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

Manish Saggar, Eva Tsalikian, Nelly Mauras, Paul Mazaika, Neil H. White, Stuart Weinzimer, Bruce Buckingham, Tamara Hershey, Allan L. Reiss
2016 Diabetes  
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
more » ... ntrol subjects without diabetes (n = 26; mean age = 7.43 years; 14 females). Using both model-driven seedbased 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. Young children with type 1 diabetes (T1D) are particularly susceptible to extreme swings of hyper-and hypoglycemia (dysglycemia) due to their underlying sensitivity to insulin, unpredictable eating and exercise patterns, and inability to reliably communicate signs or symptoms of hypoglycemia. As the brain is reliant on glucose for metabolism, the effect of dysglycemia on brain development and functioning is an area of physiological and clinical interest (1). Several previous studies have found that individuals diagnosed with T1D at a younger age (;4 years) may be at a greater risk for developing neuropsychological deficits at later ages (2-4). Accordingly, better understanding of how dysglycemia can affect brain anatomy and connectivity in very young children might allow clinicians to better identify patients at greatest risk for developing cognitive alterations in the future. Successfully maintaining control of blood glucose levels requires an effective alliance between interoceptive sensing of changing glycemic levels as well as complex behavioral management strategies by the individual that include awareness of dysglycemic symptoms, motivation, food/ fluid intake, etc. (1). Thus, different brain functional units must coordinate as networks to mediate the cognitive and behavioral aspects associated with dysglycemia (1). However, very little is known about the deleterious effects of T1D on this network-level coordinated functioning across brain regions in young children. Two studies have previously used resting-state functional MRI (rsfMRI) to examine differences in intrinsic (or at-rest) connectivity among brain regions in adults with T1D as
doi:10.2337/db16-0414 pmid:27702833 pmcid:PMC5319714 fatcat:trdjxvkqijhxzfodvoygcuw244