Higher levels of blood urea nitrogen (BUN) are associated with an increased risk for incident diabetes, according to a study published in Kidney International.1
Using a big data approach, researchers followed 1,337,452 US veterans without diabetes for a median of 4.93 years (5,609,802.38 person-years).1 The participants were mainly white men with a mean age of 65.74 years.
Overall, 172,913 incident cases of diabetes were reported. Although there was no association between estimated glomerular filtration rate (eGFR) and the risk for diabetes in participants with a BUN of 25 mg/dL or less, the risk for diabetes increased significantly in participants with a BUN greater than 25 mg/dL at all eGFR levels, including those with an eGFR of 60 mL/minute/1.73 m2 or more.
The risk for diabetes was highest in participants with a BUN greater than 25 mg/dL and an eGFR less than 15 mL/minute/1.73 m2. Cubic spline regressions demonstrated that the risk for diabetes was exponentially increased with a greater BUN level. However, every 10 mL/minute/1.73 m2 decrease in eGFR was not associated with the risk for incident diabetes.
Two-stage residual inclusion analyses demonstrated that every 10 mg/dL increase in BUN concentration was associated with an increased risk for incident diabetes, independent of the effect of eGFR.
Previous mechanistic studies demonstrate the importance of the kidney in glucose homeostasis and suggest that higher levels of urea may increase insulin resistance and suppress insulin secretion.2,3 The investigators concluded that “the constellation of findings suggests that in advanced kidney disease and consistent with the experimental evidence, an elevated BUN level is associated with an increased risk of incident diabetes.”1
- Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus [published online December 10, 2017]. Kidney Int. doi: 10.1016/j.kint.2017.08.033
- D’Apolito M, Du X, Zong H, et al. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. J Clin Invest. 2010;120:203-213.
- Koppe L, Nyam E, Vivot K, et al. Urea impairs beta cell glycolysis and insulin secretion in chronic kidney disease. J Clin Invest. 2016;126:3598-3612.