Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)
Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.
• Age ≥ 18 years at enrollment (rationale: this study focuses on determinants of early DKD over the course of T1D in adults)
• T1D duration \>5 years (rationale: DKD in T1D rarely manifests prior to 5 years of disease duration)
• HbA1c \<11% (rationale: HbA1c ≥ 11% exceeds the average HbA1c at most academic center and would limiting the generalizability of our study findings)