Chronic Kidney Disease Can Cause Diabetes, Study Finds

A recent collaborative study led by researchers at the University of Montreal Hospital Research Centre (CRCHUM) suggests that chronic kidney disease (CKD) could lead to diabetes. Findings from the study “Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease,” were published in the Journal of Clinical Investigation.

In CKD, renal function (the filtering and elimination of toxins from the blood) deteriorates progressively over time and leads to buildup of toxins in the blood that include urea (a major component of urine).

“In patients with chronic renal failure, the kidneys are no longer able to eliminate toxins. Urea is part of this cocktail of waste that accumulates in the blood. In nephrology textbooks, urea is presented as a harmless product. This study demonstrates the opposite, that urea is directly responsible for impaired insulin secretion in chronic kidney disease,” nephrologist Laetitia Koppe, PhD, the study’s first author, said in a press release.

Koppe said the study posed questions then provided answers.

“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. We observed the same abnormalities in samples of pancreatic cells from patients with chronic kidney disease,” Koppe said.

Dr. Vincent Poitout, the study’s senior author, a professor at the University of Montreal and a Canada Research Chair in Diabetes and Pancreatic Beta-Cell Function, said the team identified molecular mechanisms that may be responsible for increased blood glucose levels in patients with non-diabetic chronic kidney disease.

“Our observations in mice and in human samples show that the disease can cause secondary diabetes,” Poitout said.

The researchers also identified phosphofructokinase 1 as a key molecule in pancreatic beta cells.

“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. This creates oxidative stress and excessive glycosylation of phosphofructokinase 1, which causes an imbalance of blood glucose and may progress to diabetes,” said Poitout.

Researchers agree that further studies are required to validate the 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. One might then suggest therapeutic approaches, such as taking antioxidants, which may protect pancreatic beta cells and reduce the risk of developing diabetes,” Poitout said.