Renal HEIR Study: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study

Type 2 diabetes (T2D) in youth is increasing in prevalence in parallel with the obesity
epidemic. In the US, almost half of patients with renal failure have DKD, and ≥80% have T2D.
Compared to adult-onset T2D, youth with T2D have a more aggressive phenotype with greater
insulin resistance (IR), more rapid β-cell decline and higher prevalence of diabetic kidney
disease (DKD), arguing for separate and dedicated studies in youth-onset T2D. Hyperfiltration
is common in youth with T2D, and predicts progressive DKD. Hyperfiltration may also be
associated with early changes in intrarenal hemodynamic function, including increased renal
plasma flow (RPF) and glomerular pressure. Despite the high prevalence and gravity of DKD in
youth-onset T2D, widely effective therapeutic options are lacking. The investigators'
preliminary data support a strong association between IR and hyperfiltration in youth-onset
T2D, but the pathology contributing to this relationship remains unclear. A better
understanding of the pathophysiology underlying hyperfiltration and its relationship with IR
is critical to inform development of new therapeutics. The investigators' overarching
hypotheses are that: 1) hyperfiltration in youth-onset T2D is associated with changes in
intrarenal hemodynamics, resulting in increased renal oxygen demand, 2) the demand is unmet
by the inefficient fuel profile associated with IR (decreased glucose oxidation and increase
free fatty acid [FFA] oxidation), resulting in renal hypoxia and ultimately renal damage. To
address these hypotheses, the investigators will measure peripheral insulin sensitivity,
adipose insulin sensitivity (FFA suppression), glomerular filtration rate (GFR), RPF, and
renal oxygenation in youth with T2D (n=30), obesity (n=20) and in lean (n=20) controls.