Objective We ascertain whether pediatric obesity without clinically-significant insulin resistance (IR) impacts brain structure and function. Design and Methods Thirty obese and 30 matched lean adolescents, all without clinically-significant IR or a diagnosis of metabolic syndrome (MetS), received comprehensive endocrine, neuropsychological, and MRI evaluations. Results Relative to lean adolescents, obese non-IR adolescents had significantly lower academic achievement (i.e. arithmetic and spelling) and tended to score lower on working memory, attention, psychomotor efficiency and mental flexibility. In line with our prior work on adolescent MetS, memory was unaffected in uncomplicated obesity. We also uncovered reductions in the thickness of the orbitofrontal and anterior cingulate cortices as well as reductions of microstructural integrity in major white matter tracts without gross volume changes. Conclusions We document, for the first time, that adolescents with uncomplicated obesity already have subtle brain alterations and lower performance in selective cognitive domains. When interpreting these preliminary data in the context of our prior reports of similar, but more extensive brain findings in obese adolescents with MetS and T2DM, we conclude that “uncomplicated” obesity may also result in subtle brain alterations, suggesting a possible dose effect with more severe metabolic dysregulation giving rise to greater abnormalities.
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