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Objective: 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.Research Design and Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Northam EA, Lin A. Hypoglycaemia in childhood onset type 1 diabetes -part villain, but not the only one. [ABSTRACT FROM AUTHOR]

AIMS: To describe psychiatric status and relationship to metabolic control in adolescents with Type 1 diabetes studied prospectively from diagnosis. METHODS: Adolescents (n = 41) completed a self-report measure of psychiatric status 10 years after disease onset. Metabolic control information was recorded prospectively from diagnosis. The rate and type of psychiatric disorder were determined and the relationship between mental health status and metabolic control history examined. RESULTS: Thirty-seven per cent of the adolescents met criteria for a DSM-IV psychiatric disorder, two to three times higher than community levels of psychiatric morbidity. Females were significantly more likely to receive a diagnoses (chi2 = 4.98, P < 0.05). Two thirds of participants had experienced at least one serious hypoglycaemic episode and one third had a history of chronic poor metabolic control. DSM-IV diagnoses were present in half of those with a history of chronic poor control, one third of the hypoglycaemia group and one quarter of well controlled participants. Adolescents with a current Mood (t = -2.83, P < 0. 01), Anxiety (t = -3.77, P = 0.001) or Behaviour (t = 2.56, P < 0.05) disorder and those with a history of poorly controlled diabetes (F (2,29) = 5.4, P = 0.01) had higher externalizing behaviour problem scores at diagnosis than those without current disorder. CONCLUSIONS: Adolescents with Type 1 diabetes are at high risk for psychiatric disorder. Poorly controlled diabetes over the first 10 years of illness was associated with pre-existing behaviour problems at diagnosis and there was a trend for an association with current psychiatric status. [ABSTRACT FROM AUTHOR]

