Elevated blood urea nitrogen (BUN) levels are associated with an increased risk of developing diabetes, according to a study in Kidney International.
The researchers analyzed a national cohort of more than 1.3 million US veterans enrolled in the VA Health Care System. All patients were initially free of diabetes. At the time of cohort entry, 8.77% of individuals had an elevated BUN level of greater than 25 mg/dL. Risk of incident diabetes associated with BUN was assessed over a median follow-up of nearly 5 years, including joint risk models of estimated glomerular filtration rate (eGFR) and BUN.
Among patients with a BUN level of 25 mg/dL or less, there was no association between eGFR and incident diabetes. However, an elevated BUN of 25 mg/dL or higher was significantly associated with diabetes, even in those with eGFR of 60 mL/min/1.73 m2: hazard ratio (HR) 1.27. For patients with elevated BUN and eGFR of less than 15 mL/min/1.73 m2, the HR increased to 1.68.
Diabetes risk increased progressively with BUN level on spline analysis. In analyses considering eGFR as a continuous covariate, elevated BUN was associated with an increased risk of diabetes, HR 1.23; while eGFR was not related to incident diabetes. In two-stage residual inclusion analyses, each 10 mg/dL increase in BUN was associated with an increase in diabetes risk.
Previous reports have linked higher urea levels to increased insulin resistance and suppressed insulin secretion. The new study demonstrates a significant increase in diabetes incidence in veterans with elevated BUN levels, independent of eGFR. The results suggest a bidirectional relationship between diabetes and kidney disease: in addition to the known increase in kidney disease risk associated with diabetes, urea may be associated with increased diabetes risk [Xie Y, et al. Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus. Kidney Int 2017; DOI: 10.1016/j.kint.2017.08.033].