Chronic Kidney Disease May Cause Diabetes

Although it was previously found that kidney disease can cause diabetes, the diseases also have an inverse relationship.

Researchers in a recent study discovered a new facet of the relationship between chronic kidney disease (CKD) and type 2 diabetes.

“We identified molecular mechanisms that may be responsible for increased blood glucose levels in patients with non-diabetic chronic kidney disease,” said study principal investigator Vincent Poitout, DVM, PhD. “Our observations in mice and in human samples show that the disease can cause secondary diabetes.”

They discovered that patients with non-diabetic CKD can potentially develop diabetes due to a build-up of urea in the bloodstream, according to the study published by the Journal of Clinical Investigation.

“About half of those affected by chronic kidney disease have abnormal blood sugar levels. I wondered why. We conducted experiments in mice and found impaired insulin secretion from pancreatic beta cells, as observed in diabetes,” said researcher Laetitia Koppe, MD, PhD. “We observed the same abnormalities in samples of pancreatic cells from patients with chronic kidney disease.”

Once kidneys cannot filter toxins properly, waste builds up in the blood. Researchers found that urea, a waste product excreted in urine, can build up and become toxic.

While urea is generally thought of as harmless, researchers discovered that is directly responsible for impaired insulin secretion in CKD, according to the study. Researchers also found that protein phosphofructokinase 1 in pancreatic beta cells is also altered by increase urea in the blood.

“The function of this protein is altered by an increase in blood urea, which occurs in chronic kidney disease. Increased urea causes impaired insulin secretion from the pancreatic beta cells," Dr Poitout said. “This creates oxidative stress and excessive glycosylation of phosphofructokinase 1, which causes an imbalance of blood glucose and may progress to diabetes.”

Researchers said their findings are significant because it uncovers a previously unknown relationship between CKD and diabetes.

“Further studies are required to validate these findings in humans. But if our observations are confirmed, it will mean that patients with non-diabetic chronic kidney disease are at risk of developing diabetes,” Dr Poitout concluded. “One might then suggest therapeutic approaches, such as taking antioxidants, which may protect pancreatic beta cells and reduce the risk of developing diabetes.”