Aims: Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up., Methods: RCT of youth aged 7-15 years with T1D, at two tertiary paediatric centres. Participants were randomised to commence CSII or continue multiple daily injections (MDI). Behaviour, mood, cognition and HbA1c were assessed. Primary outcome was difference in parent-reported behaviour (BASC-2) at 4 months. After the 4-month RCT, MDI participants commenced CSII; outcomes were reassessed at +2 years., Results: Participating youth (n=101) were randomised to CSII (n=56) or MDI (n=45). Significant differences favouring CSII were found at 4 months in parent-reported behaviour problems (Cohen's d 0.41 (95% CI 0.004 to 0.795); p=0.048) and HbA1c (mean (95% CI) difference: 7 (2.3 to 11.7) mmol/mol (0.6% (0.2 to 1.0%); p=0.001)). Improvements from baseline were documented in mood and cognitive outcomes in both study groups over the 4-month RCT; however, no between-group differences were evident at 4 months. Sixteen of 76 (21%) participants completing assessments at +2 years had discontinued CSII. In n=60 still using CSII, measurements of behaviour, mood and HbA1c were comparable to baseline., Conclusions: Parent-reported behaviour problems and HbA1c, but not mood or neurocognitive outcomes, were clinically significantly lower with CSII, relative to MDI, after 4 months. Observational follow-up indicated no impact of treatment modality at +2 years, relative to baseline levels. Taken together, these data indicate that use of CSII alone does not comprehensively benefit neuropsychological outcomes in childhood T1D., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The effect of type 1 diabetes on the developing brain is a topic of primary research interest. A variety of potential dysglycaemic insults to the brain can cause cellular and structural injury and lead to altered neuropsychological outcomes. These outcomes might be subtle in terms of cognition but appear to persist into adult life. Age and circumstance at diagnosis appear to play a substantial role in potential CNS injury. A history of diabetic ketoacidosis and chronic hyperglycaemia appear to be more injurious than previously suspected, whereas a history of severe hypoglycaemia is perhaps less injurious. Neurocognitive deficits manifest across multiple cognitive domains, including executive function and speed of information processing. Some evidence suggests that subtle brain injury might directly contribute to psychological and mental health outcomes. Impaired executive function and mental health, in turn, could affect patients' adherence and the ability to make adaptive lifestyle choices. Impaired executive functioning creates a potential feedback loop of diabetic dysglycaemia leading to brain injury, further impaired executive function and mental health, which results in suboptimal adherence, and further dysglycaemia. Clinicians dealing with patients with suboptimal glycaemic outcomes should be aware of these potential issues., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: Mothers experience heightened depression and anxiety following very preterm (VPT) birth, but how these symptoms evolve during the first months after birth is unknown. Research on the psychological adjustment of fathers following VPT birth is limited., Objectives: To describe the trajectory and predictors of distress in parents of VPT infants during the first 12 weeks after birth, and to compare rates of depression and anxiety in parents of VPT infants with those in parents of healthy full-term (FT) infants shortly after birth and at 6 months' postnatal age., Design, Setting, and Participants: Longitudinal, prospective, follow-up cohort study of depression and anxiety symptoms in parents of VPT infants (<30 weeks' gestational age; admitted to the neonatal intensive care unit at the Royal Women's Hospital, Melbourne, Australia, between January 21, 2011, and December 23, 2013), documented every 2 weeks until age 12 weeks and at age 6 months, as well as in parents of healthy FT infants (≥37 weeks' gestational age; birth weight >2499 g; born at the Royal Women's Hospital between August 15, 2012, and March 26, 2014; not admitted to the neonatal nursery) shortly after birth and at age 6 months., Exposure: Birth of a VPT infant., Main Outcomes and Measures: Symptoms of depression (Center for Epidemiological Studies Depression Scale) and anxiety (Hospital Anxiety and Depression Scale)., Results: The study included 113 mothers (mean [SD] age at birth, 32.7 [5.3] years) and 101 fathers (mean [SD] age at birth, 34.7 [6.4] years) of 149 VPT infants (49% male; 84 singletons, 65 multiples; mean [SD] birth weight, 1021 [261] g) as well as 117 mothers (mean [SD] age at birth, 32.9 [4.8] years) and 110 fathers (mean [SD] age at birth, 35.9 [5.3] years) of 151 healthy FT infants (50% male; 149 singletons, 2 multiples; mean [SD] birth weight, 3503 [438] g). Mean scores and rates of depression and anxiety reduced over time for parents of VPT infants in the 12 weeks after birth: the mean (95% CI) change in depression score per week was -0.52 (-0.73 to -0.31; P < .001) for mothers and -0.39 (-0.56 to -0.21; P < .001) for fathers; the mean (95% CI) change in anxiety score per week was -0.16 (-0.26 to -0.05; P = .003) for mothers and -0.22 (-0.31 to -0.15; P < .001) for fathers. However, rates never dropped below 20%. Few perinatal or social risk factors predicted longitudinal changes in depression or anxiety. Compared with parents of FT infants, parents of VPT infants had higher rates of depression shortly after birth (mothers: 6% vs 40%; odds ratio [OR] = 9.9; 95% CI, 4.3 to 23.3; P < .001; fathers: 5% vs 36%; OR = 11.0; 95% CI, 4.1 to 29.6; P < .001) and at 6 months (mothers: 5% vs 14%; OR = 2.9; 95% CI, 1.0 to 8.2; P = .04; fathers: 6% vs 19%; OR = 3.4; 95% CI, 1.3 to 9.0; P = .01) as well as anxiety shortly after birth (mothers: 13% vs 48%; OR = 6.5; 95% CI, 3.3 to 12.6; P < .001; fathers: 10% vs 47%; OR = 7.8; 95% CI, 3.7 to 16.8; P < .001) and at 6 months (mothers: 14% vs 25%; OR = 2.1; 95% CI, 1.0 to 4.3; P = .05; fathers: 10% vs 20%; OR = 2.3; 95% CI, 1.0 to 5.3; P = .05)., Conclusions and Relevance: Mothers and fathers of VPT infants had elevated rates of depression and anxiety symptoms that declined over time, although remaining above expected levels throughout the newborn period and at 6 months.

Objective: To document electroencephalogram (EEG) changes and their correlation with clinical parameters in a newly diagnosed pediatric cohort of type 1 diabetes mellitus (T1DM) patients with and without diabetic ketoacidosis (DKA) and to define their medium term utility and significance., Research Design and Methods: Prospective longitudinal study of children presenting with T1DM. EEGs were performed within 24 h of diagnosis, day 5, and at 6 months post-diagnosis and reviewed by a neurologist blinded to clinical status. Severity of encephalopathy was graded from 1 to 5 using the Aoki and Lombroso encephalopathy scale. Cognitive abilities were assessed using standardized tests of attention, memory, and intelligence., Results: Eighty eight children were recruited; 34 presented with DKA. Abnormal background slowing was more often observed in the first 24 h in children with DKA (p = 0.01). Encephalopathy scores on day 1 correlated with initial pH, CO2 , HCO3 , base excess, respiratory rate, heart rate, diastolic blood pressure, and IV fluid intake (all parameters p < 0.05). EEG scores at day 1 did not correlate with contemporaneous mental state or cognition in the medium term., Conclusions: DKA was associated with significant clinical and neurophysiologic signs of brain dysfunction at presentation. While EEG is sensitive to the detection of encephalopathy in newly diagnosed T1DM, it has limited use in identifying children at risk of later cognitive deficits., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We evaluated a cognitive behaviour therapy-based programme to improve glycaemic control and psychosocial wellbeing in adolescents with type 1 diabetes. A total of 147 adolescents aged 13-16 years were randomized to the intervention (n = 73) or standard care (n = 74). The primary outcome was glycaemic control at 3 and 12 months post randomization, and secondary measures were stress, self-efficacy and quality of life. Mixed-effects regression models were used to assess differences in means between groups at each time point. There was little evidence of differences in glycaemic control between groups. However, psychosocial wellbeing improved in the intervention group compared to the control group. Recommendations for future programmes are discussed. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000368336)., (© The Author(s) 2014.)

