Insulin Resistance
Conditions
Brief 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.
Interventions
OTHEROral Glucose Tolerance Test (OGTT)
Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
DEVICE3 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.
DEVICEIntravenous 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.
OTHERCognitive Tests
A battery of cognitive tests will be completed by the subject.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
Yes
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | data collected at baseline visit (HOMA-IR) and one other study visit (Cognitive Function Tests) (up to 4 hours total time of data collection over two visits - data collection not temporally dependent) | HOMA-IR was measured from each participant at baseline (up to 1 hour visit) and a battery of cognitive instruments (listed here) were measured at a different study visit (2-3 hours of time). A relationship between individual HOMA-IR and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared). |
| Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min) | 1 study visit, measured at baseline and peak insulin (45-60 minutes after baseline) | CBF will be measured via MRI before OGTT (baseline) and after OGTT at Peak insulin. |
| Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | data collected at baseline (CBF - up to 1 hour) and Cognitive Function data collected at another study visit (up to 3 hours), data collection over 2 study visits up to 4 hours total, data collection not temporally dependent | Cerebral Blood Flow was measured from each participant at baseline (without OGTT MRI Visit) and a battery of cognitive instruments (those listed below) were measured at a different study visit. A relationship between individual Cerebral Blood Flow and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared). |
| Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | through study completion (up to 2 years) | Mediation analysis is a statistical method used to explain the influence of an outside variable (mediator) that may modify the direct relationship between the Independent (X) and Dependent variable (Y). (X - Mediator - Y) Mediation analysis was used to explore the impact of cerebral blood flow on the relationship between HOMA-IR and cognitive function. This analysis was conducted on 11 separate cognitive function tests, looking at verbal skills, memory, executive function, and self-reported quality of life rating. In the first set of analyses, the mediator was grey matter baseline, which is the cerebral blood flow in the resting state. The second set of analyses, the mediator was grey matter change with OGTT, which is the cerebral blood flow changing from rest to response from Oral Glucose Tolerance Test (OGTT). Positive/negative effect numbers indicated that the total effect of the relationship was positive/negative. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from October 2019 to April 2022. Participants were 12-18 years old during Covid-19 pandemic, and thus had very delayed access to vaccines, limiting enrollment. Pandemic related safety issues effected study conduct. Not all enrolled participants completed all (up to 5, 3 for the primary aims) study visits as a result. Because the data collected in each visit was not dependent on the other visit in a temporal manner, the study visits could occur in any order.
Pre-assignment details
34 participants were consented, but due to the Covid-19 pandemic, only 23 participants started the study (completed at least 1 study visit).
Participants by arm
| Arm | Count |
|---|---|
| Enrolled, Eligible Oral Glucose Tolerance Test: Eligible subjects will undergo MRI scanning before and after oral glucose tolerance test.
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.
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.
Cognitive Tests: A battery of cognitive tests will be completed by the subject. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Completed only OGTT, no analysis possible | 1 |
| Overall Study | COVID-19 Pandemic safety issues | 6 |
| Overall Study | Moved in the MRI, no analysis possible | 1 |
Baseline characteristics
| Characteristic | Enrolled, Eligible |
|---|---|
| Age, Continuous | 14.53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 2 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min)
CBF will be measured via MRI before OGTT (baseline) and after OGTT at Peak insulin.
Time frame: 1 study visit, measured at baseline and peak insulin (45-60 minutes after baseline)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Enrolled, Eligible | Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min) | Perfusion of Gray Matter at Baseline | 64.25666 mL/100g/min | Standard Deviation 11.24309 |
| Enrolled, Eligible | Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min) | Perfusion of Gray Matter at Peak Insulin (Avg. 45 min) | 66.96387836 mL/100g/min | Standard Deviation 13.93884706 |
| Enrolled, Eligible | Change in Cerebral Blood Flow (CBF) as Determined by MRI (mL/100g/Min) | Change in Perfusion of Gray Matter | 2.707215114 mL/100g/min | Standard Deviation 5.642163965 |
Comparison: Change in Gray Matter Perfusion vs. HOMA-IRp-value: 0.558Regression, Linear
Comparison: Baseline Gray Matter vs. HOMA-IRp-value: 0.057Regression, Linear
Primary
Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared)
Cerebral Blood Flow was measured from each participant at baseline (without OGTT MRI Visit) and a battery of cognitive instruments (those listed below) were measured at a different study visit. A relationship between individual Cerebral Blood Flow and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared).
