With the explosion of obesity among the young, T2DM is no longer rare among adolescents. It is important to better understand the effects of T2DM on the brain of adolescents, particularly at a time when their ability to learn and do well in school will greatly impact their future. The objective of this pilot study is to carefully characterize the nature of the cognitive impairments that are likely present among obese adolescents with T2DM and to use an MRI-based approach to explore the possible brain substrates underlying those deficits. We have pilot data showing cognitive problems in adolescents with T2DM and preliminary data suggesting that there may be abnormalities in white matter integrity associated with diabetes, thus justifying these studies. Utilizing a case-control design, we will study two groups of 25 obese children each, predominantly ethnic minority, between 16 and 19 years of age, and 65% female. In general the children with T2DM will have been diagnosed for 1-4 years. Controls will have normal glucose tolerance and no significant insulin resistance (IR) and be matched 1:1 for obesity, age, ethnicity (race), and gender to those with T2DM. We will utilize a carefully selected, broad-based, and relatively brief battery of well-standardized neuropsychological tests with age and education norms. In addition, the MRI brain evaluation will use well-established procedures. We have considerable experience with all the evaluations proposed in this study. The proposed work will provide the key preliminary data to justify a more comprehensive assessment of the brain in metabolic disorders associated with obesity in childhood. This improved understanding may suggest that the brain be formally evaluated as a site of potential complications in diabetes and provide the data needed to design more aggressive prevention and intervention programs aimed at improving brain function among the young. ? ?
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