NCT04089332

Insulin Resistance in Adolescents

Insulin Resistance, Cognitive Health, and Perfusion of the Adolescent Brain

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 12 Years – 18 Years
• Healthy volunteers: Accepted

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.

Conditions

• Insulin Resistance

Interventions

Type	Name	Description
OTHER	Oral Glucose Tolerance Test (OGTT)	Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
DEVICE	3 Tesla MRI	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.
DEVICE	Intravenous Catheter	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.
OTHER	Cognitive Tests	A battery of cognitive tests will be completed by the subject.

Timeline

• Start date: 2019-10-04
• Primary completion: 2022-07-31
• Completion: 2022-07-31
• First posted: 2019-09-13
• Last updated: 2024-09-05
• Results posted: 2024-09-05

Locations

1 site across 1 country: United States