemia was detected in association with low or high cortisol levels. On predose and postdose cognitive testing (34 paired tests), no significant change in reaction speed was detected (453.3 vs 438.8 milliseconds) or in subgroup analysis of those who had symptoms of lethargy, predose cortisol levels of & nmol/L, or prolonged hypocortisolemia. CONCLUSIONS. Thrice-daily dosing resulted in less frequent and prolonged hypocortisolemia than twice-daily regimens, but we were unable to relate either regimen to acute clinical end points of glycemia, lethargy, or cognitive function.
Publisher: Wiley
Date: 12-1999
DOI: 10.1046/J.1365-2265.1999.00877.X
Abstract: The Ati Negritos are a Pygmy-like aboriginal population from the Philippines with physical characteristics of short stature, dark skin and woolly, kinked hair. Their final height, components of their GH-IGF axis and various nutritional markers are described. SUBJECTS, DESIGN AND MEASUREMENTS: Auxological data and sera for the components of the GH-IGF axis and nutritional parameters were collected from 9 adult Ati Negritos in their native environment and 10 Filipinos in Sydney. The height SDS (- 3.66 +/- 1.1 vs. - 1.01 +/- 1.2), weight SDS (- 2.30 +/- 1.6 vs. 0.10 +/- 0.7), and BMI SDS (- 1.4 +/- 1.8 vs. - 0.2 +/- 0.5) between the two groups were significantly different (P < 0.01). The mean height of the 6 male Ati Negritos was 149 +/- 7 and 144 +/- 3 cm for the females and are comparable with the African Pygmies and the Mountain Ok people of Papua New Guinea. The Ati Negritos showed lower growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), acid labile subunit (ALS), zinc, albumin, ferritin, iron, iron saturation and much higher insulin-like growth factor binding protein 2 (IGFBP-2) and plasma transferrin concentrations. No differences were noted in random growth hormone (GH), plasma insulin-like growth factor II (IGF-II), nor in their plasma concentrations of prealbumin, thyroid stimulating hormone (TSH) and free thyroxine (T4). Perturbations of both the GH-IGF-I axis and nutritional markers exist in the Ati Negritos. These findings may be determinants of their stature however, the aetiology of these changes remains to be fully elucidated.
Publisher: Springer Science and Business Media LLC
Date: 10-1996
DOI: 10.1007/BF02282833
Publisher: The Endocrine Society
Date: 06-2006
DOI: 10.1210/JC.2006-0241
Abstract: Metformin therapy for adults and children with type 2 diabetes is well established. However, its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined. We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity. Patients referred to a pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover trial. Twenty-eight patients (13 males) aged 9-18 yr participated in the study. Patients received metformin (1 g twice daily) and placebo for 6 months, each with a 2-wk washout period. Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal magnetic resonance imaging), and insulin sensitivity (Si minimal model, fasting insulin and glucose) were measured at baseline and 6 and 12 months. Mean age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score 2.54 (range, 1.93-2.85). Metformin had a greater treatment effect over placebo for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in 45% of subjects while on metformin and 27% of subjects while on placebo (P = 0.21). Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin. Although improvement in Si was noted in many in iduals, Si was a less useful parameter for analysis of group data, possibly because of effects of variable compliance and changing Si during puberty.
Publisher: Walter de Gruyter GmbH
Date: 09-04-2016
Abstract: 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. Endocrine patients provided plasma and saliva for estradiol (females) or testosterone (males) assay. Saliva s les were also tested with a blood contamination kit. 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 .001). A significant number of saliva s les had blood contamination. After exclusion, correlations remained non-significant for estradiol, but strengthened for testosterone (r=0.88, p .001). 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.
Publisher: Wiley
Date: 22-06-2014
DOI: 10.1111/JPC.12672
Abstract: (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. 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. 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. 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.
Publisher: Wiley
Date: 03-03-2010
DOI: 10.1111/J.1365-2265.2009.03677.X
Abstract: 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. Retrospective review. 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. Oral glucose tolerance test. 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. Fasting glucose and insulin levels should be measured in young people with insulin resistance before undertaking a time- and resource-intensive OGTT.
Publisher: Cold Spring Harbor Laboratory
Date: 22-06-2023
DOI: 10.1101/2023.06.21.546027
Abstract: Mass spectrometry imaging (MSI) has accelerated the understanding of lipid metabolism and spatial distribution in tissues and cells. However, few MSI studies have approached lipid imaging quantitatively and those that have focus on a single lipid class. Herein, we overcome limitation of quantitative MSI (Q-MSI) by using a multi-class internal standard lipid mixture that is sprayed homogenously over the tissue surface with analytical concentrations that reflects endogenous brain lipid levels. Using this approach we have performed Q-MSI for 13 lipid classes representing sum-composition lipid species. This was carried out using both MALDI (negative ion mode) and MALDI-2 (positive ion mode) and pixel-wise normalisation of each lipid species signal to the corresponding class-specific IS an approach analogous to that widely used for shotgun lipidomics from biological extracts. This approach allows pixel concentrations of lipids to be reported in pmol/mm 2 . Q-MSI of lipids covered 3 orders of magnitude in dynamic range and revealed subtle change sin in distribution compared to conventional total-ion-current normalisation approaches. The robustness of the method was evaluated by repeating experiments in two laboratories on biological replicates using both timsTOF and Orbitrap mass spectrometers operated with a ~4-fold difference in mass resolution power. There was a strong overall correlation in the Q-MSI result obtained using the two approaches with outliers mostly rationalised by isobaric interferences that are only resolved with the Orbitrap system or the higher sensitivity of one instrument for particular lipid species, particularly for lipids detected at low intensity. These data provide insight into how mass resolving power can affect Q-MSI data. This approach opens up the possibility of performing large-scale Q-MSI studies across numerous lipid classes and reveal how absolute lipid concentrations vary throughout and between biological tissues.
Publisher: Hindawi Limited
Date: 22-05-2015
DOI: 10.1111/PEDI.12285
Abstract: To characterize current insulin pump settings used in young patients with type 1 diabetes mellitus (T1DM) and to assess their relationship to glycemic control. This retrospective study included patients aged 1 yr using a Medtronic pump device. Pump data including number of blood glucose (BG) tests per day, basal and bolus insulin parameters, carbohydrate ratio (CR), and insulin sensitivity factors (ISFs) were averaged over 14 d for statistical analyses. Anthropometric data and recent glycosylated hemoglobin A1c (HbA1c) were recorded. A total of 292 patients (144 males and 148 females) were included in the study. Participants had a median age (interquartile range, IQR) of 12.9 yr (10.0-15.1 yr) and pump duration of 2.8 yr (1.5-4.2 yr). No significant differences in median HbA1c (IQR) were observed in preschool [n = 14 HbA1c 7.8% (7.3-8.3%)], prepubertal [n = 105 HbA1c 8.1% (7.7-8.9%)], and adolescent subjects [n = 173 HbA1c 8.4% (7.7-9.0%)]. Adolescents took significantly fewer boluses and BG tests per day compared with younger children (p < 0.05). Age-specific diurnal variation in basal insulin delivery was noted. Additionally, stronger carbohydrate cover and weaker corrections were used in real-life compared with theoretical 500 and 100 rules, respectively. Lower HbA1c was associated with higher number of daily boluses, greater number of BG tests per day, lower average CR/500 rule ratio, and higher average ISF/100 rule ratio adjusted for age (R(2) = 0.22 p < 0.01). Insulin pump therapy requires continuous adjustments and glycemic targets are achieved by a minority. We believe this is the first study in pediatric cohort looking at association between CR and ISF with glycemic control.
Publisher: Wiley
Date: 02-1993
Publisher: Hindawi Limited
Date: 09-2000
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
Publisher: Wiley
Date: 06-06-2012
DOI: 10.1111/J.1365-2265.2011.04230.X
Abstract: 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. 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). 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. Australian BGHD, SSSG-ISS and SSSG-FSS patients who had completed 1, 2, or 3 years of treatment and were currently receiving GH. Growth hormone dose, change in height-standard deviation score (ΔSDS) and growth velocity (GV). 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. 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.
Publisher: Wiley
Date: 11-01-2021
DOI: 10.1111/JPC.15349
Abstract: Paediatric hypoglycaemia often requires specific investigations to determine aetiology. S les 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. 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. 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. 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.
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/IMJ.13943
Abstract: Growth hormone (GH) replacement therapy was recently recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the Pharmaceutical Benefits Scheme for adults with severe GH deficiency and impaired quality of life. This approval was significant for two reasons. First, the application was initiated and coordinated by a health professional working group, who prepared a 'public interest' submission to PBAC. Second, it resulted in a recommendation to subsidise therapy for a rare disease after two prior rejections on the basis of uncertainty about efficacy and cost effectiveness. There are important lessons to learn about the power of professional groups to drive health policy and attain funding for rare diseases.
Publisher: The Endocrine Society
Date: 05-2013
DOI: 10.1210/JC.2012-4251
Abstract: Prediabetes and clinical insulin resistance in adolescents are rapidly emerging clinical problems with serious health outcomes. The objective of this study was to determine the efficacy of 2 structured lifestyle interventions, both differing in diet macronutrient composition, on insulin sensitivity. 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 included overweight or obese 10- to 17-year-olds with either prediabetes and/or clinical features of insulin resistance. 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. The outcomes included an insulin sensitivity, anthropometry, and cardiometabolic profile at 6 months. 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. 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.
