[show abstract][hide abstract] ABSTRACT: Management of Type 1 diabetes is associated with substantial personal and psychological demands which are often exacerbated during adolescence thus placing young people at significant risk for mental health problems. Supportive parenting can mitigate these risks, however the challenges and stresses associated with parenting a child with a chronic illness can interfere with a parent's capacity to parent effectively. Therefore, interventions that provide support for both the adolescent and their parents are needed to prevent mental health problems in adolescents; to build and maintain positive parent-adolescent relationships; and to empower young people to better self-manage their Type 1 diabetes. This paper presents the research protocol for a study evaluating the efficacy of the Nothing Ventured Nothing Gained online adolescent and parenting intervention. The intervention aims to improve the mental health outcomes of adolescents with Type 1 diabetes.Method/design: A randomized controlled trial using repeated measures with two arms (intervention and wait-list control) will be used to evaluate the efficacy and acceptability of the online intervention. Approximately 120 adolescents with Type 1 diabetes, aged 13-18 years and one of their parents/guardians will be recruited from pediatric diabetes clinics across Victoria, Australia. Participants will be randomized to receive the intervention immediately or to wait 6 months before accessing the intervention. Adolescent, parent and family outcomes will be assessed via self-report questionnaires at three time points (baseline, 6 weeks and 6 months). The primary outcome is improved adolescent mental health (depression and anxiety). Secondary outcomes include adolescent behavioral (diabetes self-management and risk taking behavior), psychosocial (diabetes relevant quality of life, parent reported child well-being, self-efficacy, resilience, and perceived illness benefits and burdens); metabolic (HbA1c) outcomes; parent psychosocial outcomes (negative affect and fatigue, self-efficacy, and parent experience of child illness); and family outcomes (parent and adolescent reported parent-adolescent communication, responsibility for diabetes care, diabetes related conflict). Process variables including recruitment, retention, intervention completion and intervention satisfaction will also be assessed.
The results of this study will provide valuable information about the efficacy, acceptability and therefore the viability of delivering online interventions to families affected by chronic illnesses such as Type 1 diabetes.Trial registration: Australian New Zealand clinical trials registry (ANZCTR); ACTRN12610000170022.
BMC Public Health 12/2013; 13(1):1185. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Adolescents with Type 1 diabetes (T1D) show less effective metabolic control than other age groups, partly because of biological changes beyond their control and partly because in this period of developmental transition, psychosocial factors can militate against young people upholding their lifestyle and medical regimens. Parents have an important role to play in supporting adolescents to self-manage their disease, but resultant family tensions can be high. In this study, we aimed to assess family functioning and adolescent behaviour/ adjustment and examine the relationships between these parent-reported variables and adolescent metabolic control (HbA1c), self-reported health and diabetes self-care. METHOD: A sample of 76 parents of Australian adolescents with T1D completed the Child Health Questionnaire --Parent form. Their adolescent child with T1D provided their HbA1c level from their most recent clinic visit, their self-reported general health, and completed a measure of diabetes self-care. RESULTS: Parent-reported family conflict was high, as was disease impact on family dynamics and parental stress. Higher HbA1c (poorer metabolic control) and less adequate adolescent self-care were associated with lower levels of family functioning, more adolescent behavioural difficulties and poorer adolescent mental health. CONCLUSIONS: The implication of these findings was discussed in relation to needs for information and support among Australian families with an adolescent with T1D, acknowledging the important dimension of family functioning and relationships in adolescent chronic disease management.
