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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: 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.

In the post-DCCT (Diabetes Control and Complications Trial) (1) and -EDIC (Epidemiology of Diabetes Interventions and Complications) (2) eras, considerable effort has been expended on early detection and treatment of diabetes-related microvascular complications in youth using screening programs. Numerous consensus statements have been generated relating to the timing, frequency, and content of such programs (3–7). Although each recommends a slightly different approach to screening, the same basic principles apply—achieve and maintain excellent glycemic control; reduce known and modifiable risk factors, such as smoking, obesity, hyperlipidemia, and hypertension; and screen for nephropathy and retinopathy on a regular basis following the inset of puberty. To be considered successful, any screening program must satisfy several criteria (8): Certainly, given what we know about microvascular complications and their progression and treatment, universal diabetes complication screening programs satisfy most of these prerequisites. Ten years after the DCCT, average levels of metabolic control have improved in most clinical reports of children and adolescents with type 1 diabetes, although population-based data remain scanty and perhaps less optimistic (9–14). Contemporary clinic-based reports of microvascular complication rates in adolescence have shown a concomitant improvement (15–18). On the other hand, reports relating to health-related quality of life (HRQOL) and psychological outcomes have been distressingly suboptimal (19–24). Although not all studies report significant associations (25–27), there are a number of reports showing that psychosocial dysfunction and family conflict are close correlates of poor health …

Shan and Ji (1) question the reliability of the association between a decline in performance intelligence quotient (PIQ) and younger age of type 1 diabetes (T1D) onset, which we recently reported from our longitudinal study of youth with T1D and healthy controls (HCs) (2). They suggest that if there is a significant association between decline in PIQ and age of onset, then there should also be a significant difference for change in PIQ between participants with T1D and HCs. They also suggest that the association between decline in PIQ and younger age of T1D onset might be attributed to known age-related changes in IQ from adolescence to adulthood or other factors, such as the researcher conducting the tests or the emotional and physical state of participants. We address each of these concerns in turn. Shan and Ji suggest …

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.

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.

We agree with de Wit and Snoek's emphasis on the importance of discriminating between mental health screening in individuals and monitoring of health-related quality …