Intensive therapy is now accepted as the current standard of care in diabetes. However, intensive therapy is frequently complicated by hypoglycemia, which then becomes a limiting factor in maintaining glucose control. During intensive treatment, hypoglycemia occurs in patients with diabetes due to excess insulin, 'excess glucose utilization (e.g. exercise) or inadequate carbohydrate intake. Young children and adolescents have many lifestyle characteristics that make them particularly prone to hypoglycemia. In addition, frequent hypoglycemia may lead to neurological sequelae. With current home glucose monitoring capabilities it is difficult to accurately define the true incidence, duration and severity of hypoglycemia. Continuous glucose monitoring (CGM) has recently become available as a tool to more closely examine glucose patterns and defining characteristics of hypoglycemia, so that measures for prevention of hypoglycemia can be devised. Recent neurocognitive and neuro-imaging studies show that the developing brain may be particularly vulnerable to hypoglycemia. The understanding of specific neurocognitive deficits requires further studies in children and young adults. Optimal prevention of hypoglycemia and its sequelae requires near-continuous recognition and response to prevailing blood glucose concentrations. Hence, our major objective is to use CGM to detect the frequency, severity and duration of hypoglycemia and then carry out a randomized controlled trial (RCT) to determine the ability of real-time CGM to minimize the risk of hypoglycemia in young patients with type 1 diabetes (T1DM) ages 7-24. In addition we will examine added variables of intervention with activity assessment, diet or both, to determine if further reductions in hypoglycemia are achievable. At baseline, we will compare rates of hypoglycemia frequency, severity and duration and other factors, such as age at onset or duration of diabetes, with neurocognitive and neuroimaging parameters in a cross-sectional study. We will characterize neuroanatomical differences in children and young adults with T1 DM, vs. normal controls. Our center has participated in the Diabetes Research in Children Network (DirecNet), a successful, NIH funded consortium of 5 pediatric diabetes centers and a coordinating center established to study hypoglycemia in children with T1 DM. We have excellent infrastructure, trained personnel, a highly efficient system of patient recruitment, and successful history of efficient protocol completion. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HD041915-07
Application #
7501516
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (20))
Program Officer
Winer, Karen
Project Start
2001-09-30
Project End
2012-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
7
Fiscal Year
2008
Total Cost
$202,371
Indirect Cost
Name
University of Iowa
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Fox, Larry A; Hershey, Tamara; Mauras, Nelly et al. (2018) Persistence of abnormalities in white matter in children with type 1 diabetes. Diabetologia 61:1538-1547
Mazaika, Paul K; Aye, Tandy; Reiss, Allan L et al. (2018) Large Changes in Brain Volume Observed in an Asymptomatic Young Child With Type 1 Diabetes. Diabetes Care 41:1535-1537
Foland-Ross, Lara C; Reiss, Allan L; Mazaika, Paul K et al. (2018) Longitudinal assessment of hippocampus structure in children with type 1 diabetes. Pediatr Diabetes :
Saggar, Manish; Tsalikian, Eva; Mauras, Nelly et al. (2017) Compensatory Hyperconnectivity in Developing Brains of Young Children With Type 1 Diabetes. Diabetes 66:754-762
Mazaika, Paul K; Weinzimer, Stuart A; Mauras, Nelly et al. (2016) Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes 65:476-85
Tansey, M; Beck, R; Ruedy, K et al. (2016) Persistently high glucose levels in young children with type 1 diabetes. Pediatr Diabetes 17:93-100
Hosseini, S M Hadi; Mazaika, Paul; Mauras, Nelly et al. (2016) Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes. Hum Brain Mapp 37:4034-4046
Cato, M Allison; Mauras, Nelly; Mazaika, Paul et al. (2016) Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months. J Int Neuropsychol Soc 22:293-302
Mauras, Nelly; Mazaika, Paul; Buckingham, Bruce et al. (2015) Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia. Diabetes 64:1770-9
Arbelaez, Ana Maria; Xing, Dongyuan; Cryer, Philip E et al. (2014) Blunted glucagon but not epinephrine responses to hypoglycemia occurs in youth with less than 1 yr duration of type 1 diabetes mellitus. Pediatr Diabetes 15:127-34

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