Health and Quality of Life Outcomes 03/2013; 11(1):50. · 2.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is increasing evidence for glucose fluctuation playing a role in the damaging effects of diabetes on various organs, including the brain. We aimed to study the effects of glycaemic variation (GV) upon mitochondrial activity using an in vitro human neuronal model. The metabolic disturbance of GV in neuronal cells, was mimicked via exposure of neuroblastoma cells SH-SY5Y to constant glucose or fluctuating (i.e. 6 h cycles) for 24 and 48 h. Mitochondrial dehydrogenase activity was determined via MTT assay. Cell mitochondrial activity (MTT) was moderately decreased in constant high glucose, but markedly decreased following 24 and 48 h of cyclical glucose fluctuations. Glucose transport determined via 2-deoxy-D-[1-(14)C] glucose uptake was regulated in an exaggerated manner in response to glucose variance, accompanied by modest changes in GLUT 1 mRNA abundance. Osmotic components of these glucose effects were investigated in the presence of the osmotic-mimics mannitol and L: -glucose. Both treatments showed that fluctuating osmolality did not result in a significant change in mitochondrial activity and had no effects on (14)Cglucose uptake, suggesting that adverse effects on mitochondrial function were specifically related to metabolically active glucose fluctuations. Apoptosis gene expression showed that both intrinsic and extrinsic apoptotic pathways were modulated by glucose variance, with two major response clusters corresponding to (i) glucose stress-modulated genes, (ii) glucose mediated osmotic stress-modulated genes. Gene clustering analysis by STRING showed that most of the glucose stress-modulated genes were components of the intrinsic/mitochondrial apoptotic pathway including Bcl-2, Caspases and apoptosis executors. On the other hand the glucose mediated osmotic stress-modulated genes were mostly within the extrinsic apoptotic pathway, including TNF receptor and their ligands and adaptors/activators/initiators of apoptosis. Fluctuating glucose levels have a greater adverse effect on neuronal cell energy regulation mechanisms than either sustained high or low glucose levels.
Neurochemical Research 05/2012; 37(8):1768-82. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Screening tests of basic cognitive status or 'mental state' have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. OBJECTIVE: We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. METHODS: Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. RESULTS: Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). CONCLUSIONS: Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae.
[show abstract][hide abstract] ABSTRACT: 2 Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain.
Type 1 diabetes, N = 79 (mean age 20.32 ± 4.24 years), and healthy control participants, N = 50 (mean age 20.53 ± 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient.
Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age-related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time.
We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified.
Diabetes care 03/2012; 35(3):513-9. · 7.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with Cystic Fibrosis (CF) are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability.
Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well.
Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77). At the follow up OGTT, 8 of 9 (89%) remained within their respective glucose tolerance status groupings.
The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.
PLoS ONE 01/2012; 7(9):e44844. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine possible determinants of autoantibody levels at type 1 diabetes mellitus (T1DM) onset.We assessed levels of glutamic acid decarboxylase 65 islet cell antigen (GADA) and anti-insulin antibodies (IAA) in 247 incident T1DM cases presenting <15 years of age in Melbourne from 1st March 2008 to 30th June 2010.58.9% (142/241) of cases were GADA seropositive and 42.3% (94/222) were IAA seropositive. Factors associated with elevated IAA antibodies included younger age and red hair phenotype. Factors associated with elevated GAD antibodies included lower birthweight and recent eczema. Intriguingly, low recent or past sun exposure was only associated with elevated GADA levels among children presenting at age <5 years, not older (difference in effect, p<0.05 for 4 of 5 associations).These findings show that environmental and phenotypic factors are associated with autoantibody levels at time of presentation for T1DM. We recommend such environmental and phenoytypic factors should be examined in further detail.
[show abstract][hide abstract] ABSTRACT: The pathophysiology of cerebral oedema (CE) in diabetic ketoacidosis (DKA) remains enigmatic. We investigated the role of the idiogenic osmol taurine and aquaporin channels in an in vitro model, the SH-SY5Y neuroblastoma cell line, by sequentially mimicking DKA-like hyperglycemia/hypertonicity and hypotonic fluid therapy. Exposure to DKA-like hyperosmolarity led to shrinkage, while hypotonic fluid exposure led to cell swelling and impaired viability. Low sodium compensated in part for elevated glucose, pointing to a critical role for overall osmolality. Taurine, was synthesized and retained intracellularly during DKA-like hypertonicity, and released during hypotonicity, in part mitigating neuronal swelling. Metabolic labeling showed that the rate of taurine release was inadequate to fully prevent neuronal swelling during hypotonic fluid therapy following DKA-like hypertonicity. Under these conditions, Aquaporin4 & 9 channels were respectively down and up-regulated. Our study provides further novel insights into molecular mechanisms contributing to CE in DKA and its therapy.
