Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes

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. Early DKD is
characterized by changes in intrarenal hemodynamic function, including increased renal plasma
flow (RPF) and glomerular pressure with resultant hyperfiltration, is common in Y-T2D, and
predicts progressive DKD.

Studies evaluating the two currently approved medications for treating T2D in youth
(metformin and insulin) have shown these medications are not able to improve β-cell function
over time in the youth. However, recent evidence suggests that bariatric surgery in adults is
associated with improvements in diabetes outcomes, and even T2D remission in many patients.
Limited data in youth also supports the benefits of bariatric surgery, regarding weight loss,
glycemic control in T2D, and cardio-renal health. While weight loss is important, the acute
effect of bariatric surgery on factors such as insulin resistance likely includes weight
loss-independent mechanisms. A better understanding of the effects of bariatric surgery on
pancreatic function, intrarenal hemodynamics, renal O2 and cardiovascular function is
critical to help define mechanisms of surgical benefits, to help identify potential novel
future non-surgical approaches to prevent pancreatic failure, DKD and cardiovascular disease.

The investigators' overarching hypotheses are that: 1) Y-T2D is associated with IR,
pancreatic dysfunction, intrarenal hemodynamic dysfunction, elevated renal O2 consumption and
cardiovascular dysfunction which improve with bariatric surgery, 2) The early effect of
bariatric surgery on intrarenal hemodynamics is mediated by improvement in IR and weight
loss. To address these hypotheses, the investigators will measure GFR, RPF, glomerular
pressure and renal O2, in addition to aortic stiffness, β-cell function and insulin
sensitivity in youth ages 12-21 with T2D (n=15) before and after vertical sleeve gastrectomy
(VSG).