Objective: This study examined illness-related change in intelligence quotient (IQ) in a cohort of youth with type 1 diabetes studied prospectively from disease onset in childhood to follow-up 12 years later in late adolescence/early adulthood., Research Design and Methods: Participants included type 1 diabetes patients (n = 95; mean age at follow-up 21.3 years) and healthy control participants (HCs; n = 67; mean age at follow-up 21.0 years) from a cohort followed prospectively. Measures included Wechsler Preschool and Primary Scale of Intelligence-Revised, Wechsler Intelligence Scale for Children-Revised, and Wechsler Abbreviated Scale of Intelligence and prospective collection of data on metabolic control history., Results: Young people with type 1 diabetes showed greater decline in verbal IQ (VIQ) and full-scale IQ (FSIQ), but not performance IQ (PIQ), than HCs. Within the diabetes group, a younger age at diabetes onset was associated with a decline in PIQ and FSIQ (P ≤ 0.001). A history of hypoglycemic seizures was associated with a decline in VIQ (P = 0.002). Long-term metabolic control was not associated with changes in IQ. Interaction terms were not significant, suggesting no moderating effect of one diabetes-related variable over another., Conclusions: The presence of diabetes may negatively influence some aspects of IQ over time. Specific illness risk factors, such as an earlier age of disease onset and a history of hypoglycemic seizures, appear to put the young person at greater risk. Academic progress of children identified as at risk should be monitored and educational supports provided if necessary., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function., Research Design and Methods: Patients aged 6-18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses., Results: Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes., Conclusions: DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term., (© 2014 by the American Diabetes Association.)

Background: Management of Type 1 diabetes comes with substantial personal and psychological demands particularly during adolescence, placing young people at significant risk for mental health problems. Supportive parenting can mitigate these risks, however the challenges associated with parenting a child with a chronic illness can interfere with a parent's capacity to parent effectively. Interventions that provide support for both the adolescent and their parents are needed to prevent mental health problems in adolescents; to support positive parent-adolescent relationships; and to empower young people to better self-manage their illness. This paper presents the research protocol for a study evaluating the efficacy of the Nothing Ventured Nothing Gained online adolescent and parenting intervention which 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., Discussion: 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.

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., (© 2012 John Wiley & Sons A/S.)

Relationships between the home environment and early developmental outcomes were examined in 166 children born very preterm in one tertiary maternity hospital to explore whether a more optimal home environment could promote resilience. In particular, we explored whether this effect was apparent over and above social risk and children's biological risk, as measured by cerebral white matter abnormality (WMA) evaluated using magnetic resonance imaging (MRI) at term-corrected age and length of hospital stay (LOS), and whether the effect of the home environment differed according to WMA. The home environment and social-emotional outcomes were assessed at 2years' corrected age using the Home Screening Questionnaire (HSQ) and the Infant-Toddler Social and Emotional Assessment (ITSEA). Children's cognitive and motor development was assessed using the Bayley Scales of Infant Development II. A more optimal home environment was associated with better cognitive and social-emotional development after adjusting for social risk, WMA, and LOS. Neonatal cerebral WMA moderated the relationship between the home environment and dysregulation problems only, such that the home environment had less effect on dysregulation for children with mild or moderate to severe WMA. The need to support parents to create an optimal home environment is discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: This study investigated whether continuous subcutaneous insulin infusion is associated with sustained improvement in behaviour and metabolic control., Methods: 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., Results: 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., Conclusions: 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., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims: 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., Methods: 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., Results: 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., Conclusions: 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.

