Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children With Type 1 Diabetes: Association With Hyperglycemia
2015; 64 (5): 1770-1779
A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.
2014; 37 (7): 1885-1891
Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.
View details for DOI 10.2337/db14-1445
View details for Web of Science ID 000353431200032
View details for PubMedID 25488901
A Randomized Trial of a Home System to Reduce Nocturnal Hypoglycemia in Type 1 Diabetes
2014; 37 (7): 1885-1891
Alterations in white matter structure in young children with type 1 diabetes.
2014; 37 (2): 332-340
Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.
View details for DOI 10.2337/dc13-2159
View details for PubMedID 24804697
High success rates of sedation-free brain MRI scanning in young children using simple subject preparation protocols with and without a commercial mock scanner-the Diabetes Research in Children Network (DirecNet) experience
2014; 44 (2): 181-186
OBJECTIVE To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children. RESEARCH DESIGN AND METHODS Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition. RESULTS Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects. CONCLUSIONS These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.
View details for DOI 10.2337/dc13-1388
View details for PubMedID 24319123
Cognitive Functioning in Young Children with Type 1 Diabetes
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
2014; 20 (2): 238-247
The ability to lie still in an MRI scanner is essential for obtaining usable image data. To reduce motion, young children are often sedated, adding significant cost and risk.We assessed the feasibility of using a simple and affordable behavioral desensitization program to yield high-quality brain MRI scans in sedation-free children.222 children (4-9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls, participated in a multi-site study focused on effects of type 1 diabetes on the developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were performed. All children underwent behavioral training and practice MRI sessions using either a commercial MRI simulator or an inexpensive mock scanner consisting of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel of the MRI scanner.205 children (92.3%), mean age 7 ± 1.7 years had high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans after the first scan session. With a second scan session, success rates were 100% and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did not differ between children with type 1 diabetes and children without diabetes, or between centers using a commercial MRI scan simulator and those using the inexpensive mock scanner.Behavioral training can lead to a high success rate for obtaining high-quality T1-and diffusion-weighted brain images from a young population without sedation.
View details for DOI 10.1007/s00247-013-2798-7
View details for Web of Science ID 000330987900007
View details for PubMedID 24096802
Real-Time Continuous Glucose Monitoring Systems in the Classroom/School Environment
DIABETES TECHNOLOGY & THERAPEUTICS
2013; 15 (5): 409-412
The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. (JINS, 2014, 20, 238-247).
View details for DOI 10.1017/S1355617713001434
View details for Web of Science ID 000332448700013
View details for PubMedID 24512675
White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study
2012; 35 (11): 2167-2173
Abstract Background: Children with type 1 diabetes (T1D) spend 4-7 h/day in school with very little supervision of their diabetes management. Therefore, families have become more dependent on technology, such as use of real-time continuous glucose monitoring (RT-CGM), to provide increased supervision of their diabetes management. We sought to assess the impact of RT-CGM use in the classroom/school environment. Subjects and Methods: Children with T1D using RT-CGM, their parents, and teachers completed a questionnaire about RT-CGM in the classroom/school environment. Results: The RT-CGM was tolerated well in the classroom/school environment. Seventy percent of parents, 75% of students, and 51% of teachers found RT-CGM useful in the classroom/school environment. The students found the device to be more disruptive than did their parents and teachers. However, all three groups agreed that RT-CGM increased their comfort with diabetes management at school. Conclusions: Our study suggests that RT-CGM is useful and not disruptive in the classroom/school environment. The development of education materials for teachers could further increase its acceptance in the classroom/school environment.
View details for DOI 10.1089/dia.2012.0314
View details for Web of Science ID 000318477700008
View details for PubMedID 23530577
Analysis of the NovoTwist pen needle in comparison with conventional screw-thread needles.
Journal of diabetes science and technology
2011; 5 (6): 1488-1489
To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.
View details for DOI 10.2337/dc12-0017
View details for Web of Science ID 000311424100015
View details for PubMedID 22966090
The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children
2011; 34 (7): 1458-1462
Administration of insulin via a pen device may be advantageous over a vial and syringe system. Hofman and colleagues introduce a new insulin pen needle, the NovoTwist, to simplify injections to a small group of children and adolescents. Their overall preferences and evaluation of the handling of the needle are reported in the study. This new needle has the potential to ease administration of insulin via a pen device that may increase both the use of a pen device and adherence to insulin therapy.
View details for PubMedID 22226270
Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
2010; 39 (3): 609-?
To determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy.In this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain.NP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children. A significant negative relationship between HbA1c and Wechsler Intelligence Scale for Children (WISC) verbal comprehension was observed. WISC index scores were significantly reduced in type 1 diabetic subjects who had experienced seizures. White matter volume did not show the expected increase with age in children with type 1 diabetes compared with HC children (diagnosis by age interaction, P=0.005). A similar trend was detected for hippocampal volume. Children with type 1 diabetes who had experienced seizures showed significantly reduced gray matter and white matter volumes relative to children with type 1 diabetes who had not experienced seizures.It is feasible to perform MRI and NP testing in young children with type 1 diabetes. Further, early signs of neuroanatomic variation may be present in this population. Larger cross-sectional and longitudinal studies of neurocognitive function and neuroanatomy are needed to define the effect of type 1 diabetes on the developing brain.
View details for DOI 10.2337/dc10-2164
View details for Web of Science ID 000293261200003
View details for PubMedID 21562318
Metformin Extended Release Treatment of Adolescent Obesity A 48-Week Randomized, Double-Blind, Placebo-Controlled Trial With 48-Week Follow-up
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
2010; 164 (2): 116-123
This article reviews current pump and continuous glucose monitoring therapy and what will be required to integrate these systems into closed-loop control. Issues with sensor accuracy, lag time, and calibration are discussed as well as issues with insulin pharmacodynamics, which result in a delayed onset of insulin action in a closed-loop system. A stepwise approach to closed-loop therapy is anticipated, where the first systems will suspend insulin delivery based on actual or predicted hypoglycemia. Subsequent systems may control to range, limiting the time spent in hyperglycemia by mitigating the effects of a missed food bolus or underestimate of consumed carbohydrates, while minimizing the risk of hypoglycemia.
View details for DOI 10.1016/j.ecl.2010.05.005
View details for Web of Science ID 000282146100011
View details for PubMedID 20723823
Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported.To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo.Multicenter, randomized, double-blind, placebo-controlled clinical trial.The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007.Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo.After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed.Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program.clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.
View details for Web of Science ID 000274139500001
View details for PubMedID 20124139