Copeptin in Adolescent Participants With Type 1 Diabetes and Early Renal Hemodynamic Function

• Status: Completed
• Trial end date: 2021-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Over 1.25 million Americans have type 1 diabetes (T1D), increasing risk for early death from cardiorenal disease. The strongest risk factor for cardiovascular disease (CVD) and mortality in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protect against DKD.

Hyperfiltration is common in youth with T1D, and predicts progressive DKD. Hyperfiltration is also associated with early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Intrarenal hemodynamic function is strongly influenced by the renin-angiotensin-aldosterone system (RAAS), which is also considered a key player in the pathogenesis of DKD. Preliminary data demonstrate differences in intrarenal hemodynamic function and RAAS activation in early and advanced DKD in T1D. However, the pathophysiology contributing to the differences observed in RAAS activation and intrarenal hemodynamic function in T1D are poorly defined Animal research demonstrates that arginine vasopressin (AVP) acts directly to modify intrarenal hemodynamic function, but also indirectly by activating RAAS. Preliminary data suggest that elevated copeptin, a marker of AVP, which predicts DKD in T1D adults, independently of other risk factors. However, no human studies to date have examined how copeptin relates to intrarenal hemodynamic function in early DKD in T1D. A better understanding of this relationship is critical to inform development of new therapies targeting the AVP system in T1D. Accordingly, in this study, the investigators propose to define the relationship between copeptin and intrarenal hemodynamics in early stages of DKD, by studying copeptin levels, renal plasma flow, and glomerular filtration in youth (n=50) aged 12-21 y with T1D duration < 10 y.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado Denver School of Medicine Barbara Davis Center

Criteria

Inclusion Criteria:

• Antibody+ T1D with <10 yr duration

• Age 12-21 years

• BMI ≥ 5%ile

• Weight<350 lbs and > 57 lbs.

• No anemia

• HbA1c <12%

Exclusion Criteria:

• Severe illness, recent diabetic ketoacidosis (DKA)

• Estimated Glomerular Filtration Rate (eGFR) <60ml/min/1.73m2 or creatinine > 1.5mg/dl or history of ACR≥300mg/g

• Anemia or allergy to shellfish or iodine

• Pregnancy or nursing

• MRI scanning contraindications (claustrophobia, implantable devices, >350 lbs)

• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, procaine, thiazolsulfone or probenecid, atypical antipsychotics and steroids