People with Chronic Kidney Disease May Be at Risk of Diabetes

People with Chronic Kidney Disease May Be at Risk of Diabetes

Patients with chronic kidney disease may be at higher risk of developing diabetes, according to a study by investigators at the University of Montreal Hospital Research Centre (CRCHUM).

Their study, “Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease,” published in The Journal of Clinical Investigation, reveals that urea, one of the waste products that builds up upon kidney failure, can affect insulin secretion.

“We 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,” Dr. Vincent Poitout, CRCHUM director and principal investigator of the study, said in a press release.

Chronic kidney disease (CKD) is characterized by the progressive and irreversible loss of kidney function, resulting in the accumulation of waste products in the blood that are not properly filtered by the kidneys. Given that these waste products can be toxic and affect other organs, CKD patients often require dialysis (or a kidney transplant) to properly eliminate the toxins from their blood.

Several studies have reported that type 2 diabetes can cause CKD, and now the research team has shown that the opposite may also be true.

The researchers were intrigued by studies reporting that approximately half of all CKD patients had abnormal blood sugar levels. Using mice models the team found that insulin-producing pancreatic beta cells were impaired, as is the case in diabetes patients. Pancreatic cell isolated from CKD patients also had the same abnormal insulin secretion — a consequence, the researchers found, of excessive urea accumulation. This waste product is normally filtered by the kidneys and excreted in the urine, but builds in CKD patients’ blood. This finding was surprising, as urea was thought to be one of the more harmless of these toxins.

“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,” Koppe said.

Koppe and Poitout found that urea affects the function of a particular protein, called phophofrutokinase 1 (PFK1), involved in the metabolism of glucose. Its accumulation also led to an increase in oxidative stress and glycosilation (a type of protein modification) of PFK1, resulting in a  blood glucose imbalance that could lead to 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. 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.

Leave a Comment