Neurochemical Research 09/2011; 37(1):182-92. · 2.13 Impact Factor
[show abstract][hide abstract] 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.
Diabetic Medicine 09/2011; 28(9):1109-12. · 3.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few qualitative studies have examined the views of adolescents with type 1 diabetes mellitus (T1DM) regarding psychosocial programme development and content. We conducted focus groups with 13 adolescents with T1DM to explore stressors and gain feedback on adapting a generic coping skills programme. The following prevalent stressors were identified: parental/adolescent conflict, balancing self-management and daily life, and health concerns. Prevalent views on programme adaptation included enhancing social support and adding diabetes-specific information and skills. Based on these data, the programme was adapted to address stressors and support self-management, thus better meeting the needs of, and appeal to, adolescents with T1DM.
Journal of Health Psychology 08/2011; 17(3):313-23. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Higher birthweight is associated with increased type 1 diabetes mellitus (T1DM) risk, but the contribution of higher adiposity or lean mass is unclear. In this Tasmanian infant cohort, early upper respiratory infection has been associated with higher asthma risk.
Eligible infants represented one-fifth of live births in Tasmania, 1988-1995. Hospital interview data (day 6) were obtained on 96.3% (10 628/11 040), home (5 wk) visit data (38 d) on 92.9% (9876/10 628) of those, then a phone (12 wk) interview (87 d). Tricep and subscapular skinfold measures and upper arm circumference were recorded at the first two interviews. T1DM cases (n = 26) arising from the age of 16 or under in Tasmania from 1988 to 2006 were ascertained.
Higher birthweight [adjusted odds ratio (AOR) 2.82 (95% CI 1.31-6.09)], lean mid-upper arm circumference [AOR 1.76 (95% CI 1.16-2.66)], not skinfold measures, were associated with T1DM risk. Children with an early upper respiratory tract infection by 5-wk visit [AOR 2.74 (95% CI 1.19-6.32)] or ear infection by 12-wk interview [AOR 3.44 (95% CI 1.00-11.79)] were also at higher risk. Putative markers of altered microbial exposure such as resident density were not associated with T1DM risk but the effect of increasing birth order on T1DM risk differed for older (AOR 0.41, p = 0.02) than young mother (AOR 2.45, p = 0.01); difference in effect, p = 0.001.
In this cohort, early upper respiratory tract infection was associated with T1DM risk, as had been previously found for asthma, consistent with immunoinflammatory upregulation. Using the detailed anthropometric measures available, the link between higher birthweight and T1DM did not appear to reflect increased adiposity.
[show abstract][hide abstract] ABSTRACT: Many young people experience improved glycemia with continuous subcutaneous insulin infusion (CSII) regimens; however, sustained glycemic benefit eludes a significant proportion. Our aims were to assess adherence to recommended CSII-related behaviors in a representative pediatric cohort and to identify potentially modifiable behaviors that impact on HbA1c in youth.
Data uploaded from insulin pump devices of 100 youth with type 1 diabetes were analyzed.
Ability to translate recommended behaviors into daily self-management varied widely in youth. Mean bolus frequency was 6.1/d; however, 69/100 entered <4 blood glucose levels (BGL)/d. HbA1c decreased by 0.2% for each additional BGL (p=0.001) and bolus event (p<0.001) per day. Prandial insulin omission was common and associated with significantly increased HbA1c. On average, if breakfast insulin was missed ≥4 times per fortnight, HbA1c increased 1.0% (p<0.001). If one or more days per fortnight with ≤2 food boluses/d were recorded, then HbA1c increased 0.8% (p=0.001). Increasing age and duration of CSII correlated with poorer adherence to recommended behaviors.
