LOUIS—For years, research has shown that patients with diabetes have an increased risk of kidney disease. But what about the reverse?

A new study published in the journal Kidney International provides evidence that kidney dysfunction also ups the risk of developing diabetes.1

Researchers from the St. Louis VAMC and Washington University School of Medicine also pointed out that urea appears to be the link between the two diseases, explaining that the nitrogen-containing waste product in blood comes from the breakdown of protein in foods. While kidneys typically remove urea from the blood, the substance can build up when kidney function falters.

Study authors further suggested that, armed with the information, clinicians can help patients lower urea levels through medication and diet—which also might decrease the risk of diabetes development.

“We have known for a long time that diabetes is a major risk factor for kidney disease, but now we have a better understanding that kidney disease, through elevated levels of urea, also raises the risk of diabetes,” explained senior author Ziyad Al-Aly, MD.“When urea builds up in the blood because of kidney dysfunction, increased insulin resistance and impaired insulin secretion often result.”

Medical records in national VA databases were analyzed to determine the relationship between kidney disease and diabetes. The study team reviewed records of 1.3 million adults without diabetes over a five-year period, beginning in 2003. Based on a routine blood test, they determined that the amount of urea nitrogen indicated 117,000 of those patients without diabetes, 9%, had elevated urea levels, a measure of poor kidney function.

“That figure—9 percent of people with high urea levels—remained relatively constant over time,” Al-Aly emphasized. “It is also reflective of the general population.”

In each year studied, the researchers documented new cases of diabetes in 2,989 of every 100,000 people with low urea levels and 3,677 new cases of diabetes among those with high urea levels. Ultimately, they determined that patients with high urea levels had a 23% greater risk of developing diabetes.

“The risk difference between high and low levels is 688 cases of diabetes per 100,000 people each year,” Al-Aly said. “This means that for every 100,000 people, there would be 688 more cases of diabetes each year in those with higher urea levels.”

Al-Aly said the study was inspired by a mouse study published in 2016 which found that many of the animals had elevated urea levels, resulting in insulin resistance and impaired insulin secretion.

“I read the study with excitement and intrigue, and I thought, ‘We have to test this in humans,’” Al-Aly recounted. “Our results were almost an exact replica of the mouse study. The results showed a clear relationship between urea levels and risk of 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. Kidney Int. 2017 Dec 7. pii: S0085-2538(17)30676-2. doi: 10.1016/j.kint.2017.08.033. [Epub ahead of print] PubMed PMID: 29241622.