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Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes.

ABSTRACT: Sustained dysregulation of blood glucose (hyper- or hypoglycemia) associated with type 1 diabetes (T1D) has been linked to cognitive deficits and altered brain anatomy and connectivity. However, a significant gap remains with respect to how T1D affects spontaneous at-rest connectivity in young developing brains. Here, using a large multisite study, resting-state functional MRI data were examined in young children with T1D (n = 57; mean age = 7.88 years; 27 females) as compared with age-matched control subjects without diabetes (n = 26; mean age = 7.43 years; 14 females). Using both model-driven seed-based analysis and model-free independent component analysis and controlling for age, data acquisition site, and sex, converging results were obtained, suggesting increased connectivity in young children with T1D as compared with control subjects without diabetes. Further, increased connectivity in children with T1D was observed to be positively associated with cognitive functioning. The observed positive association of connectivity with cognitive functioning in T1D, without overall group differences in cognitive function, suggests a putative compensatory role of hyperintrinsic connectivity in the brain in children with this condition. Altogether, our study attempts to fill a critical gap in knowledge regarding how dysglycemia in T1D might affect the brain's intrinsic connectivity at very young ages.

SUBMITTER: Saggar M

PROVIDER: S-EPMC5319714 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes.

Saggar Manish M Tsalikian Eva E Mauras Nelly N Mazaika Paul P White Neil H NH Weinzimer Stuart S Buckingham Bruce B Hershey Tamara T Reiss Allan L AL

Diabetes 20161004 3

Sustained dysregulation of blood glucose (hyper- or hypoglycemia) associated with type 1 diabetes (T1D) has been linked to cognitive deficits and altered brain anatomy and connectivity. However, a significant gap remains with respect to how T1D affects spontaneous at-rest connectivity in young developing brains. Here, using a large multisite study, resting-state functional MRI data were examined in young children with T1D (<i>n</i> = 57; mean age = 7.88 years; 27 females) as compared with age-ma ...[more]

PMID: 27702833

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Project description:BackgroundClosed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear.MethodsIn this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes.ResultsA total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group.ConclusionsIn this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

Project description:BACKGROUND: Many children with type 1 diabetes have poor glycaemic control. Since the Diabetes Control and Complications Trial (DCCT) showed that tighter control reduces complication rates, there has been more emphasis on intensified insulin therapy. We know that patients and families are afraid of hypoglycaemia. We hypothesised that fear of hypoglycaemia might take precedence over concern about long-term complications, and that behaviour to avoid hypoglycaemia might be at the cost of poorer control, and aimed to evaluate the effectiveness of any interventions designed to prevent that. The objective of this review was to systematically review studies concerning the extent and consequences of fear of hypoglycaemia in parents of children under 12 years of age with type 1 diabetes, and interventions to reduce it. METHODS: DATA SOURCES: MEDLINE, EMBASE, PsycINFO, The Cochrane Library, Web of Science, meeting abstracts of EASD, ADA and Diabetes UK, Current Controlled Trials, ClinicalTrials.gov, UK CRN, scrutiny of bibliographies of retrieved papers and contact with experts in the field.Inclusions: Relevant studies of any design of parents of children under 12 years of age with Type 1 diabetes were included. The key outcomes were the extent and impact of fear, hypoglycaemia avoidance behaviour in parents due to parental fear of hypoglycaemia in their children, the effect on diabetes control, and the impact of interventions to reduce this fear and hypoglycaemia avoidance behaviour. RESULTS: Eight articles from six studies met the inclusion criteria. All were cross sectional studies and most were of good quality. Parental fear of hypoglycaemia, anxiety and depression were reported to be common. There was a paucity of evidence on behaviour to avoid hypoglycaemia, but there were some suggestions that higher than desirable blood glucose levels might be permitted in order to avoid hypoglycaemia. No studies reporting interventions to reduce parental fear of hypoglycaemia were found. CONCLUSIONS: The evidence base was limited. Parents of children with Type 1 diabetes reported considerable parental fear of hypoglycaemia, affecting both parental health and quality of life. There is some suggestion that hypoglycaemia avoidance behaviours by parents might adversely affect glycaemic control. Trials of interventions to reduce parental anxiety and hypoglycaemia avoidance behaviour are needed. We suggest that there should be a trial of structured education for parents of young children with Type 1 diabetes.

Project description:BackgroundYoung children are susceptible to enterovirus (EV) infections, which cause significant morbidity in this age group. However, the current knowledge regarding the epidemiology of EVs and the circulating virus strains is mostly based on viruses detected in children with severe diseases leading to contact with the health care system, while the vast reservoir of EVs that circulate in the general population is less characterized.MethodologyThe present study investigates the types and the prevalence of EVs circulating in the young children of the background population in Georgia, Colorado, and Washington State in the USA, and Germany, Sweden, and Finland in Europe. A total of 4018 stool samples, collected monthly from 300 healthy and non-hospitalized children at the age of 3-18 months in 2005-2009, were analyzed for the presence of EVs using RT-PCR, followed by sequencing of the VP1-2A region of the viral genome to type the EV(s) present. All of the children carried type HLA-DQ2 or -DQ8 alleles associated with type 1 diabetes.Principal findingsAltogether 201 children (67%) were found to be EV positive. The prevalence was much lower in Finnish children (26%) than in the children of the other counties combined (75%). Infections increased by age and showed a nadir during the winter months. Children who carried both the HLA-DQ2 and -DQ8 alleles had less infections than children who were homozygous for these alleles. Coxsackieviruses type A were the most frequently detected viruses in all geographical regions. Coxsackievirus type A4, Echovirus type 18, and Echovirus type 25 were shed for longer time periods than the other EV types.ConclusionsCompared to prevalence data from symptomatic patients requiring medical attention, this study provides a better view of EVs circulating in young children in the USA and in Europe. The observations may prove useful for the selection of strategies for designing EV vaccines in the future. The study also confirms our previous serological findings suggesting that EV infections are relatively rare in Finland.

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Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes.

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Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes.

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