Publisher: Walter de Gruyter GmbH
Date: 1999
DOI: 10.1515/JPEM.1999.12.3.433
Abstract: We aimed to assess the growth, diabetes control, dietary intake and compliance with a gluten-free diet in children with insulin dependent diabetes mellitus (IDDM) and coeliac disease in a major paediatric and adolescent diabetes clinic. Children with IDDM and biopsy-proven coeliac disease aged <18 years were included and compared with IDDM controls matched for age, sex and duration of diabetes. Twenty patients with coeliac disease and IDDM participated (15 female, age 7.4-17.3 yr), with two matched IDDM controls for each (age 6.9-17.4 yr). The prevalence of coeliac disease in this diabetes clinic population was 2.6%. All patients completed a 3 day food record (3DFR) and a 7 day food frequency questionnaire (FFQ) to assess dietary intake and gluten-free compliance. Diabetes control measured by HbA1c was not different between groups or compared to the overall clinic population (8.48 +/- 0.98% for coeliac patients vs 8.87 +/- 1.46 for IDDM controls vs 8.60 +/- 1.30 for overall clinic population aged 5.0-17.9 yr). Height, weight and BMI standard deviation scores were not different between coeliac patients and IDDM controls. No clinically significant differences were found in intake of energy, macronutrients or micronutrients. The proportion of energy intake from carbohydrate, protein and fat was within recommended ranges, except for a higher saturated fat intake. Only 30% of coeliac patients complied with a strict gluten-free diet, but growth parameters were unaffected by dietary compliance. Thus, we found that children and adolescents with coexisting IDDM and coeliac disease have normal growth, equivalent diabetes control and no differences in energy or nutrient intake compared to matched IDDM controls in our clinic population.
Publisher: American Medical Association (AMA)
Date: 12-2021
Publisher: American Academy of Pediatrics (AAP)
Date: 07-2015
Abstract: Prevalence rates of type 1 diabetes (T1D) and celiac disease (CD) vary from 1.6% to 16.4% worldwide. Screening guidelines are variable and not evidence based. Our aim was to conduct a systematic review of CD in T1D. Medline, Embase, and the Cochrane Library were searched. Studies were limited to those in English and in humans. We selected longitudinal cohort studies screening for CD in T1D with at least 5 years of follow-up. Screening rates, characteristics, and prevalence of biopsy-proven CD in people with T1D were extracted. We identified 457 nonduplicate citations 48 were selected for full-text review. Nine longitudinal cohort studies in 11 157 children and adolescents with 587 cases of biopsy-proven CD met the inclusion criteria. Median follow-up was 10 years (range: 5–18 years). The weighted pooled prevalence of CD was 5.1% (95% confidence interval: 3.1–7.4%). After excluding 41 cases with CD onset before T1D, CD was diagnosed in 218 of 546 (40%) subjects within 1 year, in 55% within 2 years, and in 79% within 5 years of diabetes duration. Two studies (478 cases) reported higher rates of CD in children aged & years at T1D diagnosis. The duration of follow-up varied across the included studies. CD screening frequency progressively decreased with increased T1D duration. Because most cases of CD are diagnosed within 5 years of T1D diagnosis, screening should be considered at T1D diagnosis and within 2 and 5 years thereafter. CD screening should be considered at other times in patients with symptoms suggestive of CD. More research is required to determine the screening frequency beyond 5 years of diabetes duration.
Publisher: Cold Spring Harbor Laboratory
Date: 17-05-2019
DOI: 10.1101/637892
Abstract: Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response can only account for up to 60% of the variance. The aim of this work was to take a novel genomic approach to growth prediction. GHD (n=71) and TS patients (n=43) were recruited in a study on the long term response to r-hGH over five years of therapy. Pharmacogenomic analysis was performed using 1219 genetic markers and baseline blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria required for predictive value. However, we demonstrated that transcriptomic data can be used to predict growth with a high accuracy (AUC 0.9) for short and long term therapeutic response in GHD and TS. Network models identified an identical core set of genes in both GHD and TS at each year of therapy whose expression can be used to classify therapeutic response to r-hGH. Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. We have characterised the utility of baseline transcriptome for the prediction of growth response including the identification of a set of common genes in GHD and TS. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. A blood transcriptome signature predicts response to recombinant human growth hormone in both growth hormone deficient and Turner syndrome children Trial registration numbers: NCT00256126 & NCT00699855
Publisher: Wiley
Date: 30-10-2014
DOI: 10.1111/DME.12329
Abstract: There are conflicting data on microvascular complications in coexisting Type 1 diabetes and coeliac disease. We compared complications rates in youth with or without coeliac disease and examined the association between gluten-free diet adherence and complications. This was a comparative study of adolescents (2510 without coeliac disease, 129 with coeliac disease) 60 (47%) did not adhere to a gluten-free diet--defined as elevated anti-tissue transglutaminase or endomysial immunoglobulin A titres. Retinopathy was detected using 7-field fundal photography and albumin excretion rate by timed overnight urine collections, with early elevation defined as albumin excretion rate ≥ 7.5 μg/min. Logistic regression was used to examine the association between complications and explanatory variables, including coeliac disease vs. no coeliac disease, gluten-free diet adherence vs. non-adherence, diabetes duration and HbA1c . Median age at last assessment was 16.5 years. Those with coeliac disease vs. those without were younger at diabetes diagnosis (7.1 vs. 8.6 years, P < 0.001) and had longer diabetes duration (9.3 vs. 7.2 years, P < 0.001). HbA1c was lower in those with coeliac disease vs. those without (67 vs. 70 mmol/mol, 8.3 vs. 8.6%, P = 0.04) and adherence to a gluten-free diet vs. non-adherence (66 vs. 72 mmol/mol, 8.2 vs. 8.7%, P = 0.003). There were no differences in complication rates between those with coeliac disease vs. those without (retinopathy 22 vs. 23%, elevated albumin excretion rate 31 vs. 28%). Non-adherence to a gluten-free diet was associated with elevated albumin excretion rate (40 vs. 23%, P = 0.04). In multivariable logistic regression, elevated albumin excretion rate was associated with non-adherence to a gluten-free diet (odds ratio 2.37, 95% CI 1.04-5.40, P = 0.04) and diabetes duration (odds ratio 1.13, 95% CI 1.02-1.25, P = 0.03), but not HbA1c . While glycaemic control is better in patients with coeliac disease, non-adherence to a gluten-free diet is associated with elevated albumin excretion rate. The possible protection of a gluten-free diet on complications warrants further investigation.
Publisher: American Academy of Pediatrics (AAP)
Date: 12-2006
Abstract: Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges however, fludrocortisone therapy can be an effective adjunct to treatment.
Publisher: Bioscientifica
Date: 08-1993
Abstract: Insulin-like growth factor-II (IGF-II) binding in the growing tip of the deer antler was examined using autoradiographical studies, radioreceptor assays and affinity cross-linking studies. Antler tips from red deer stags were removed 60 days after the commencement of growth, and cryogenically cut into sections. Sections were incubated with radiolabelled IGF-II, with or without an excess of competing unlabelled IGF-II and analysed autoradiographically. Radiolabelled IGF-II showed high specific binding in the reserve mesenchyme and perichondrium zones, which are tissues undergoing rapid differentiation and cell ision in the antler. Binding to all other structural zones was low and significantly ( P ·001) less than binding to the reserve mesenchyme erichondrium zones. Radioreceptor assays on antler microsomal membrane preparations revealed that the IGF-II binding was to a relatively homogeneous receptor population ( K d = 1·3 × 10 −10 mol/l) with characteristics that were not entirely consistent with those normally attributed to the type 2 IGF receptor. Tracer binding was partly displaceable by IGF-I and insulin at concentrations above 10 nmol/l. However, affinity cross-linking studies revealed a single band migrating at 220 kDa under non-reducing conditions, indicative of the type 2 IGF receptor. These results indicate that, in antler tip tissues, IGF-II binds to sites which have different binding patterns and properties from receptors binding IGF-I. This may have functional significance as it appears that, whilst IGF-I has a role in matrix development of cartilage, IGF-II may have a role in the most rapidly differentiating and proliferating tissues of the antler. Journal of Endocrinology (1993) 138, 233–241
Publisher: AMPCo
Date: 09-2006
Publisher: Hindawi Limited
Date: 21-12-2021
DOI: 10.1111/PEDI.13169
Publisher: Springer Science and Business Media LLC
Date: 27-05-2021
DOI: 10.1038/S41397-021-00237-5
Abstract: Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD ( n = 71) and TS patients ( n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2010
Publisher: Wiley
Date: 08-10-2007
DOI: 10.1111/J.1365-2265.2007.03100.X
Abstract: The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed. To compare the ability of the hCRH test, LDST, 9am cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric population. A cross-sectional study in a tertiary paediatric endocrine clinic. Thirty-one children and adolescents (aged 2.3-18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h cortisol profile performed. Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol or = 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (> or = 140 nmol/l). The 24-h cortisol area under the curve (AUC) for these patients was within the 10th-90th percentiles for control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r = 0.88, P = 0.01), with no difference between the peaks (mean difference -5.3 nmol/l, P = 0.69). In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.
