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Kidney Int. 2018 Mar;93(3):741-752. doi: 10.1016/j.kint.2017.08.033. Epub 2017 Dec 11.

Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus.

Author information

1
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, St. Louis, Missouri, USA.
2
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, St. Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
3
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, St. Louis, Missouri, USA; Department of Epidemiology and Biostatistics, College for Public Health and Social Justice, Saint Louis University, St. Louis, Missouri, USA.
4
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, St. Louis, Missouri, USA; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
5
Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, St. Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; Renal Section, Medicine Service, VA St. Louis Health Care System, St. Louis, Missouri, USA; Institute for Public Health, Washington University in St. Louis, St. Louis, Missouri, USA. Electronic address: zalaly@gmail.com.

Abstract

Experimental evidence suggests that higher levels of urea may increase insulin resistance and 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. To study this, 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. Over a median follow-up of 4.93 years, there were 172,913 cases of incident diabetes. In joint risk models of estimated glomerular filtration rate (eGFR) and BUN. there was no association between eGFR and the risk of incident diabetes in those with a BUN of 25 mg/dl or less. However, the risk was significantly increased in those with a BUN over 25 mg/dl at all eGFR levels, even in those with an eGFR of 60 ml/min/1.73m2 or more (hazard ratio 1.27; confidence interval 1.24-1.31). The risk of incident diabetes was highest in those with BUN over 25 mg/dL and an eGFR under 15 ml/min/1.73m2 (1.68; 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 a BUN of 25 mg/dl or less, a BUN over 25 mg/dl was associated with increased risk of incident diabetes (1.23; 1.21-1.25). Every 10 ml/min/1.73m2 decrease in eGFR was not associated with risk of incident diabetes (1.00; 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 (1.15; 1.14-1.16). Thus, higher levels of BUN are associated with increased risk of incident diabetes mellitus.

KEYWORDS:

chronic kidney disease; diabetes; insulin resistance; urea; uremia; uremic toxins

PMID:
29241622
DOI:
10.1016/j.kint.2017.08.033
[Indexed for MEDLINE]
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