Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress (PANTHER Study)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Aminohippurate Sodium Inj 20%, Iohexol Inj 300 MG/ML, Dextran 40.
- Who it may be relevant to
- Registry conditions: Type 2 Diabetes Mellitus, Diabetic Kidney Disease, Adolescent Obesity, Pre Diabetes. Basic parameters: 8 years — 14 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
PANTHER Study: Puberty, Diabetes, and the Kidneys, When Eustress Becomes Distress
Overview
Early diabetic kidney disease (DKD) occurs in 50-70% of youth with type 2 diabetes (T2D) and confers high lifetime risk of dialysis and premature death. Youth-onset T2D typically manifests during or shortly after puberty in adolescents with obesity. Epidemiological data implicate puberty as an accelerator of kidney disease in youth with obesity and diabetes and the investigators posit that the link between puberty and T2D-onset may explain the high burden of DKD in youth-onset T2D. A better understanding of the impact of puberty on kidney health is needed to promote preservation of native kidney function, especially in youth with T2D.
Detailed description
Puberty is a complex process of physiological changes, including neuroreproductive and growth hormone activation and rapid organ growth, that may predispose organs to injury. The kidneys may be especially susceptible because they are highly metabolically active and second only to the heart with respect to oxygen consumption per tissue mass. During puberty, the kidneys almost double in size, likely increasing the kidneys' already high energy expenditure. In parallel, puberty is associated with physiologic insulin resistance (IR), which is accentuated in obesity. Our central hypothesis is that obese youth with prediabetes and T2D experience relative kidney hypoxia during puberty due to a metabolic mismatch between increased energy expenditure and impaired substrate metabolism. In turn, the kidney hypoxia results in loss of glomerular charge and size selectivity leading to increased transglomerular transport of protein and kidney dysfunction. Our preliminary data showed that pubertal adolescents with obesity and/or diabetes exhibit relative kidney hypoxia compared to normal weight controls using functional magnetic resonance imaging (MRI) and that relative kidney hypoxia is greater in late vs. early puberty. However, determining the pubertal mechanisms contributing to kidney injury in youth with obesity and T2D requires serial evaluations throughout puberty. To assess the impact of pubertal changes within a 5-year study period, the investigators propose an accelerated longitudinal study design in which the investigators will enroll adolescents (8-14 years, 50% girls) with obesity and/or elevated hemoglobin A1c (HbA1c ≥6%) \[n=60\], and healthy normoglycemic controls \[n=40\] at Tanner (pubertal) stages 1-4 and examine them at baseline, 1 and 2-years. The investigators will then compare data by Tanner stage to construct an integrated portrayal of the physiological changes that occur throughout puberty. Given the rarity of T2D prior to pubertal onset, the investigators chose to enroll a high high-risk group: youth with obesity and/or HbA1c ≥6.0% to represent youth ranging from those at magnified risk of developing T2D to those recently diagnosed.
Interventions
- Drug Aminohippurate Sodium Inj 20%
Diagnostic aid/agent used to measure effective renal plasma flow (ERPF) - Drug Iohexol Inj 300 MG/ML
Diagnostic aid/agent used to measure glomerular filtration rate (GFR) - Drug Dextran 40
Diagnostic aid/agent used to measure glomerular size and selectivity
Primary outcome measures
- Effective renal plasma flow (ERPF) [Time frame: 3 Hours]
- Glomerular Filtration Rate (GFR) [Time frame: 3 hours]
Secondary outcome measures (3)
- Insulin Sensitivity [Time frame: 3 hours]
- Renal perfusion [Time frame: 10 min]
- Renal oxygenation [Time frame: 60 min]
Eligibility criteria
Inclusion criteria
- HbA1c ≥6.0% for untreated high-risk group
- BMI ≥ 85th %ile for high-risk group
- Normal HbA1c ≤5.6% for control group
- Type 1 diabetes (T1D) Antibody negative
Exclusion criteria
- History of Chronic kidney disease (CKD) or acute kidney injury (AKI)
- Metabolic disorder prohibiting safe fasting
- Iodine or penicillin allergy
- Pregnancy
- Thrombophilia
- MRI contraindications
- Hormone therapy
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
United States · 2 centers
- Children's Hospital Colorado — Aurora
- Seattle Children's Hospital — Seattle
Identifiers
NCT: NCT05008276 · 21-3019