Publisher: Wiley
Date: 30-06-2019
DOI: 10.1111/JPC.14546
Publisher: Bioscientifica
Date: 07-1996
Abstract: The majority of IGF-I circulates in a large (150 kDa) ternary complex with IGF-binding protein-3 (IGFBP-3) and a non-IGF-binding acid-labile subunit. The secretion of ternary complex into the circulation from liver has been considered to be GH-dependent however, recent data indicate that GH does not directly regulate hepatic IGFBP-3 synthesis. To examine the role of insulin in regulating plasma IGFBP-3 levels, postpubertal male GH-deficient ( dw / dw ) rats were treated every 8 h with injections (s.c.) of 0·9% saline, 20 μg insulin/day, 200 μg hIGF-I/day, or 20 μg insulin/day plus 200 μg hIGF-I/day, for 10 days with the animals being killed 2–3 h after the final injection. Hypoglycaemia was not observed in any of the treatment groups. hIGF-I treatment increased longitudinal growth and weight gain ( P ·05), while insulin treatment had no effect. Plasma IGF-I levels were increased in groups treated with hIGF-I ( P ·05), while insulin treatment resulted in a reduction ( P -05): saline=267·1 ± 15·6 (ng/ml ± s.e.m. ), insulin=219·3 ± 17·5, hIGF-I=391·7 ± 17·6, insulin plus hIGF-I=357·5 ± 31·8. Hepatic IGF-I mRNA expression was increased in insulin-treated dw / dw rats in comparison with hIGF-I-treated animals ( P ·05) but not in comparison with saline control or the combined treatment groups. Plasma levels of intact IGFBP-3, measured by ligand blot analysis, were increased in all treatment groups compared with saline ( P ·05): saline=100·0 ± 9·4% (% of saline ± s.e.m. ), insulin=149·9 ± 17·5%, hIGF-I= 191·4 ± 17·3%, insulin plus hIGF-I=205·4 ± 15·3%. The levels of the 28/32 kDa IGFBPs and IGFBP-4 in plasma were increased by hIGF-I treatment ( P ·05) but not by insulin treatment. Hepatic specific 125 I-bovine GH binding was not significantly different in any of the treatment groups. This study provides the first evidence in non-diabetic animals that insulin regulates hepatic IGF-I mRNA expression, plasma IGF-I and plasma IGFBP-3 levels in the GH-deficient state without changes in hepatic GH receptors. The ergent response of plasma IGF-I and IGFBP-3 levels to insulin treatment in the present study may indicate an effect of insulin on the clearance of IGF-I from the circulation. Journal of Endocrinology (1996) 150, 67–76
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000502231
Abstract: The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JPEDS.2016.08.105
Abstract: To evaluate quality of life (QoL) and glycemic control in youth with type 1 diabetes (T1D) and celiac disease vs T1D only. We hypothesized that QoL scores would be lower in youth with T1D and celiac disease and those nonadherent to the gluten-free diet (GFD). This case control study included 35 youth with T1D and 35 with T1D and celiac disease matched for age, sex, diabetes duration, and hemoglobin A1c level. QoL was assessed in participants and parents using the Pediatric Quality of Life Inventory Generic Core Scale, Pediatric Quality of Life Inventory Diabetes Module. and the General Well-Being Scale youth with T1D and celiac disease also completed the celiac disease-specific DUX questionnaire and parents completed the Pediatric Quality of Life Inventory Family Impact Scale. Questionnaires were scored from 0 to 100 higher scores indicate better QoL or well-being. Scores were compared between T1D vs T1D with celiac disease, with subgroup analysis by GFD adherence vs nonadherence and therapy (continuous subcutaneous insulin infusion vs multiple daily injections). Youth with T1D and celiac disease reported similar generic and diabetes-specific QoL to T1D only. GFD nonadherent vs adherent youth reported lower diabetes-specific QoL (mean score 58 vs 75, P = .003) and lower general well-being (57 vs 76, P = .02), as did their parents (50 vs 72, P = .006), and hemoglobin A1c was higher (9.6% vs 8.0%, P = .02). Youth with T1D and celiac disease using continuous subcutaneous insulin infusion vs multiple daily injections had similar generic and diabetes-specific QoL and A1C (8.6 vs 8.2%, P = .44), but were less happy having to follow a lifelong diet (59 vs 29, P = .007). Youth with T1D and celiac disease who do not adhere to the GFD have lower QoL and worse glycemic control. Novel strategies are required to understand and improve adherence in those with both conditions.
Publisher: Wiley
Date: 24-09-2008
Publisher: Mary Ann Liebert Inc
Date: 06-2021
Publisher: Wiley
Date: 1991
Publisher: The Endocrine Society
Date: 12-2010
DOI: 10.1210/JC.2010-0647
Abstract: Introduction: It has been postulated that central adrenal insufficiency (CAI), resulting from hypothalamic dysfunction, may contribute to the increased unexplained death rates in Prader Willi syndrome (PWS). A study using the overnight metyrapone test reported a 60% prevalence of CAI in children with PWS. We used a low-dose Synacthen test to screen for CAI in children with PWS. Methods: We studied 41 children with genetic diagnosis of PWS [20 males mean age, 7.68 (±5.23) yr] in five pediatric endocrinology centers in Australasia. All participants were randomly selected, and none had a history of Addisonian crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving GH, and four were receiving T4. Their mean body mass index z-score was +1.48 (±1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv administration of 1 μg Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal. Results: The mean baseline ACTH and cortisol were 15 (±14) ng/liter and 223 (±116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (±114) nmol/liter, and the average increase from baseline was 201%. Conclusions: Our result suggests that CAI is rare in children with PWS.
Publisher: Walter de Gruyter GmbH
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 25-04-2009
DOI: 10.1007/S00125-009-1365-0
Abstract: The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic ( or =10.1 mmol/l) ranges and glycaemic variability. Sixty-two participants were recruited and randomised 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75% p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72 95% CI -5.37 to 8.81), hypoglycaemic (0.54 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use or =70%) was not universally acceptable. ACTRN12606000049572
Publisher: Mary Ann Liebert Inc
Date: 02-2015
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.DIABRES.2019.107989
Abstract: Improved frequency of sensor use improves glycaemic control. Furthermore, there is no deterioration of glycaemic control with increased sensor use in in iduals on Predictive Low Glucose Management (PLGM) system. Younger children are more likely to have better sensor uptake than older children.
Publisher: S. Karger AG
Date: 1993
DOI: 10.1159/000183791
Abstract: To further evaluate the role of growth hormone (GH) in the neonatal period, the effects of GH or insulin-like growth factor 1 (IGF-1) administration were studied in the neonatal GH-deficient rat. Groups of pups from newborn litters were randomized to receive twice daily subcutaneous injections of recombinant bovine growth hormone (bGH, 5 micrograms), recombinant human IGF-1 (10 micrograms) or saline from the second to twelfth day of life. The effects on growth parameters, serum IGF-1 concentration, body composition and hepatic GH receptor binding were assessed. bGH-treated animals showed increases in body weight gain (p = 0.01), serum IGF-1 (p < 0.01), carcass nitrogen (p < 0.001) and carcass water (p < 0.001) compared to IGF-1 or saline-treated animals. No differences in these parameters were noted between IGF-1 and saline-treated groups. bGH-treated animals showed a significantly lower hepatic GH receptor binding (p < 0.01) compared to the other two groups. The demonstration of anabolic responses to GH administration in the neonatal period has implications for the possible role of GH in fetal and neonatal growth.
Publisher: BMJ
Date: 04-2016
Publisher: Springer Science and Business Media LLC
Date: 22-03-2022
DOI: 10.1007/S00431-022-04439-2
Abstract: In iduals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of in iduals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for in iduals with PWS (including 22 males) aged 4.4–24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28% β = 0.028 p 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29% β = 0.023 p = 0.007). This relationship was not moderated by BMI Z -scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years. Conclusions : These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children. What is Known: • In iduals with Prader-Willi syndrome (PWS) commonly experience excessive daytime sleepiness and exhibit emotional/behavioral disturbances. • In the typically developing population, sleepiness is associated with emotional/behavioral disturbances, independently of sleep-disordered breathing. . What is New: • This study found evidence for a direct link between daytime sleepiness and emotional/behavioral disturbances, independent of sleep-related breathing difficulties, sleep adequacy, and body mass index. • Excessive daytime sleepiness may be a modifiable risk factor for emotional/behavioral disturbances in PWS.
Publisher: The Endocrine Society
Date: 05-1992
DOI: 10.1210/ENDO.130.5.1374015
Abstract: The somatogenic effects of recombinant ovine placental lactogen (oPL) were investigated in the GH-deficient dwarf rat and compared to those of identical doses of recombinant bovine GH (bGH) in three independent studies. Both oPL and bGH treatments resulted in an increase (P less than 0.05) in body weight gain compared to that in saline controls, with oPL treatment being more potent than bGH (P less than 0.05). In promoting linear growth, oPL was more potent (P less than 0.05) than bGH in some instances. The nitrogen content of dry carcass matter was increased with oPL treatment compared to saline (P less than 0.05), with a nonsignificant increase in bGH-treated animals. Carcass fat was similarly reduced by both oPL and bGH treatment (P less than 0.05) compared to saline. Serum insulin-like growth factor-I (IGF-I) concentrations were increased significantly (P less than 0.05) by both oPL and bGH treatments, with a significantly greater effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was evident with either treatment, suggesting that the increase in serum IGF-I is due to posttranscriptional mechanisms. The expression of IGF-binding protein-3 hepatic mRNA was increased (P less than 0.05) with bGH treatment compared to that after saline treatment, but was unaffected by oPL treatment, indicating regulation by GH at the transcriptional level. The binding of [125I]bGH to hepatic membrane preparations demonstrated no difference in specific binding compared to that in saline controls. However, [125I]oPL specific binding was greater in oPL-treated animals (P less than 0.05). Animals treated with bGH had reduced (P less than 0.05) hepatic GH receptor mRNA compared to saline controls, but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic agent in the dwarf rat, exerting greater somatogenic effects on some parameters than bGH. Our data suggest differences in receptor binding and effects on GH receptor and IGF-binding protein-3 expression with these two treatments, raising the possibility of actions through different pathways or differential effects at the GH receptor level.