Glycemic advantage obtained with CSII regimens is closely related to the manner in which CSII is employed. Poor adherence to integral CSII-related tasks is frequently encountered in adolescents and limits the efficacy of CSII in these youth.
[show abstract][hide abstract] ABSTRACT: This study evaluated the impact on quality of life (QoL) of an algorithm guiding the responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetes (T1D) patients using real-time (RT)-continuous glucose monitoring (CGM).
Sixty CSII-treated T1D participants (13-70 years old, glycosylated hemoglobin [HbA1c] ≤ 9.5%), including adult and adolescent subgroups, were randomized in age-, gender-, and HbA1c-matched pairs. Phase 1 was an open 16-week multicenter randomized controlled trial; Group A received CSII/RT-CGM with the algorithm, and Group B received CSII/RT-CGM without algorithm. Phase 2 was the 16-32-week follow-up study; Group A returned to usual care (CSII without RT-CGM), and Group B was provided with algorithm at 16 weeks. QoL was assessed by DQOL (adults) and DQOLY (adolescents) questionnaires at baseline, 16 weeks, and 32 weeks. Higher scores (range 1-5) indicate poorer QoL. Analysis was by analysis of variance (between group for baseline-16 weeks) and paired two-tailed t tests (within group for baseline and 32 weeks) with significance at P < 0.05.
Withdrawals left 28 of 30 patients in Group A and 27 of 30 patients in Group B at 32 weeks. In Phase 1, QoL in Group A (2.16 [0.44] baseline to 1.86 [0.40] at 16 weeks) improved compared with Group B (2.03 [0.47] to 2.03 [0.50]) (P = 0.002). Change in QoL correlated with changes in HbA1c (R = 0.36; P = 0.007). In Phase 2, Group A QoL was better at 32 weeks compared with baseline (2.16 [0.44] vs. 2.02 [0.43]) (P = 0.04) but was not in Group B (2.03 [0.47] vs. 1.99 [0.51]) (P = not significant).
An algorithm guiding CSII-treated T1D responses to RT-CGM improved QoL, which persisted post-RT-CGM withdrawal. Algorithm provision at RT-CGM initiation was required to benefit QoL.
[show abstract][hide abstract] ABSTRACT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.
The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas.
This study was an international, multicenter, retrospective case collection/database analysis.
The study was conducted at 36 tertiary referral endocrine and clinical genetics departments.
Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls.
The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy.
AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.
The Journal of clinical endocrinology and metabolism 11/2010; 95(11):E373-83. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Studies of siblings of children with Type 1 diabetes (Type 1 DM) have shown either increased levels of maladjustment or, alternatively, increased levels of pro-social behaviour according to whether the sibling or parent was interviewed. The purpose of this study was to examine the psychological adjustment of Type 1 DM siblings using both parent and sibling report and to assess the concordance between child and parent reports.
Ninety-nine siblings aged 11-17 years and parents of children with Type 1 DM treated at the Royal Children's Hospital, Melbourne were recruited sequentially. The Strengths and Difficulties Questionnaire (SDQ) was used to assess well siblings' emotional and behavioural functioning using data collected within a semi-structured interview. SDQ data between the sibling cohort and normative data sample were compared using independent-samples t-tests. Sibling reports and parent reports were compared using a series of paired-sample t-tests and correlation analyses.
Type 1 DM siblings did not report greater emotional or behavioural maladjustment or more pro-social behaviour than norms. Parents rated siblings' pro-social behaviour as being comparable with that of youth from the general community; however, parents rated healthy siblings as having lower levels of maladjustment; specifically, significantly fewer conduct problems, hyperactive behaviour and peer-related problems (all P < 0.01). There were no significant differences between parent ratings and sibling ratings on peer-related problems or pro-social behaviour.
Type 1 DM siblings did not report increased behavioural or emotional dysfunction relative to children in the general population and, according to their parents, were even better adjusted than their peers.
Diabetic Medicine 09/2010; 27(9):1084-7. · 3.24 Impact Factor