Type 2 Diabetes, Diabetes Type 2, Diabetic Nephropathies, Nephropathy, Obesity, Adolescent Obesity, Diabetic Kidney Disease
Conditions
Brief summary
The current protocol plans to enroll participants with youth-onset Type 2 Diabetes (T2D) as well as obese and lean controls from the Renal-HEIR - Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study (n=100) \[COMIRB #16-1752\] in a prospective investigation that seeks to 1) define the changes in kidney function by gold standard techniques and energetics by functional Magnetic Resonance Imaging (MRI) in adolescents with and without T2D as they transition to young adulthood; 2) quantify kidney oxidative metabolism by 11C-acetate Positron Emission Tomography (PET) in a subset of participants who are ≥18 years of age with youth-onset T2D and/or obesity; 3) determine peripheral arterial stiffness by SphygmoCor. Mechanistic insight will be provided by transcriptomic analyses of repeat biopsies 3-years after their initial biopsy for eligible participants with youth-onset T2D, as well as molecular analysis of tissue obtained from J-wire endovascular biopsies. This study will also leverage this well-characterized cohort of youths to define youth-onset T2D-related changes in brain morphology and function by structural MRI and resting-state functional MRI and through the assessment of cognitive function (fluid and crystallized intelligence) using the NIH Toolbox Cognitive Battery (NIHTB-CB), as an exploratory objective. All enrollees in Renal-HEIR have consented to be contacted for future research opportunities.
Interventions
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
DRUGDextran 40
Diagnostic aid/agent used to measure glomerular size selectivity
PROCEDURERenal Biopsy
Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.
RADIATIONPositron Emission Tomography
Imaging study performed to study renal oxidative metabolism
Sponsors
University of Colorado, Denver
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to 26 Years
Inclusion criteria
* Obese youth with and without Type 2 Diabetes + lean controls who were previously enrolled in the Renal HEIR Study * Participants who will undergo a PET Scan: ≥ 18 years
Exclusion criteria
* Anemia * Seafood, iodine, or penicillin allergy * Pregnancy * MRI Scanning contraindications (claustrophobia, implantable devices, \>550 lbs) * History of bleeding or clotting disorders, thrombocytopenia, warfarin and/or heparin use * Taking sulfonamides, procaine, thiazolsulfone or probenecid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Arteriosclerosis | 1 Hour | Measured by Renal Biopsy |
| Renal Oxidative Metabolism | 1 Hour | Measured by PET Scan |
| Blood Volume Fraction | 1 Hour | Measured by PET Scan |
| Glomerular Basement Membrane Width | 1 Hour | Measured by Renal Biopsy |
| Mesangial Expansion | 1 Hour | Measured by Renal Biopsy |
| Interstitial Fibrosis | 1 Hour | Measured by Renal Biopsy |
| Spatial Transcriptomics | 1 Hour | Measured by Renal Biopsy |
| Spatial Metabolomics | 1 Hour | Measured by Renal Biopsy |
| Effective Renal Plasma Flow (ERPF) | 4 Hours | Measured by PAH clearance |
| Glomerular Filtration Rate | 4 Hours | Measured by Iohexol Clearance |
| Glomerular Size Selectivity | 4 hours | Measured by Dextran sieving |
| Renal Oxygen Availability | 1 hour | Measured by functional kidney MRI |
| Renal Perfusion | 1 hour | Measured by functional kidney MRI + PET Scan |
| 11-C Acetate Tracer Uptake | 1 Hour | Measured by PET Scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whole brain gray matter volume | 1 Hour | Measured by brain MRI |
| Whole brain cortical thickness | 1 Hour | Measured by brain MRI |
| Whole brain resting-state network connectivity | 1 Hour | Measured by brain MRI |
| Age-corrected composite fluid cognition score | 1 Hour | Measured by brain MRI |
| Pulse Wave Velocity between Carotid and Femoral Artery | 10 minutes | Measured by PWV |
Countries
United States
Outcome results
None listed