Publisher: Oxford University Press (OUP)
Date: 04-2007
DOI: 10.1530/EJE-06-0700
Abstract: Objective : The aim of glucocorticoid replacement therapy in ACTH-deficient patients is to mimic the normal diurnal variation of cortisol. However, current hydrocortisone (HC) replacement results in prolonged episodes of hypocortisolaemia and supraphysiological peaks. Plasma cortisol profiles are an accurate yet labour-intensive method of assessing HC replacement. Salivary and bloodspot cortisol s ling methods are less invasive and may be useful tools for assessing glucocorticoid replacement, particularly in children. Therefore, we aimed to define normal salivary and bloodspot cortisol levels in children and their correlations with the gold standard (plasma cortisol). Design : Cross-sectional study in a paediatric teaching hospital. Methods : Plasma, saliva and bloodspot cortisol profiles were performed on 30 ACTH-deficient children and 22 healthy siblings. Results : In ACTH-deficient patients taking oral HC, the bloodspot–plasma correlation (ρ = 0.90) was stronger than the salivary–plasma correlation (ρ = 0.49). Using target ranges for salivary and bloodspot cortisol levels based on normal data from control subjects, the less invasive s ling methods had low rates of agreement with plasma cortisol target ranges (saliva 65% and bloodspot 75%). Using the plasma–bloodspot correlation regression equation to convert bloodspot to calculated plasma cortisol, there was a high concordance between calculated and actual measured plasma cortisol (88%). Conclusion : Bloodspot cortisol s ling is a feasible and accurate method for monitoring oral HC replacement in paediatric patients without necessitating hospital admission, but salivary s ling is not useful.
Publisher: Frontiers Media SA
Date: 12-01-2021
DOI: 10.3389/FPSYG.2020.582688
Abstract: 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) (χ 2 = 52.66 p & 0.001) and had a high rate of unresolved loss/trauma (χ 2 = 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 (χ 2 = 2.43 p = 0.30) and rates of unresolved loss and trauma (χ 2 = 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.
Publisher: American Diabetes Association
Date: 14-10-2020
DOI: 10.2337/DC20-1447
Abstract: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR 70–180 mg/dL) during the final 3 weeks. Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19] P & 0.0001). For HCL, HbA1c was lower (median [95% CI] difference −0.4% [−0.6, −0.2] −4 mmol/mol [−7, −2] P & 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9] P & 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.
Publisher: The Endocrine Society
Date: 03-2013
DOI: 10.1210/JC.2012-3224
Publisher: Springer Science and Business Media LLC
Date: 25-11-2014
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1155/2009/431527
Publisher: Wiley
Date: 15-08-2011
DOI: 10.1111/J.1464-5491.2011.03322.X
Abstract: This study investigated whether continuous subcutaneous insulin infusion is associated with sustained improvement in behaviour and metabolic control. Children with Type 1 diabetes mellitus (n = 27, 8-18 years old) who had been assessed previously prior to commencing continuous subcutaneous insulin infusion, and 6-8 weeks later, were re-evaluated 2 years after commencing insulin pump therapy. Behaviour was reassessed using the Behavioral Assessment System for Children-2nd edition (BASC-2) and current HbA(1c) levels were recorded. Two years after commencing continuous subcutaneous insulin infusion, parent-reported internalizing and externalizing symptoms were significantly lower than pre-insulin pump therapy commencement levels. Self reports of internalizing and externalizing problems did not differ significantly across the three assessment points. There was no significant difference between pre-insulin pump therapy HbA(1c) and HbA(1c) after 2 years on continuous subcutaneous insulin infusion, despite an initial improvement 6-8 weeks after commencing the therapy. Children with Type 1 diabetes mellitus showed sustained improvements in parent-reported behaviour, but not in self reports of behaviour or in metabolic control 2 years after commencement of continuous subcutaneous insulin infusion.
Publisher: Mary Ann Liebert Inc
Date: 2019
Abstract: 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. 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 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). 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.
Publisher: Bioscientifica
Date: 04-1994
Abstract: While the GH receptor (GHR) plays a key role during adult life, its role during fetal development is not well understood. Recent data suggest that GHRs are present in ovine fetal hepatic tissue at mid-gestation. However, the levels of GHR expression are markedly lower in fetal hepatic tissue in comparison with postnatal values. The present study investigates whether the neonatal induction of the hepatic GHR and plasma levels of IGF-I follow a pattern of strictly age-related development or whether birth-associated processes stimulate this increase. Stereotaxic electrolytic lesioning of the fetal paraventricular nuclei was employed to prolong gestation markedly. We compared the hepatic binding of ovine placental lactogen (oPL) and oGH and plasma levels of IGF-I in these post-mature fetuses with those in pre-term fetuses, pregnant mothers and lambs which were of the same conceptional age as the post-mature fetuses. While specific binding of both 125 I-labelled oGH and 125 I-labelled oPL to hepatic microsomal membranes was fully reversible in all groups, the specific binding of 125 I-labelled oGH was significantly ( P ·001) lower than specific binding of 125 I-labelled oPL in all groups of animals. There was no difference in specific I-labelled oGH or 125 I-labelled oPL binding in livers or plasma levels of IGF-I in post-mature fetuses in comparison with pre-term fetuses. In contrast, a major increase ( P ·001) in 125 I-labelled oGH and 125 I-labelled oPL binding and plasma IGF-I levels was observed in lambs. In pregnant females, specific 125 I-labelled oGH and 125 I-labelled oPL binding and plasma IGF-I levels were significantly ( P ·01) higher compared with the two fetal groups. A significant ( P ·001) correlation was observed between specific binding with 125 I-labelled oGH and 125 I-labelled oPL ( r =0·95, intercept=4·5, slope=2·36). Detailed competitive binding studies showed that the potency of unlabelled oPL in competing with 125 I-labelled oPL or 125 I-labelled oGH was consistently higher in comparison with unlabelled oGH. The differences in cross-reactivity of oPL and oGH at the distinct developmental stages were related to the differences in affinity between the two ligands and major developmental increases in capacity. The present study shows major parallel induction of oPL and oGH binding to hepatic microsomal membranes and plasma IGF-I concentrations after birth. The postnatal increase in the hepatic GHR is inhibited if delivery is prevented by stereotaxic destruction of the fetal paraventricular nuclei. Our observation that oGH and oPL binding is co-ordinately induced after birth in hepatic tissue supports the emerging evidence that the two ligands may bind to the same membrane receptor or to related protein(s). Journal of Endocrinology (1994) 141, 101–108
Publisher: Wiley
Date: 13-08-2012
DOI: 10.1111/J.1464-5491.2012.03720.X
Abstract: To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration. This was a clinic-based observational cohort study of 4379 people aged ≤ 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2 yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥ III. Coeliac disease was confirmed by biopsy in 185 of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 ± 4.0 vs. 8.4 ± 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6-8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. ≥ 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2-2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001). Coeliac disease is common in young people with Type 1 diabetes the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children.
Publisher: S. KARGER AG
Date: 2014
DOI: 10.1159/000356352
Publisher: Oxford University Press (OUP)
Date: 12-2015
DOI: 10.1530/EJE-15-0474
Abstract: Meta-analysis has shown a modest improvement in first-year growth response to recombinant human GH (r-hGH) for carriers of the exon 3-deleted GH receptor (GHRd3) polymorphism but with significant interstudy variability. The associations between GHRd3 and growth response to r-hGH over 3 years in relation to severity of GH deficiency (GHD) were investigated in patients from 14 countries. Treatment-naïve pre-pubertal children with GHD were enrolled from the PREDICT studies (NCT00256126 and NCT00699855), categorized by peak GH level (peak GH) during provocation test: ≤4 μg/l (severe GHD n =45) and to μg/l mild GHD n =49) and genotyped for the GHRd3 polymorphism (full length (fl/fl, fl/d3, d3/d3). Gene expression (GE) profiles were characterized at baseline. Changes in growth (height (cm) and SDS) over 3 years were measured. There was a dichotomous influence of GHRd3 polymorphism on response to r-hGH, dependent on peak GH level. GH peak level (higher vs lower) and GHRd3 (fl/fl vs d3 carriers) combined status was associated with height change over 3 years ( P .05). GHRd3 carriers with lower peak GH had lower growth than subjects with fl/fl (median difference after 3 years −3.3 cm −0.3 SDS). Conversely, GHRd3 carriers with higher peak GH had better growth (+2.7 cm +0.2 SDS). Similar patterns were observed for GH-dependent biomarkers. GE profiles were significantly different between the groups, indicating that the interaction between GH status and GHRd3 carriage can be identified at a transcriptomic level. This study demonstrates that responses to r-hGH depend on the interaction between GHD severity and GHRd3 carriage.