Objective: Type 1 diabetes in youth and community controls were compared on functional outcomes. Relationships were examined between psychosocial variables at diagnosis and functional outcome 12 years later., Research Design and Methods: Participants were subjects with type 1 diabetes (n = 110, mean age 20.7 years, SD 4.3) and control subjects (n = 76, mean age 20.8 years, SD 4.0). The measures used included the Youth Self-Report and Young Adult Self-Report and a semi-structured interview of functional outcomes. Type 1 diabetes participants also provided information about current diabetes care and metabolic control from diagnosis., Results: Type 1 diabetes participants and control subjects reported similar levels of current well-being but for the youth with type 1 diabetes, the mental health referral rates over the previous 12 years were higher by 19% and school completion rates were lower by 17%. Over one-third of clinical participants were not currently receiving specialist care and this group had higher mental health service usage in the past (61 vs. 33%) and lower current psychosocial well- being. Within the type 1 diabetes group, behavior problems, high activity, and low family cohesion at diagnosis predicted lower current well-being, but were not associated with metabolic control history. Poorer metabolic control was associated with higher mental health service usage., Conclusions: Type 1 diabetes participants report similar levels of current psychosocial well-being compared with control subjects, but higher levels of psychiatric morbidity since diagnosis and lower school completion rates. Psychiatric morbidity was associated with poor metabolic control and failure to transition to tertiary adult diabetes care.

Background: Lowered neuropsychological performance is evident in youth with type 1 diabetes, although evidence for associations with specific illness variables is inconsistent. This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospectively from diagnosis 12 yr previously., Methods: A total of 106 youth with type 1 diabetes and 75 healthy controls participated. There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously, current socioeconomic status, gender distribution, or age. Neuropsychological tests assessed eight cognitive domains: verbal abilities, perceptual reasoning, new learning, working memory, non-verbal processing speed, mental efficiency, divided attention, and sustained attention. Episodes of serious hypoglycemia and HbA(1c) levels were recorded from diagnosis., Results: Youth with type 1 diabetes performed more poorly than controls on working memory (p < .05). Early onset diabetes was related to poorer sustained (p < .001) and divided attention (p = .001), new learning, and mental efficiency (both p < .05). Hypoglycemia was found to adversely effect verbal abilities, working memory, and non-verbal processing speed (all p < .05). Poorer working memory was associated with hyperglycemia (p < .05). Youth with any combination of two or three illness risk factors (i.e., early onset diabetes, hypo-, hyperglycemia), performed more poorly than controls and youth with no or one risk on verbal abilities, working memory, and mental efficiency., Conclusions: This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes. Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system, with hyperglycemia playing a lesser role.

Objective: In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis., Research Design and Methods: We studied type 1 diabetic (n = 106) and control subjects (n = 75) with no significant group difference on IQ at baseline 12 years previously by using the Wechsler Abbreviated Scale of General Intelligence, magnetic resonance spectroscopy and imaging, and metabolic control data from diagnosis., Results: Type 1 diabetic subjects had lower verbal and full scale IQs than control subjects (both P < 0.05). Type 1 diabetic subjects had lower N-acetylaspartate in frontal lobes and basal ganglia and higher myoinositol and choline in frontal and temporal lobes and basal ganglia than control subjects (all P < 0.05). Type 1 diabetic subjects, relative to control subjects, had decreased gray matter in bilateral thalami and right parahippocampal gyrus and insular cortex. White matter was decreased in bilateral parahippocampi, left temporal lobe, and middle frontal area (all P < 0.0005 uncorrected). T2 in type 1 diabetic subjects was increased in left superior temporal gyrus and decreased in bilateral lentiform nuclei, caudate nuclei and thalami, and right insular area (all P < 0.0005 uncorrected). Early-onset disease predicted lower performance IQ, and hypoglycemia was associated with lower verbal IQ and volume reduction in thalamus; poor metabolic control predicted elevated myoinositol and decreased T2 in thalamus; and older age predicted volume loss and T2 change in basal ganglia., Conclusions: This study documents brain effects 12 years after diagnosis in a type 1 diabetic sample whose IQ at diagnosis matched that of control subjects. Findings suggest several neuropathological processes including gliosis, demyelination, and altered osmolarity.

