Insulin Resistance in Adolescents
Condition: Insulin Resistance
MeSH terms: Insulin Resistance
Study type: Interventional

Summary: 
      The growing population of adolescents with insulin resistance (IR) is predicted to create a
      large public health burden in the next few decades. This study examines the function of brain
      blood vessels and cognitive function, to test if increasing severity of IR in adolescents is
      related to reduced cognitive function and reduced brain blood vessel function. Findings from
      this study may help create treatments to delay or prevent some of the negative effects of IR
      on cognitive and vascular health.
    

Detailed description: 
      One in five American adolescents is obese. Up to half of those are already exhibiting insulin
      resistance (IR), a hallmark of metabolic syndrome and diabetes linked to serious
      life-altering health disorders, including cardiovascular and cerebrovascular disease. In
      adults, IR negatively affects brain structure and function and is reflected in lower regional
      brain volumes, perfusion, increased white matter hyperintensities and abnormal
      neuropsychological status, especially affecting memory and attention-all changes associated
      with accelerated cognitive and brain aging and increased risk of dementia. In an analogous
      fashion, a limited set of literature suggests adolescents with IR exhibit similar brain
      changes during maturation. The investigators hypothesize that the brains of obese adolescents
      are more susceptible to insults of IR during rapid brain development, positioning them on an
      abnormal cognitive trajectory, and predisposing them to issues related to learning,
      behavioral stress responses, and depression.

      While the metabolic consequences of IR are well described in adolescence, the impact of IR on
      their neurocognitive status (intelligence, memory, attention, executive function, processing
      speed) and cerebrovascular function and their interactions remains largely unexplored. This
      is important since in addition to its classic role as a metabolic hormone, insulin acts as a
      vasodilator and supports neurotrophic signaling in healthy humans. Therefore, dysfunctional
      insulin signaling may hold tremendous influence over brain health in adolescents during this
      vital period of brain development. New insight is required to understand where, when, and how
      IR negatively transforms brain health, including whether a dose-response exists between IR
      severity and anomalies in brain and cognition.

      The long-term goal of this research program is to determine the influence of IR on brain
      development in adolescents through the relationships between neurocognition and cerebral
      blood supply. The primary goal of the current project is to quantify fundamental
      neurocognitive and cerebrovascular function in relation to the severity of IR. The central
      hypothesis is that as IR worsens: a) subtle but meaningful neurocognitive declines emerge; b)
      regional brain perfusion is reduced primarily in areas linked to learning and memory despite
      preserved resting global cerebral blood flow (CBF); c) acute insulin surges exacerbate
      regional hypoperfusion, and d) cognitive scores will be lower, mediated in part by
      insulin-stimulated hypoperfusion.

      Participants will be recruited primarily from pediatric and pediatric endocrinology clinics
      via our collaborator, Dr. Aaron Carrel, and his staff in UWHC Pediatric Endocrinology.
      Additionally, participants will be recruited from the greater Madison, WI community.
    

Intervention name(s): Oral Glucose Tolerance Test; 3 Tesla MRI; Intravenous Catheter; Cognitive Tests
Intervention type(s): Other; Device; Device; Other
Intervention description(s): Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.; A 3 Tesla MRI will be used to assess brain structure, quantify cerebral blood flow and capture cerebral vessel structure at designated time points throughout the study visits.; A blood sampling IV catheter will be used to draw blood samples at specific time points throughout each study visit to measure concentrations of glucose and insulin.; A battery of cognitive tests will be completed by the subject.
Other intervention name(s): OGTT; MRI; Cath
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science