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1016/J.JPEDS.2004.06.066
Abstract: The clinical side effects of the potent new bisphosphonate zoledronic acid in children are unknown. In this study of 34 children with various bone disorders, the frequency of postinfusion flu-like illness, hypocalcemia, and hypophosphatemia was 85%, 74%, and 82%, respectively. No renal side effects were detected after up to 3 consecutive infusions.
Publisher: Springer Science and Business Media LLC
Date: 09-04-2013
DOI: 10.1038/TPJ.2013.14
Publisher: The Endocrine Society
Date: 05-1992
DOI: 10.1210/ENDO.130.5.1315246
Abstract: Red deer antler tips in the growing phase were removed 60 days after the recommencement of growth for autoradiographical studies and RRAs. Sections were incubated with radiolabeled GH or insulin-like growth factor-I (IGF-I), with or without excess competing unlabeled hormones, and were analyzed autoradiographically. There was negligible binding of [125I]GH in any histological zone of antler sections. [125I]IGF-I showed highest specific binding in the chondroblast zone to a receptor demonstrating binding characteristics of the type 1 IGF receptor. The lowest specific binding of [125I]IGF-I was to prechondroblasts. RRAs on antler microsomal membrane preparations RRAs on antler microsomal membrane preparations confirmed the absence of GH receptors and the presence of type 1 IGF receptors found by autoradiography. These findings suggest that IGF-I may act in an endocrine manner in antler growth through a receptor resembling the type 1 IGF receptor. The presence of type 1 receptors in the chondroblast zone implicates IGF-I involvement in cartilage formation through matrixogenesis. There is no support for IGF-I having a major role in mitosis in the antler.
Publisher: Wiley
Date: 14-10-2001
DOI: 10.1046/J.1440-1754.2001.00748.X
Abstract: To review the presentation, management and outcome of persistent hyperinsulinaemic hypoglycaemia of infancy seen at the Royal Alexandra Hospital for Children over a 10 year period. A retrospective review of 20 subjects was performed. As well as laboratory data, data were collected on clinical presentation, medical and surgical management and developmental outcome. Twenty subjects (11 male) were identified with presentation at a median age of 1.5 months (range 0-10 months), with 10 (50%) presenting in the first week of life. Only 20% of patients were large for gestational age. Diagnosis was made on the basis of high glucose requirements and inappropriately high insulin levels at the time of hypoglycaemia. Eight (40%) responded well to diazoxide treatment alone, seven (35%) received diazoxide in combination with other short-term medical therapy initially and five (25%) required pancreatectomy (repeat surgery in three). Those who required surgery had a higher mean birth weight. Infants presenting in the first week of life were less likely to respond to diazoxide. At the time of last review, eight (40%) of those treated medically had ceased all treatment. Two of the five cases requiring pancreatectomy now require insulin treatment. Neurodevelopmental assessment was normal in 11 (55%), mild delay was found in six (30%) and moderate or severe delay was found in three (15%). Persistent hyperinsulinaemic hypoglycaemia of infancy remains a major diagnostic and management challenge. Early suspicion and recognition is critical with definitive investigation and medical therapy to avoid hypoglycaemia, with pancreatectomy in medically unresponsive cases. Normal neurodevelopmental outcome was found in only 55% of cases.
Publisher: Wiley
Date: 16-08-2022
DOI: 10.1111/JPC.15691
Abstract: In children with Prader‐Willi syndrome (PWS), growth hormone (GH) improves height and body composition however, may be associated with worsening sleep‐disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow‐up with polysomnography is still advised in most clinical guidelines. This retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed‐rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals. We included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1–13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0–32.9) 35% had an obstructive AHI above 1.0/h. Follow‐up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly ( P = 0.13), but 12 children (13%, CI 95% 7–21%) developed moderate/severe OSA, with clinical management implications. Our findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.
Publisher: Oxford University Press (OUP)
Date: 09-2013
DOI: 10.1530/EJE-13-0069
Abstract: In idual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for in idualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). A prospective, multicenter, international, open-label pharmacogenomic study. The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable ided into quartiles. Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For ex le, in GHD, GRB10 was associated with high response (≥ Q 3 P =0.0012), while SOS2 was associated with low response (≤ Q 1 P =0.006), while in TS, LHX4 was associated with high response ( P =0.0003) and PTPN1 with low response ( P =0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD ( AKT1 ) and for two in TS ( KRAS and MYOD1 ). Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in in idualized management of childhood growth disorders.
Publisher: Springer Science and Business Media LLC
Date: 06-11-2009
DOI: 10.1007/S00125-008-1197-3
Abstract: Anecdotally, parents and teachers of children with type 1 diabetes mellitus report improvements in behaviour and learning following the commencement of continuous subcutaneous insulin infusion (CSII). This study aimed to investigate changes in cognition, mood and behaviour following commencement of CSII in children with type 1 diabetes. Children (n = 32) with type 1 diabetes aged 6-16 years and starting CSII at two Australian centres underwent behavioural, cognitive and glycaemic assessments prior to the commencement of CSII and 6-8 weeks after its start. A comprehensive cognitive test battery was administered, comprising measures of intelligence, attention, processing speed and executive skills. Behaviour and mood were assessed using the Behaviour Assessment System for Children--Second Edition. Continuous glucose monitoring was performed over a 72 h period and HbA(1c) was measured at both time-points. After commencement of CSII, there were significant improvements in HbA(1c), a reduction in hyperglycaemia and blood glucose variation and an increase in normoglycaemia. Significant improvements were observed in perceptual reasoning, selective attention, ided attention, cognitive flexibility and working memory. Fewer mood-related symptoms were reported (parent, teacher and self-report) and fewer behavioural problems (parent reports) In this uncontrolled pilot study, children with type 1 diabetes demonstrated significant improvements in measures of metabolic control, mood and behaviour and in some complex cognitive skills after commencing CSII therapy.
Publisher: BMJ
Date: 14-06-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2002
DOI: 10.1097/00019605-200210000-00005
Abstract: We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1194/JLR.S087163
Publisher: Springer Science and Business Media LLC
Date: 24-03-2017
DOI: 10.1038/SREP45286
Abstract: The gluten free diet (GFD) has a high glycemic index and low-fiber content, which potentially influences glycemic excursions in type 1 diabetes (T1D) and celiac disease (CD). Participants in this case-control study of youth with T1D+CD (n = 10) and T1D only (n = 7) wore blinded continuous glucose monitoring systems for six days. Blood glucose levels (BGLs) were compared between groups for each meal, including pre-meal, peak, 2-hour postprandial and time-to-peak. Participants consumed a test-breakfast of GF cereal and milk for three days and kept weighed food diaries nutrient intake was analyzed and compared to national recommendations. Youth with T1D+CD had shorter time-to-peak BGL (77 vs 89 mins, P = 0.03), higher peak (9.3 vs 7.3 mmol/L, P = 0.001) and higher postprandial BGLs than T1D (8.4 vs 7.0 mmol/L, P = 0.01), despite similar pre-meal BGLs (9.2 vs 8.6 mmol/L, P = 0.28). Regarding test breakfast, greater pre and post-meal BGL difference correlated with longer CD duration (R = 0.53, P = 0.01). Total energy and macronutrient intake didn’t differ between groups however the majority of participants collectively had inadequate intake of calcium (76%), folate (71%) and fiber (53%), with excessive saturated fat (12%) and sodium ( ,000 mg/day). The GFD is associated with greater glycemic excursions and inadequate nutritional intake in youth with T1D+CD. Clinical management should address both glycemic variability and dietary quality.
Publisher: Informa UK Limited
Date: 19-06-2019
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
Publisher: Mary Ann Liebert Inc
Date: 09-2016
Abstract: 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. 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 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. SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.
Publisher: Oxford University Press (OUP)
Date: 02-1992
Abstract: We evaluated the interrelationship between, and regulation of, the hepatic growth hormone receptor and serum GH binding protein (GH BP) in pigs treated with recombinant porcine growth hormone (rpGH). Infant and pubertal male pigs (N = 5 per group) received either rpGH 0.15 mg/kg daily or diluent intramuscularly for 12 days. Somatic growth, serum IGF-I and GH BP and [ 125 I]bovine GH (bGH) binding to MgCl 2 -treated hepatic membrane homogenates were examined. Marked age-related increases were seen in serum GH BP (p .001) and [ 125 I]bGH binding to hepatic membranes (p .001). GH BP was increased in rpGH treated animals (p = 0.03), from 13.8±1.2 (mean±1 x sem ) (controls) to 17.8±2.0% in infants, and from 35.2±2.6 (controls) to 41.8±3.4% in pubertal animals. [ 125 I]bGH binding to hepatic membranes was also increased by rpGH treatment (p .05), from 7.0±1.6 (controls) to 15.4±3.6% in infants and from 53.7±7.1 (controls) to 65.1±11.8% in pubertal animals. No significant interaction between age and treatment was seen. Overall, serum GH BP correlated significantly with [ 125 I]bGH membrane capacity (r=0.82, p .001), with a correlation of r= 0.83 in the infant animals but no significant correlation in the pubertal animals considered alone (r=0.13). Serum IGF-I correlated significantly with serum GH BP (r=0.93, p .001) and [ 125 ]bGH membrane binding capacity (r = 0.91, p 0.001). These observations suggest that serum GH BP levels reflect major changes of hepatic GH receptor status. In addition, the present study demonstrates that the hepatic GH receptor can be induced by GH in the infant pig, despite a developmentally low GH receptor population at this age, suggesting potential efficacy of GH at earlier ages than generally considered.
