Exercise in Adolescents With Insulin Resistance

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.

Insulin resistance (IR), a hallmark of metabolic syndrome and diabetes, is strongly linked to numerous health disorders, including cardiovascular and cerebrovascular disease. In adults, data indicate IR negatively impacts brain structure and function, such as decreased regional brain volumes, increased white matter hyperintensities, and poorer memory and attention, all of which are hallmarks of Alzheimer's disease and related dementias. In parallel with data from adults, emerging data from adolescents with IR suggest similar brain structural and functional changes. Importantly, these changes occur during a critical period for proper brain development and maturation, thus having a potentially fateful impact on these young brains as they mature into adulthood.

In addition to brain structural and cognitive changes, IR is also associated with lower cerebral blood flow (CBF), which is linked to neurocognitive problems in adults. The consequences of IR on cerebrovascular dysfunction- and its interaction with neurocognition- in adolescents remain largely unexplored. Therefore, impaired vascular function may hold tremendous influence over brain health in adolescents at a vital period in brain development.

Exercise is a key factor in treating IR from a metabolic perspective, and acts as the only effective intervention known to combat dementia-related diseases in adults. Furthermore, exercise can acutely increase cognitive abilities and CBF, and adults with higher aerobic fitness demonstrate greater CBF, and CBF is increased following exercise training. With this as background, a few questions emerge regarding adolescents with IR: is there a dose-response relationship between IR severity and cognitive function? Can exercise improve cognition and impact brain health? What is the role of vascular function in cognition on potential exercise-induced improvements?

The long-term goal of this research program is to determine the influence of IR, physical activity, and their interaction on brain development in adolescents by interrogating the relationships between neurocognition, brain structure, and underlying mechanisms. The primary goal of the current pilot project is to quantify neurocognitive function in relation to the severity of IR and use acute exercise as a tool to improve function. The central hypothesis is that as IR worsens: 1) subtle neurocognitive abnormalities worsen, 2) exercise-mediated improvements in neurocognitive function are blunted, due in part to 3) reduced CBF responses.

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.

Eligibility Criteria:
Inclusion Criteria:

* Age 12-18 years inclusive
* Typically developing and cognitively intact

Exclusion Criteria:

* Diabetes (≥126 mg dL-1 fasting glucose)
* Insulin treatment or sensitizing drugs
* Diagnosis of kidney, pulmonary, or heart disease (an asthma diagnosis that is not currently being treated with a daily controller medicine or asthma that requires medication use prior to exercise is not considered a pulmonary disease)
* Current smoking (defined as use of nicotine \>5 times in the past month)
* Pregnancy
* Neurological or developmental disorders (e.g., intellectual disability, autism)
* Significant head injury or medical conditions (e.g., concussion, encephalopathy, seizure disorder)
* Inability to undergo the MRI procedure
* Weight less than 94.5 lbs (42.9 kg) to adhere to safety guidelines regarding blood sampling and OGTT administration
* Tanner Stage \<3
* Any other circumstance deemed by the PI not addressed above