Time frame: data collected at baseline (CBF - up to 1 hour) and Cognitive Function data collected at another study visit (up to 3 hours), data collection over 2 study visits up to 4 hours total, data collection not temporally dependent
Population: This includes all the participants that completed the cognitive visit of the study. Because data collected in each visit was not dependent on other visits in a temporal manner, study visits occurred in any order.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | WRAML (Picture Memory) A general memory measure of picture recognition | 0.185 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities. | 0.132 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning | 0.119 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | NIH Toolbox (List Learning) A cognitive measure of working memory | 0.06 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols) | 0.0593 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure | 0.366 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli) | 0.000497 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory | 0.0688 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | D-KEFS (Color-Word Interference) A measure of cognitive flexibility through inhibition | 0.234 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | D-KEFS (Trail Making Test) A measure of mental flexibility (motor speed) | 0.00466 R-squared |
| Enrolled, Eligible | Linear Relationship Between Cerebral Blood Flow and Cognitive Function (R-squared) | PedsQL (Child 8-12 / Teen 13-18) A measure of health-related quality of life (HRQOL) in children | 0.0344 R-squared |
Comparison: WASI II (Verbal IQ) vs. Cerebral Blood Flowp-value: 0.377Regression, Linear
Comparison: WASI II (Performance IQ) vs. Cerebral Blood Flowp-value: 0.402Regression, Linear
Comparison: NIH Toolbox (Flanker Inhibitory Control and Attention) vs. Cerebral Blood Flowp-value: 0.203Regression, Linear
Comparison: NIH Toolbox (Pattern Comparison) vs. Cerebral Blood Flowp-value: 0.967Regression, Linear
Comparison: NIH Toolbox (Picture Sequence) vs. Cerebral Blood Flowp-value: 0.616Regression, Linear
Comparison: WRAML (Picture Memory) vs. Cerebral Blood Flowp-value: 0.287Regression, Linear
Comparison: D-KEFS (Color-Word Interference) vs. Cerebral Blood Flowp-value: 0.225Regression, Linear
Comparison: D-KEFS (Trail Making Test) vs. Cerebral Blood Flowp-value: 0.872Regression, Linear
Comparison: PedsQL (Child 8-12 / Teen 13-18) vs. Cerebral Blood Flowp-value: 0.66Regression, Linear
Primary
Linear Relationship Between HOMA-IR and Cognitive Function (R-squared)
HOMA-IR was measured from each participant at baseline (up to 1 hour visit) and a battery of cognitive instruments (listed here) were measured at a different study visit (2-3 hours of time). A relationship between individual HOMA-IR and Cognitive Function was hypothesized and a measured via Linear Regression (R-squared).
Time frame: data collected at baseline visit (HOMA-IR) and one other study visit (Cognitive Function Tests) (up to 4 hours total time of data collection over two visits - data collection not temporally dependent)
Population: This includes all the participants that completed the cognitive visit of the study. Because data collected in each visit was not dependent on other visits in a temporal manner, study visits occurred in any order.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | D-KEFS (Color Word Interference) A measure of cognitive flexibility through inhibition | 0.000224 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | WASI II (Verbal IQ) Measure of intellectual ability, sub-tests Vocabulary and Similarities | 0.205 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | WASI II (Performance IQ) Measure of intellectual ability, sub-tests Block Design, Matrix Reasoning | 0.299 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | NIH Toolbox (List Learning) A cognitive measure of working memory | 0.738 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | NIH Toolbox (Oral Symbol Digit Test) A cognitive measure of processing speed (numbers/symbols) | 0.0264 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | NIH Toolbox (Flanker Inhibitory Control and Attention) Executive function measure | 0.186 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | NIH Toolbox (Pattern Comparison) A cognitive measure of processing speed (stimuli) | 0.04 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | NIH Toolbox (Picture Sequence) A cognitive measure of episodic memory | 0.47 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | WRAML (Picture Memory) A general memory measure of picture recognition | 0.0572 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | D-KEFS (Trail Making Test) A measure of mental flexibility (motor speed) | 0.392 R-squared |