Publisher: Mary Ann Liebert Inc
Date: 09-2014
Abstract: 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. Phone calls to our 24-h diabetes support service were screened for CSII-associated AEs. Phone interviews were conducted with the parent atient, 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. 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. 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.
Publisher: MDPI AG
Date: 07-02-2023
Abstract: 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 (in idual 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 s les of children and adolescents seeking a GD diagnosis and gender-affirming medical care, outcome pathways follow a erse range of possibilities.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.CLNU.2012.02.012
Abstract: There is significant interest in the utility of flexible meal plans for in iduals with type 1 diabetes. However, there is a paucity of data examining this approach in adolescents. The aim of this study was to assess glycemic control, weight status and quality of life over 12 months in adolescents with type 1 diabetes, who were commenced on a flexible meal plan using an insulin to carbohydrate ratio. 38 adolescents with type 1 diabetes were recruited and 28 completed the study. Glyceamic control, weight status and quality of life were measured using haemoglobin A1c, BMI and the Diabetes Quality of Life -Youth questionnaire. Nine months after the adolescents were transitioned to a flexible meal and insulin plan, mean BMI SDS decreased (by 0.15 ± 0.20 P < 0.001) and haemoglobin A1c increased (by 0.7 ± 0.83% P = 0.001). Adolescents reported no change in the impact or concerns about diabetes. However, mean life satisfaction scores increased (5.5 ± 9.5 P = 0.008). On a flexible meal and insulin plan glycemic control deteriorated although weight status and life satisfaction, two outcomes which may be important to the adolescents, improved. A flexible meal and insulin plan warrants further investigation as a management option.
Publisher: SAGE Publications
Date: 22-06-2016
Abstract: Managing type 1 diabetes mellitus is an ongoing and challenging process we investigated children’s experience of different treatment regimens. Interviews with 17 children (7–15 years) at two time points were analysed using the grounded theory approach. Illness phase and treatment regimen shaped how bodily cues were interpreted. Insulin pump therapy allowed children to listen to and trust their bodily cues rather than override. Shame was a barrier to support engagement. Different internalised and externalised views of type 1 diabetes mellitus emerged. Overall, children were insightful experts of their own experiences. Recommendations for psychological interventions would benefit from empirical testing.
Publisher: American Diabetes Association
Date: 25-05-2017
DOI: 10.2337/DC16-2508
Abstract: Celiac disease (CD) has a recognized association with type 1 diabetes. We examined international differences in CD prevalence and clinical characteristics of youth with coexisting type 1 diabetes and CD versus type 1 diabetes only. Data sources were as follows: the Prospective Diabetes Follow-up Registry (DPV) (Germany/Austria) the T1D Exchange Clinic Network (T1DX) (U.S.) the National Paediatric Diabetes Audit (NPDA) (U.K. [England/Wales]) and the Australasian Diabetes Data Network (ADDN) (Australia). The analysis included 52,721 youths & years of age with a clinic visit between April 2013 and March 2014. Multivariable linear and logistic regression models were constructed to analyze the relationship between outcomes (HbA1c, height SD score [SDS], overweight/obesity) and type 1 diabetes/CD versus type 1 diabetes, adjusting for sex, age, and diabetes duration. Biopsy-confirmed CD was present in 1,835 youths (3.5%) and was diagnosed at a median age of 8.1 years (interquartile range 5.3–11.2 years). Diabetes duration at CD diagnosis was & year in 37% of youths, & –2 years in 18% of youths, & –5 years in 23% of youths, and & years in 17% of youths. CD prevalence ranged from 1.9% in the T1DX to 7.7% in the ADDN and was higher in girls than boys (4.3% vs. 2.7%, P & 0.001). Children with coexisting CD were younger at diabetes diagnosis compared with those with type 1 diabetes only (5.4 vs. 7.0 years of age, P & 0.001) and fewer were nonwhite (15 vs. 18%, P & 0.001). Height SDS was lower in those with CD (0.36 vs. 0.48, adjusted P & 0.001) and fewer were overweight/obese (34 vs. 37%, adjusted P & 0.001), whereas mean HbA1c values were comparable: 8.3 ± 1.5% (67 ± 17 mmol/mol) versus 8.4 ± 1.6% (68 ± 17 mmol/mol). CD is a common comorbidity in youth with type 1 diabetes. Differences in CD prevalence may reflect international variation in screening and diagnostic practices, and/or CD risk. Although glycemic control was not different, the lower height SDS supports close monitoring of growth and nutrition in this population.
Publisher: The Endocrine Society
Date: 09-1994
DOI: 10.1210/ENDO.135.3.8070387
Abstract: The GH receptor (GHR) plays a key role in postnatal growth regulation. Although plasma concentrations of GH are high during fetal life, its role during fetal development is not well understood. Recent data suggest that GHR are present in fetal hepatic tissue as early as 51 days gestation. However, the levels of GHR expression are markedly lower in fetal hepatic tissue compared to postnatal values, and there are conflicting data suggesting that ovine placental lactogen (oPL) and oGH share a common receptor. Given the uncertainty about whether oPL acts via the oGHR or a distinct receptor, we performed ligand binding and affinity cross-linking studies on hepatic microsomal membranes from adult castrated male, pregnant female, and fetal sheep. Ligand binding assays at a constant concentration of membranes showed that [125I]oPL yielded consistently higher (P < 0.001) specific binding (59.5 +/- 6.4%, 30.5 +/- 5.7%, and 7.6 +/- 2.4% for castrated male, pregnant female, and fetal sheep, respectively) compared to [125I]oGH (17.8 +/- 4.7%, 5.0 +/- 1.6%, and 1.2 +/- 0.4% for castrated male, pregnant female, and fetal sheep, respectively). Cross-reactivity studies showed that unlabeled oPL was consistently more potent than unlabeled oGH in displacing either of the labeled ligands. The dissociation constant (Kd) for oPL binding ranged from 0.16-0.40 nM and was not changed by solubilization with Triton X-100. Equilibrium binding analysis for oGH showed lower affinity for hepatic microsomal membranes (Kd, 1.7-3.2 nM) in each of the three groups of animals. Affinity cross-linking of microsomal membranes from castrated male and pregnant female sheep liver showed four major cross-linked complexes with both [125I]oPL and [125I]oGH, with mol wt of 150, 97, 75, and 60 kilodaltons. All four bands were identified with both ligands. Unlabeled oPL showed markedly higher potency than unlabeled oGH in reducing the signal of the [125I]oPL cross-linked complexes, whereas unlabeled oGH and oPL showed comparable potencies in reducing the signal of the [125I]oGH complexes. Immunoprecipitation of detergent-solubilized hepatic microsomal membranes from pregnant and fetal sheep using a panel of monoclonal antibodies raised against the extracellular region of the rabbit GHR showed potent immunological recognition of the [125I]oPL-receptor complexes. We suggest that oGH and oPL bind to a common or a related receptor protein(s). It is possible that differences in receptor dimerization or association with other membrane proteins are the basis of the differences in affinity and biological actions of the two hormones.
Publisher: The Endocrine Society
Date: 06-2013
DOI: 10.1210/JC.2012-3888
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
DOI: 10.1097/MED.0B013E32832B20A8
Abstract: Delayed puberty in men is a commonly presenting problem to paediatricians and an understanding of the available evidence on cause, treatments and outcomes is important to guide practice. Understanding of the regulation of the onset of puberty is gradually unfolding, although the genetic factors that dictate the timing of puberty in in iduals and families remain poorly elucidated. Mutations and polymorphisms in candidate genes are being actively studied and it is likely that there is significant overlap between traditional diagnostic categories. Also, environmental endocrine disruptors may interact with the genetic regulation of puberty. Delayed puberty may not always be a benign condition, with increased risks of failing to achieve target height, adverse psychological and educational consequences, delayed sexual and psychosocial integration into society and effects on skeletal proportions and bone mass reported. Appropriate evaluation and follow-up is needed to guide clinical practice, particularly to distinguish constitutional delay in growth and puberty from that associated with other medical disease or permanent disorders. In milder cases of delayed puberty, treatment is often not required however, considerable evidence exists for the efficacy and safety of short courses of low-dose testosterone therapy for appropriately selected in iduals. This treatment is associated with high levels of patient satisfaction. There is not yet sufficient evidence for the routine use of other therapies (e.g. growth hormone, aromatase inhibitors) for constitutional delay in growth and puberty and better characterization of cause may lead to more targeted in idual therapy.