Objective: Ancedotally, parents report behavioral changes in their diabetic children who have fluctuating blood glucose levels. This study aimed to test associations between intercurrent glycemia and child behavior in an ambulant setting., Research Design and Methods: Prepubertal children attending the Royal Children's Hospital, Melbourne, Australia, with type 1 diabetes received glycemic assessment and simultaneous behavioral assessment on two occasions 6 months apart. Subjects wore a continuous glucose monitor over a 72-h period, and parents completed the Behavior Assessment System for Children at the two study time points., Results: There was a high correlation between intra-individual externalizing and internalizing behavior scores (r = 0.88, P < 0.001 and r = 0.81, P < 0.001, respectively) at the two time points. Mean blood glucose (MBG) was significantly associated with the mean externalizing behavior score (beta = 1.7 [95% CI 0.6-2.8], adjusted r(2) = 0.088). Percentage of time in the normal (r = -0.2 [-0.3 to -0.5], adjusted r(2) = 0.068) and high (r = 0.2 [0.07-0.3], adjusted r(2) = 0.089) glycemic ranges were significantly associated with the mean externalizing behavior score. For every 5% increase in time in the normal glycemic range, there was a decrease in the externalizing behavior score of 1.0, and for every 5% increase in time in the high glycemic range there was an increase in the externalizing behavior score of 1.0. There was no significant association between MBG and the mean internalizing behavior score., Conclusions: Externalizing behaviors were associated with intercurrent glycemic status. These findings underscore the importance of understanding the mechanisms of this association and how it might impact ultimate diabetes outcomes.

The incidence of Type 1 diabetes is increasing worldwide, imposing enormous public health costs, as well as profoundly affecting individual quality of life. There is evidence that psychological problems are increased in children with diabetes and this morbidity is often associated with poor metabolic control. Specific risk factors for this dual morbidity are emerging from empirical studies. The next challenge is to identify effective interventions for use with children at risk for adverse mental and physical health outcomes. The intervention literature is reviewed. It is noted that most studies have used diabetes-specific, unstandardized interventions in groups of adolescents, with few interventions trialled with younger children. No study has targeted a specific psychological disorder such as behaviour problems or depression, both of which are known to be increased in children with diabetes and for which effective standardized interventions are available. Attention is drawn to methodological limitations in many of the studies conducted to date and suggestions made to reduce these in future interventions attempting to reduce the burden of illness in children with diabetes.

The CNS is one of the main organ systems that is affected in type 1 diabetes, as both cerebral glucose and insulin levels are frequently abnormal, even when the diabetes is well-controlled. Literature is emerging that documents pathophysiological CNS changes and neurocognitive deficits in both adults and children with type 1 diabetes, but empirical findings to date have often been inconsistent and difficult to interpret. This article provides a comprehensive review of current knowledge about the impact of type 1 diabetes on brain development and function, focusing particularly on the evidence for specific illness-related risk factors for CNS sequelae. We argue that clinical management of young patients with type 1 diabetes should take into account current knowledge of the relative risks of hypoglycemia and hyperglycemia to the developing brain.

Contemporary outcome measures of chronic illnesses such as type 1 diabetes mellitus are broader than those clinical outcomes traditionally assessed in therapeutic encounters. A holistic approach emphasises quality of life and emotional well-being as well as the achievement of optimal disease management. This paper reviews current knowledge about growth, metabolic control, diabetes complications, neurocognitive and psychological outcomes as well as health-related quality of life in childhood diabetes mellitus. It is suggested that the antecedents of adverse diabetes and psychological outcomes in adolescence lie in the years prior to adolescence. The model of care in childhood diabetes mellitus must be focussed on earlier screening and intervention if adverse outcomes are to be reduced.

With advances in medical knowledge, many paediatric metabolic and endocrine disorders can now be treated effectively. The focus of clinical management has shifted from survival to quality of outcome for survivors. This paper refers to three conditions, congenital hypothyroidism, phenylketonuria and type 1 diabetes mellitus, to illustrate the effects of metabolic disturbances on the developing brain. Neuropsychological and psychosocial correlates of these disorders are reviewed. Current knowledge about illness-related predictors of outcome is also discussed.