| Enrolled, Eligible | Linear Relationship Between HOMA-IR and Cognitive Function (R-squared) | Peds QL (Child 8-12 / Teen 13-18) A measure of health-related quality of life (HRQOL) in children | 0.481 R-squared |
Comparison: WASI II (Verbal IQ) vs HOMA-IRp-value: 0.162Regression, Linear
Comparison: WASI II (Performance IQ) vs HOMA-IRp-value: 0.082Regression, Linear
Comparison: NIH Toolbox (Flanker Inhibitory Control and Attention) vs HOMA-IRp-value: 0.286Regression, Linear
Comparison: NIH Toolbox (Pattern Comparison) vs HOMA-IRp-value: 0.635Regression, Linear
Comparison: NIH Toolbox (Picture Sequence) vs HOMA-IRp-value: 0.061Regression, Linear
Comparison: WRAML (Picture Memory) vs. HOMA-IRp-value: 0.479Regression, Linear
Comparison: D-KEFS (Color-Word Interference) vs. HOMA-IRp-value: 0.965Regression, Linear
Comparison: D-KEFS (Trail Making Test) vs. HOMA-IRp-value: 0.039Regression, Linear
Comparison: PedsQL (Child 8-12 / Teen 13-18) vs. HOMA-IRp-value: 0.018Regression, Linear
Primary
Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function
Mediation analysis is a statistical method used to explain the influence of an outside variable (mediator) that may modify the direct relationship between the Independent (X) and Dependent variable (Y). (X - Mediator - Y) Mediation analysis was used to explore the impact of cerebral blood flow on the relationship between HOMA-IR and cognitive function. This analysis was conducted on 11 separate cognitive function tests, looking at verbal skills, memory, executive function, and self-reported quality of life rating. In the first set of analyses, the mediator was grey matter baseline, which is the cerebral blood flow in the resting state. The second set of analyses, the mediator was grey matter change with OGTT, which is the cerebral blood flow changing from rest to response from Oral Glucose Tolerance Test (OGTT). Positive/negative effect numbers indicated that the total effect of the relationship was positive/negative.
Time frame: through study completion (up to 2 years)
Population: Mediation analysis was conducted on a limited data set due to the low number of participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Verbal List Learning (Grey Matter Baseline) | 0.5834 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WASii- Verbal (Grey Matter Change with OGTT) | -0.9125 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WASii- Verbal (Grey Matter Baseline) | 1.6787 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WASii-Performance (grey Matter Baseline) | -3.3431 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WRAML (Grey Matter Baseline) | -0.8194 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs DKEFS Trail Making (Grey Matter Baseline) | -0.1702 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs DKEFS Inhibition Stroop (Grey Matter Baseline) | -0.2095 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs PEDS QL Child Report (Grey Matter Baseline) | 30.7925 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Oral Digit Symbol (Grey Matter Baseline) | 6.98 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Flanker (Grey Matter Baseline) | 1.0747 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Pattern Comparison (Grey Matter Baseline) | 2.3718 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Picture Memory (Grey Matter Baseline) | -0.9954 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WASii-Performance (grey Matter Change with OGTT) | -2.8222 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs WRAML (Grey Matter Change with OGTT) | -0.0008 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs DKEFS Trail Making (Grey Matter Change with OGTT) | 0.1719 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs DKEFS Inhibition Stroop (Grey Matter Change with OGTT) | -0.3754 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs PEDS QL Child Report (Grey Matter Change with OGTT) | -7.4081 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Verbal List Learning (Grey Matter Change with OGTT) | 0.2067 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Oral Digit Symbol (Grey Matter Change with OGTT) | -2.1898 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Flanker (Grey Matter Change with OGTT) | -2.8883 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Pattern Comparison (Grey Matter Change with OGTT) | 0.5842 beta value |
| Enrolled, Eligible | Mediation Analysis of the Indirect Effect of Cerebral Blood Flow on Insulin Resistance and Cognitive Function | HOMA-IR vs NIH Toolbox Picture Memory (Grey Matter Change with OGTT) | -1.5724 beta value |