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.1007/S00431-003-1328-2
Abstract: We report on transient hyperinsulinism (HI), presenting as severe congenital HI, in two neonates born without intrauterine growth restriction, maternal diabetes, perinatal asphyxia or Rhesus latelet isoimmunisation. The neonates developed early (<6 h of life), symptomatic, non-ketotic hypoglycaemia (0-0.66 mmol/l), associated with elevated insulin levels (40-200 mU/l), and required high glucose infusion rates (22-24 mg/kg per min) to maintain normoglycaemia. However, both babies were diazoxide-sensitive and did not require glucose infusions beyond 2 weeks of life. Neither neonate had elevated serum ammonia levels or evidence of a metabolic disorder. Transient hyperinsulinism can occur in newborns delivered uneventfully without significant perinatal complications. The unusual sensitivity to medical treatment in these cases of neonatal-onset hyperinsulinaemic hypoglycaemia underscores the importance of careful medical management of severe congenital hyperinsulinism. Careful consideration of the indication and if necessary, timing and extent of pancreatectomy is required, while maintaining euglycaemia to protect the developing brain.
Publisher: Wiley
Date: 07-2006
DOI: 10.1111/J.1440-1754.2006.00889.X
Abstract: Abstract: The reporting of the results of the Diabetes Control and Complications Trial in 1993 has led to a major reappraisal of management practices and outcomes in type 1 diabetes in children and adolescents. A considerable body of outcome data has been generated from Australia in this post‐Diabetes Control and Complications Trial era relating to incidence, metabolic control, growth, hypoglycaemia, microvascular and macrovascular complications, cognition, behaviour and quality of life. These data are important in planning future management strategies and resource allocation and as a basis for future research.
Publisher: Walter de Gruyter GmbH
Date: 1997
DOI: 10.1515/JPEM.1997.10.1.27
Abstract: In Turner's syndrome there is marked heterogeneity of growth response to growth hormone (GH) therapy. The study aim was to identify pretreatment factors that influence response to GH therapy. The 70 subjects recruited were prepubertal, had not received sex steroids and had received 28 units/m2/week of GH for > or = 1 year. Pretreatment variables associated with the greatest improvement in height SDS (r2 = 0.58) were weight for length index (p = 0.0001), target height (p = 0.004), bone age delay (p = 0.008) and age (p = 0.04). In conclusion, during two years of GH therapy the best growth response occurred in girls who were younger, heavier, had a delayed bone age and tall parents. Height SDS as a continuous variable is the most effective measure of growth when considering pretreatment factors that may influence response to GH therapy.
Publisher: BMJ
Date: 08-2018
DOI: 10.1136/BMJOPEN-2017-020275
Abstract: Automated insulin delivery (also known as closed loop, or artificial pancreas) has shown potential to improve glycaemic control and quality of life in people with type 1 diabetes (T1D). Automated insulin delivery devices incorporate an insulin pump with continuous glucose monitoring(CGM) and an algorithm, and adjust insulin in real time. This study aims to establish the safety and efficacy of a hybrid closed-loop (HCL) system in a long-term outpatient trial in people with T1D aged 12 – years of age, and compare outcomes with standard therapy for T1D as used in the contemporary community. This is an open-label, multicentre, 6-month, randomised controlled home trial to test the MiniMed Medtronic 670G system (HCL) in people with T1D aged 12 – years, and compare it to standard care (multiple daily injections or continuous subcutaneous insulin infusion (CSII), with or without CGM). Following a run-in period including diabetes and carbohydrate counting education, dosage optimisation and baseline glucose control data collection, participants are randomised to either HCL or to continue on their current treatment regimen. The primary aim of the study is to compare the proportion of time spent in target sensor glucose range (3.9–10.0 mmol/L) on HCL versus standard therapy. Secondary aims include a range of glucose control parameters, psychosocial measures, health economic measures, biomarker status, user/technology interactions and healthcare professional expectations. Analysis will be intention to treat. A study in adults with an aligned design is being conducted in parallel to this trial. Ethics committee permissions were gained from respective institutional review boards. The findings of the study will provide high-quality evidence on the role of HCL in clinical practice.
Publisher: Wiley
Date: 07-03-2011
DOI: 10.1111/J.1365-2265.2011.03937.X
Abstract: 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. Short stature is the most common clinical manifestation of TS. GH treatment improves growth. Response was measured for each year of treatment. Stepwise multiple regression analyses were used to identify factors that significantly influenced response. 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. 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. 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. 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.
Publisher: Bioscientifica
Date: 07-1992
Abstract: Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P .01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I 10μg 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1μg/g body weight per day), bovine GH (bGH 0.6μg/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P 0.01) maternal constraint and altered (P .01) the relationship between placental and fetal weight. When high or low IGF-I line mice embryos were transplanted into a normal line of mice, the expected negative relationship (P .05) between mean fetal weight and litter size was maintained. However the embryos of the high line were heavier (P .05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth. Thus both endogenous and exogenous elevations in maternal IGF-I indirectly promote fetal growth either by altering nutrient delivery to the placenta or by affecting placental function.
Publisher: AMPCo
Date: 09-2002
DOI: 10.5694/J.1326-5377.2002.TB04754.X
Abstract: To audit glycaemic control and incidence of severe hypoglycaemia in children and adolescents with type 1 diabetes in New South Wales (NSW) and the Australian Capital Territory (ACT). A multicentre, population-based, cross-sectional study from 1 September to 31 December, 1999. 1190 children and adolescents aged 1.2-15.8 years with type 1 diabetes, identified from three hospital-based paediatric diabetes units, four private city-based paediatric practices and 18 regional outreach clinics in NSW and the ACT. HbA(1c) level and incidence of severe hypoglycaemia (defined by unconsciousness or seizures). The response rate was 67% (1190 of a target group of 1765). The median HbA(1c) level was 8.2% (interquartile range, 7.6%-9.1%). Significant predictors of HbA1c level in a multiple regression model were duration (b = 0.05 95% CI, 0.02-0.07) and insulin dose/kg (b = 0.46 95% CI, 0.27-0.66). At least one episode of severe hypoglycaemia in the previous three months was reported in 6.7%, and the rate of severe hypoglycaemia was 36/100 patient-years. Significant predictors of hypoglycaemia in a Poisson regression model were younger age (P = 0.03), male sex (P = 0.04), longer diabetes duration (P = 0.02), and > 3 daily insulin injections (P = 0.02), but not HbA(1c) level. Children with diabetes had higher BMI standard deviation scores compared with population standards, and those in the highest quartile of BMI standard deviation score were younger, had shorter diabetes duration and had higher HbA(1c) level. Many children and adolescents with type 1 diabetes have suboptimal glycaemic control, placing them at high risk of developing microvascular complications. Those with longer diabetes duration are at increased risk of suboptimal glycaemic control and severe hypoglycaemia and should be targeted for interventional strategies.
Publisher: Mary Ann Liebert Inc
Date: 07-2016
Abstract: 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. 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. 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. SAPT with PLGM reduced the requirement for hypoglycemia treatment following insulin-induced hypoglycemia in an in-clinic setting.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
Publisher: Hindawi Limited
Date: 12-2004
Publisher: Mary Ann Liebert Inc
Date: 02-2016
Publisher: American Diabetes Association
Date: 10-2007
DOI: 10.2337/DC07-0603
Publisher: Elsevier BV
Date: 05-1994
DOI: 10.1016/0303-7207(94)90249-6
Abstract: The rat IGF-I gene consists of six exons, with exons 3 and 4 forming a 'core' mature IGF-I coding region to which alternate 5' and 3' regions are spliced. Transcription occurs from four dispersed start sites (ss) approximately 382 (ss 1), approximately 343 (ss 2), approximately 245 (ss 3) and approximately 30-40 (ss 4) basepairs (bp) from the 3' end of exon 1, and from a region 50-70 bp from the 3' end of exon 2. The expression of ss mRNAs displays tissue-specific and ontogenic regulation. Alternate splicing of exon 5 produces E-peptide coding domain variants (Ea and Eb mRNAs), with the Eb form found predominantly in the liver. The regulation of IGF-I mRNA expression by GH and IGF-I in the GH-deficient dwarf (dw/dw) rat was investigated using antisense RNA probes in a solution hybridization RNase protection assay to detect leader exon and E domain variant mRNAs. GH treatment of dw/dw and normal Lewis rats increased the expression of all liver leader exon ss and E domain variants coordinately (1.6-1.9-fold increase, p < 0.01), although the increase observed in Eb transcripts was significantly higher in the dw/dw compared to the normal rat (p < 0.05). In kidney, GH treatment significantly increased exon 1 ss 3 and ss 4 transcripts by approximately 40% (p < 0.05). The expression of the other start sites was not affected by GH, suggesting that transcription factors may regulate start site usage independently. GH treatment was associated with a significant increase in IGF-I mRNA expression in skeletal muscle (p < 0.05) but not cardiac muscle or spleen. IGF-I treatment was associated with minor (approximately 20%) but significant (p < 0.05) reductions in IGF-I mRNA expression in the liver and kidney of dw/dw rats, suggesting that IGF-I can suppress IGF-I mRNA expression. IGF-I treatment did not affect IGF-I mRNA expression in cardiac and skeletal muscle of dw/dw rats. IGF-I receptor mRNA was detected in extrahepatic tissues only, and was not affected by either GH or IGF-I treatment. In summary, start site-specific regulation by GH was observed in kidney. GH increased IGF-I mRNA expression in muscle, kidney and liver, but had no effect in heart or spleen in the dw/dw rat. Our data suggest that systemic IGF-I can feedback on hepatic and renal IGF-I mRNA expression in the GH-deficient state.
