Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up.

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.

The effect of type 1 diabetes on the developing brain.

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.

Evolution of Depression and Anxiety Symptoms in Parents of Very Preterm Infants During the Newborn Period.

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.

A randomized controlled trial of cognitive behaviour therapy to improve glycaemic control and psychosocial wellbeing in adolescents with type 1 diabetes.

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).

Diabetic ketoacidosis and electroencephalographic changes in newly diagnosed pediatric patients.

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.

Risk factors for decline in IQ in youth with type 1 diabetes over the 12 years from diagnosis/illness onset.

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.

Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children.

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.

Improving mental health of adolescents with Type 1 diabetes: protocol for a randomized controlled trial of the Nothing Ventured Nothing Gained online adolescent and parenting support intervention.

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.

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes.

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.

Can the home environment promote resilience for children born very preterm in the context of social and medical risk?

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.

Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes.

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.

Psychosocial well-being and functional outcomes in youth with type 1 diabetes 12 years after disease onset.

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.

Neuropsychological profiles of young people with type 1 diabetes 12 yr after disease onset.

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.

Central nervous system function in youth with type 1 diabetes 12 years after disease onset.

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.

Hyperglycemia and externalizing behavior in children with type 1 diabetes.

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.

Therapy insight: the impact of type 1 diabetes on brain development and function.

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.