Abstract: TH-PO725

Kidney Disease and Risk of Incident Diabetes Mellitus

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • Xie, Yan, Clinical Epidemiology Center, Research and Development Service, Veterans Affairs St Louis Health Care System, St. Louis, Missouri, United States
  • Bowe, Benjamin Charles, Clinical Epidemiology Center, Research and Development Service, Veterans Affairs St Louis Health Care System, St. Louis, Missouri, United States
  • Li, Tingting, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Xian, Hong, Saint Louis University College for Public Health & Social Justice, St. Louis, Missouri, United States
  • Yan, Yan, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Al-Aly, Ziyad, Clinical Epidemiology Center, Research and Development Service, Veterans Affairs St Louis Health Care System, St. Louis, Missouri, United States
Background

Kidney disease is associated with disturbances in glucose and insulin homeostasis. Experimental evidence suggests that urea causes a state of insulin resistance and may also suppress insulin secretion. However, whether higher levels of Blood Urea Nitrogen (BUN) are associated with increased risk of incident diabetes mellitus in humans is not known.

Methods

We built a national cohort of 1,337,452 United States Veterans without diabetes to characterize the association of BUN and risk of incident diabetes. Cause specific survival analyses with time-varying variables were conducted.

Results

Over a median follow-up of 4.93 years, in joint risk models of eGFR and BUN; there was no association between eGFR and the risk of incident diabetes in those with BUN ≤25 mg/dl, the risk was significantly increased in those with BUN>25 mg/dl at all eGFR levels even in those with eGFR≥60 ml/min/1.73m2 (HR=1.27;CI=1.24-1.31). The risk of incident diabetes was highest in those with BUN >25 mg/dL and eGFR<15 ml/min/1.73m2 (HR=1.68;CI=1.51-1.87). Spline analyses of the relationship between BUN and risk of incident diabetes showed that risk was progressively higher as BUN increased. In models where eGFR was included as a continuous covariate; compared to BUN≤25 mg/dl, BUN>25 mg/dl was associated with increased risk of incident diabetes (HR=1.23;CI=1.21-1.25); every 10 ml/min/1.73m2 increase in eGFR was not associated with risk of incident diabetes (HR=1.00;CI=1.00-1.01). Two-stage residual inclusion analyses showed that independent of the impact of eGFR, every 10 mg/dL increase in BUN concentration was associated with increased risk of incident diabetes (HR=1.15;CI=1.14-1.16).

Conclusion

Our results suggest that higher levels of BUN are associated with increased risk of incident diabetes mellitus. A bidirectional nexus (between diabetes and kidney disease) likely exists, in that diabetes causes kidney disease, and elevated levels of urea-often present in the context of advanced kidney disease-are associated with increased risk of incident diabetes.

Funding

  • Veterans Affairs Support