Publisher: SAGE Publications
Date: 14-01-2018
Abstract: Continuous glucose monitoring can improve glycemic outcomes in in iduals with type 1 diabetes. However, the constant exposure to real-time glucose levels can sometimes lead the in idual to make some risky choices to address the glycemic excursions. Hence, the purpose of this study was to explore the aberrant management behaviors of youth with type 1 diabetes on sensor-augmented pump therapy (SAPT). Participants in a clinical trial using SAPT on Medtronic MiniMed™ 640G pump who experienced deteriorating glycemic control or unexplained hypoglycemia were identified by the health care professional. The pump and/or sensor data uploaded to CareLink™ Therapy Management Software were reviewed in these participants. Uncharacteristic management behaviors were identified in five adolescent males. Continuous exposure to high glucose levels resulted in obsessive behaviors displaying a perfectionistic attitude in two participants. Multiple boluses were delivered frequently as uneaten carbohydrates in participant 1 while participant 2 resorted to delivery of extra insulin by cannula fills. In contrast, participant 3 chose to remain hyperglycemic to avoid weight gain while participant 4 trusted the system and used sensor glucose readings for calibrations, with resultant deterioration in glycemic control in both participants. On the other hand, participant 5, due to mistrust in the pump suspend function, consumed carbohydrates with downward glucose trends with rebound hyperglycemia. Constant exposure to real-time data can lead to unsafe management responses in adolescents with the behavior influenced by trust or mistrust in the system. Adolescents should be empowered with problem-solving strategies for safe management.
Publisher: American Diabetes Association
Date: 09-2001
Publisher: Mary Ann Liebert Inc
Date: 04-2013
Abstract: 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. 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. 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). 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.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.GHIR.2017.03.001
Abstract: Evaluate benefit and risk of low dose growth hormone treatment (GHT, 4.5mg/m Prospective longitudinal clinical intervention. We evaluated 31 infants (aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for height, weight and BMI using the World Health Organization standard deviation scores (SDS At commencement of GHT infants had a lower BMI SDS Initiation of GHT in infants with 4.5mg/m
Publisher: American Diabetes Association
Date: 04-06-2019
DOI: 10.2337/DC18-2376
Abstract: This study compared bone health in youth with type 1 diabetes and celiac disease (CD) versus type 1 diabetes alone. This was a case-control study of 42 youth with coexisting type 1 diabetes and CD and 40 with type 1 diabetes matched for age, sex, diabetes duration, and HbA1c. Bone mineral density (BMD), bone mineral content (BMC), and BMC-to-lean tissue mass (LTM) ratio were measured using DXA and reported as z-scores for height. Total, trabecular, and cortical bone and muscle parameters were measured using peripheral quantitative computed tomography (pQCT) and reported as z-scores for age. Mean age at assessment was 14.3 ± 3.1 years diabetes duration, 8.0 ± 3.5 years HbA1c, 8.2 ± 1.5% (66 ± 5 mmol/mol) and 25-hydroxy vitamin D, 71 ± 21 nmol/L. Comparing youth with coexisting CD versus type 1 diabetes alone, DXA showed lower BMC-to-LTM ratio (0.37 ± 1.12 vs. 0.73 ± 2.23, P = 0.007) but no difference in total BMD. Youth with coexisting CD also had lower BMC-to-LTM ratio versus the general population (P = 0.04). Radial pQCT showed lower total BMC (−0.92 ± 1.40 vs. −0.26 ± 1.23, P = 0.03) despite similar bone and muscle cross-sectional area. In multivariable linear regression, lower BMC was associated with higher insulin dose (P = 0.03) but not HbA1c. Youth with both type 1 diabetes and CD have lower BMC relative to LTM and lower BMC, indicating abnormal trabecular and cortical bone development despite similar bone and muscle size. These findings suggest that the two conditions confer a lower bone turnover state. We recommend further examination of bone health in this population future research should examine early interventions to improve bone health.
Publisher: Wiley
Date: 23-02-2004
DOI: 10.1111/J.1440-1754.2004.00307.X
Abstract: Continuous, automated and non-invasive blood glucose monitoring systems have long been a goal to assist management of diabetes mellitus. The first continuous, albeit invasive, device available in Australia is the Medtronic MiniMed Continuous Glucose Monitoring System (CGMS), which is available for physician-supervised use to give a continuous blood glucose profile (5-minutely readings, viewable only after download by the physician) for periods of 72 h. With the availability of this technology, there is a need to assess the accuracy, reproducibility and ability to detect significant clinical events (particularly hypoglycaemia) and blood glucose patterns. The question of whether this technique allows long-term improvement of metabolic control also arises. We present four case studies to illustrate the use of CGMS in clinical practice and have reviewed the rapidly emerging literature. We conclude that CGMS is a useful clinical tool in the management of diabetes mellitus, provided that it is appropriately applied and the limitations are understood.
Publisher: Elsevier BV
Date: 12-1992
DOI: 10.1016/S0022-3476(05)80342-7
Abstract: To assess the role of growth hormone in fetal and infant growth, we analyzed the pretreatment data on 52 patients with a diagnosis of congenital growth hormone deficiency before 2 years of age, obtained from the Kabi Pharmacia International Growth Study. These infants had reduced birth-length standard deviation scores, an excess of birth weight relative to length, and progressive growth failure. We conclude that congenital growth hormone deficiency may cause impaired growth in utero and early infancy, and that growth hormone plays an important role in perinatal and infantile growth.
Publisher: BMJ
Date: 08-1998
DOI: 10.1136/THX.53.8.656
Abstract: Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function. The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two ided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences. There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03) p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods. FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.
Publisher: Elsevier BV
Date: 03-1993
Publisher: Oxford University Press (OUP)
Date: 07-1993
Abstract: This study was designed to assess the effects of treatment with insulin-like growth factor-I (IGF-I) on cardiac function and structure in rats with an established cardiomyopathy. Adult male Wistar rats were injected with doxorubicin (2 mg.kg-1 subcutaneously) weekly for 12 weeks and either rhIGF-I (0.8 mg.kg-1.day-1 n = 16, D-I group) or saline (n = 25, D-S group) subcutaneously via an osmotic pump from weeks 9 to 12. A non-doxorubicin injected control group was also studied. After 12 weeks survivors were anaesthetised and cardiac output determined with radiolabelled microspheres. At postmortem pleural effusion and ascitic volumes were measured and the heart was removed for histological examination by light and transmission electron microscopy. Doxorubicin treated animals showed less mean weight gain from week 2 than the untreated control group. Animals treated with IGF-I from week 9 showed a significant (p < 0.05) but non-sustained increase in weight. Survival to 12 weeks was 56% in the D-I group and 44% in the D-S group (p = 0.2). Evidence of cardiac failure was seen in the D-I and the D-S groups, but there was a tendency (p = 0.06) for less ascites in the D-I group (21 (SEM 8) ml) than in the D-S group (46 (10) ml). Cardiac output was significantly higher in the D-I than in the D-S group (132 (7.2) v 91.4 (6.4) ml.min-1, p < 0.01), as was stroke volume (0.323 (0.03) v 0.226 (0.02) ml, p < 0.01). There was focal cardiac damage in both D-I and D-S animals. Scattered groups of myocytes showed prominent vacuolation of the nuclear envelope, sarcoplasmic reticulum, and t tubular system, mild to severe mitochondrial swelling, and loss of orientation and definition of myofibrils. No clear morphological differences were evident between the two groups. Administration of IGF-I may improve the function of damaged myocardium, although the mechanisms are unclear. Further studies with earlier coadministration of IGF-I, quantitative histological analysis, and with other models of cardiac injury are indicated.
Publisher: Wiley
Date: 19-06-2013
DOI: 10.1111/JPC.12294
Abstract: The Australian Prader-Willi Syndrome (PWS) database was established to monitor the efficacy and safety of growth hormone (GH) treatment in PWS. This study aims to compare response to GH based on eligibility criteria. Comparative study: 72 children received GH on the basis of short stature or evidence of GH deficiency (pre-2009: PWS-SS) and 94 on a genetic diagnosis (post-2009: PWS-Dx). We report on mandatory patient data for GH prescription: median and standard deviation score (SDS) for height and body mass index (BMI), waist/height ratio, bone age/chronological age ratio and adverse events. Comparisons were made using non-parametric tests. At baseline, the PWS-SS cohort was shorter (height SDS: -2.6 vs. -1.1, P < 0.001), had a lower BMI (0.6 vs. 1.5 SDS, P < 0.05) and greater bone age delay (bone age/chronological age: 0.7 vs. 0.9, P < 0.05) than the PWS-Dx cohort. PWS-SS parents were shorter (mid-parental height SDS: -0.13 vs. 0.28, P < 0.005). Mean change in height over 2 years was 0.9 SDS and in BMI using PWS reference standards -0.3 SDSPWS (n = 106) (year 2, height SDS: PWS-SS = -1.7, PWS-Dx = 0.1 BMI SDSPWS : PWS-SS = -1.0, PWS-Dx = -0.6). The waist/height ratio reduced (PWS-Dx: 0.60 vs. 0.56, P < 0.05) and bone age delay was unchanged over this period. No serious adverse events were reported. The PWS-SS cohort represents a subgroup of the wider PWS-Dx population however both cohorts improved height SDS with normalisation of height in the PWS-Dx cohort and lowering of BMI relative to PWS standards supporting the efficacy of treatment under the current Australian GH programme.
No related grants have been discovered for Geoffrey Ambler.