Aims: To assess the validity of the Child Health Questionnaire (CHQ) as a screening tool for detecting 'at risk' emotional and behavioural maladjustment in children with diabetes, using the Behaviour Assessment System for Children (BASC) as a gold standard measure., Methods: CHQ and BASC were administered to 103 parents of children with Type 1 diabetes, aged 7-12 years. Sub-scales of the two measures were compared using Pearson's bivariate correlations. CHQ sensitivity and specificity cut-points were optimized against the BASC borderline category using receiver operating characteristic curves., Results: The BASC Externalizing Problems scale correlated strongly with CHQ Behaviour, Global Behaviour, Mental Health, Family Activities and Family Cohesion scales (r-values -0.68, -0.54, -0.51, -0.59, and -0.42, respectively). BASC Internalizing Problems scale correlated strongly with CHQ Behaviour, Mental Health and Family Cohesion scales (r-values -0.40, -0.43 and -0.45, respectively). Using receiver operating characteristic curve analysis, the CHQ Mental Health scale most effectively identified children classified as borderline on the BASC Internalizing Problems scale (sensitivity 87%, specificity 78%), while the CHQ Global Behaviour scale most effectively identified children classified as borderline on the BASC Externalizing Problems scale (sensitivity 73%, specificity 82%)., Conclusions: Significant correlations were seen between the CHQ Global Behaviour and Mental Health scales and the BASC Externalizing and Internalizing scales, respectively. Sequential use of the CHQ, as a screening tool, followed by an established mental health measure such as the BASC, may help identify children with diabetes 'at risk' for chronic maladjustment and poor health outcomes.

Objective: To describe neuropsychological profiles and their relationship to metabolic control in children with type 1 diabetes 6 years after the onset of disease., Research Design and Methods: Children with type 1 diabetes (n = 90), aged 6-17 years, who had previously been assessed soon after diagnosis and 2 years later, were reevaluated 6 years after the onset of disease. Their neuropsychological profiles were compared with those of individuals in a community control group (n = 84), who had been assessed at similar intervals. Relationships between illness variables, such as age at the onset of disease and metabolic control history, and neuropsychological status were also examined., Results: Six years after onset of disease, children with type 1 diabetes performed more poorly than control subjects on measures of intelligence, attention, processing speed, long-term memory, and executive skills. Attention, processing speed, and executive skills were particularly affected in children with onset of disease before 4 years of age, whereas severe hypoglycemia was associated with lower verbal and full-scale intelligence quotient scores., Conclusions: Neuropsychological profiles of children with type 1 diabetes 6 years after the onset of disease are consistent with subtle compromise of anterior and medial temporal brain regions. Severe hypoglycemia, particularly in very young children, is the most plausible explanation for neuropsychological deficits, but the contributory role of chronic hyperglycemia warrants further exploration.

Objective: To identify type 1 diabetes-related predictors of change in the neuropsychological profiles of children over the first 2 years of the illness., Research Design and Methods: Children (n = 116) aged 3-14 years were assessed soon after diagnosis and re-evaluated 2 years later to examine relationships between illness variables, such as age of onset and metabolic control history, and changes in neuropsychological status over the first 2 years of type 1 diabetes., Results: Illness variables were significant predictors of change in neuropsychological test scores within 2 years of onset of type 1 diabetes. Age of onset of type 1 diabetes predicted negative change on Performance Intelligence Quotient, whereas both recurrent severe hypoglycemia and chronic hyperglycemia were associated with reduced memory and learning capacity., Conclusions: These results suggest that the relationship between metabolic control and neuropsychological risk is nonlinear in that children with either recurrent severe hypoglycemia or chronically elevated blood sugars exhibit negative changes in their neuropsychological profiles. Onset of type 1 diabetes very early in life adds another dimension of risk, particularly affecting the acquisition of visuospatial skills.

Objective: To compare the neuropsychological profiles of children with IDDM with a community control group at two time points: 3 months after disease onset and 2 years after the baseline assessment., Research Design and Methods: A total of 123 children (age 3-14 years) with recent IDDM onset were compared with 129 community control subjects, stratified for age and sex, on standardized measures of general intelligence, attention, speed of processing, memory, learning, executive skills, and behavioral adjustment soon after diagnosis and 2 years later. Exclusion criteria were premorbid evidence of central nervous system disease or trauma, or English not spoken in the home., Results: There were no differences between children with IDDM and control subjects on any measure at the initial assessment 3 months after disease onset. Two years later, children with IDDM tended to show a less positive change, relative to control subjects, in their standardized scores on measures of general intelligence, and significantly so on the vocabulary (P < 0.01) and block design (P < 0.05) subtests. Multivariate group differences were also apparent on speed of processing (P < 0.05) and learning (P < 0.01) subtests, reflecting smaller developmental gains in the children with IDDM when compared with control subjects., Conclusions: The findings are consistent with previous reports, suggesting that IDDM is associated with an increased risk of mild neuropsychological dysfunction. The skills most affected in this cohort were information processing speed, acquisition of new knowledge, and conceptual reasoning abilities. Clinicians and educators should be made aware of the risk of specific neuropsychological deficits in children with IDDM.