Youth-Onset Type 2 Diabetes and Heart Disease: The Young at Heart Prospective Cohort Study
- Conditions
- ObesityType 2 Diabetes
- Registration Number
- NCT06730113
- Brief Summary
Background:
Type 2 diabetes is a disease that affects blood sugar levels. Complications can include heart and blood vessel (vascular) diseases. Rates of type 2 diabetes have tripled in children and young adults over the last 40 years. Vascular diseases are also increasing in young people.
Objective:
To learn more about factors, including type 2 diabetes, that may cause vascular disease in young people.
Eligibility:
People aged 12 to 25 years who (1) have type 2 diabetes; (2) are overweight but not diabetic; (3) or are lean and healthy. Biological parents are also needed.
Design:
Young participants will visit the NIH clinic once a year for up to 25 years. Each visit will take 4 days. Before each visit, participants will wear devices to track their sleep, activity, and blood sugar levels for 7 to 10 days.
At each visit, participants will have tests including:
Samples: They will provide blood, urine, and stool samples.
Heart: They will ride a stationary bike for 6 minutes with stickers applied to their chest.
Scans: They will lie on a bed that slides into a tube; the machine will take pictures of the inside of their body.
Energy: They will wear a hood over their head to measure the air they breathe.
Social stress: They will give a speech for 10 minutes to show their body s response to stress.
Glucose: They will drink a sweet drink to see how their blood sugar changes.
Biological parents will have 1 study visit. They will have blood tests. They will fill in questionnaires about their lifestyle and stress.
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- Detailed Description
Study Description:
This study will evaluate the pathophysiological features of cardiovascular disease in youth-onset type 2 diabetes (Y-T2DM) using a multi-level, multi-domain approach of socio-ecological risk factors (societal, community, and individual). We will employ a prospective, observational study design in youth aged 12-25 years to compare Y-T2DM with age and BMI-matched youth with overweight or obesity (Y-OW) and age-matched healthy lean peers (Y-Lean). The study will also include a single-day visit for biological parents of enrolled Y-T2DM, Y-OW and Y- lean, to assess parental factors involved in the pathophysiology of cardiovascular disease in Y-T2DM.
Objectives:
Primary Objectives:
* To compare pulse wave velocity (PWV) at baseline in Y-T2DM vs Y-OW and age-matched peers Y-Lean.
* To compare augmentation index (Aix) at baseline in Y-T2DM vs Y-OW and age-matched peers Y-Lean.
* To compare pulse wave velocity (PWV) at 5 years in Y-T2DM vs Y-OW and age-matched peers Y-Lean.
* To compare augmentation index (Aix) at 5 years in Y-T2DM vs Y-OW and age-matched peers Y-Lean.
Secondary Objectives:
In Y-T2DM vs. Y-OW vs. Y-Lean youth,
* To evaluate coronary artery structure and endothelial function at baseline and 5 years.
* To evaluate the relationship of pulse wave velocity and coronary artery structure \& endothelial function with atherogenic and remnant lipoproteins.
Exploratory Objectives:
In Y-T2DM vs. Y-OW vs. Y-Lean youth,
* To evaluate annual change in vascular aging (measured by the change in pulse wave velocity and endothelial function).
* To evaluate the relationship of physiologic, psychological stress (measured with the allostatic load score, ALS), psychosocial and behavioral factors with vascular aging.
* To evaluate biomarkers for vascular aging; ex. Beta-cell function, insulin resistance, inflammatory markers, and novel lipid parameters.
* To evaluate the association of polygenic risk scores (PRS) in Y-T2DM and with changes in glucose and metabolic profiles (e.g., triglycerides) over time.
* To evaluate differences in epigenetic aging in youth and parents.
* To determine the prevalence rates of major adverse cardiovascular events (MACE)
Endpoints:
Primary Endpoint:
* Carotid-femoral pulse wave velocity (PWV) at baseline
* Pulse augmentation index (Aix) at baseline
* Carotid-femoral PWV at 5 years
* Pulse Aix at 5 years
Secondary Endpoints:
* Right coronary wall thickness measured by cardiac MRI
* Endothelial function measured by MRI isometric handgrip exercise
* Fasting and postprandial lipoprotein profile (mixed meal test)
Exploratory Endpoints:
Markers of vascular aging (annual change):
* PWV
* Aix
* Endothelial function measured by reactive hyperemia index
* Right coronary wall thickness measured by MRI
* Heart rate variability
* Central Retinal Artery Equivalent
Markers of physiological stress
* Allostatic load score
* Cortisol (serum)
* C-reactive protein and immune biomarkers
Assessment of metabolic variables
* Sigma and insulin sensitivity index (standard 75g OGTT)
* Postprandial lipoproteins (mixed meal test)
* Metabolomics, Lipidomics, Proteomics Measures
* Liver fat and function
* Body composition
Psychosocial, Neighborhood, and individual variables
* Psychosocial Assessments: Binge Eating Disorder Screener-7 (BED-7), Brief Resilience Scale, Diabetes Distress Scale (DDS-17), Emotional Eating Scale, Michigan Neuropathy Screening Instrument (MNSI), PROMIS Emotional Distress - Anxiety, PROMIS Emotional Distress - Depression, PROMIS - Sleep Disturbance, Reward-Based Eating Drive Scale (REDS), Self-assessment of Worries, Concerns, and Burdens Related to Diabetes and Preparation for Transitioning, Substance Use, and Trier social stress task
* Neighborhood Assessments: Adverse Childhood Experience (ACE), Confusion, Hubbub, and Order Scale (CHAOS), MacArthur Scale of Subjective Social Status, Neighborhood Disadvantage Scale, Pediatric ACES and Related Life Events Screening (PEARLS), Unpredictability Beliefs Scale, and U.S. Household Food Insecurity Module.
* Individual Assessments: dietary, activity, sleep assessment questionnaire, stress-related eating, 7-10-day accelerometer (activity, sleep), 7-10-day continuous glucose monitor
Genetic/ Epigenetic
* Genome-wide genotyping array
* Genome-wide DNA methylation array
Five-point MACE
* Acute myocardial infarction
* Stroke
* Cardiovascular mortality
* Hospitalization for unstable angina or revascularization procedures
* Heart failure
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 930
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pulse wave velocity (PWV) 5 Years Carotid-femoral pulse wave velocity (m/s) measured with SphygmaCor
Augmentation index (Aix) 5 Years Augmentation index (%) measured with SphygmaCor
- Secondary Outcome Measures
Name Time Method Right coronary wall thickness 5 years During cardiac MRI, cross-sectional analysis of right coronary artery vessel wall thickness; greater thickness associated with increased risk for endothelial dysfunction
Endothelial Function 5 years During cardiac MRI, measurements of change in vessel wall thickness during isometric handgrip exercise. Smaller change associated with endothelial dysfunction
Fasting remnant lipoproteins Baseline Fasting plasma remnant lipoproteins measured with nuclear magnetic spectroscopy; higher concentrations associated with increased cardiovascular disease risk
Postprandial remnant lipoproteins 5 years Plasma remnant lipoproteins measured with nuclear magnetic spectroscopy. Incremental area under the curve for plasma remnant lipoproteins will be calculated from the standard 5-hour mixed meal tolerance test.
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Trial Locations
- Locations (2)
Children's National Hospital (CNH)
🇺🇸Washington, District of Columbia, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States