New Treatment Method for Prediabetes in Patients with Kidney Disease
Researchers find prebiotics could lower risk of heart problems in patients with kidney disease.
-- by Alexia Severson
Individuals with kidney disease may be at a high risk for prediabetes due to the retention of certain compounds normally excreted by the kidneys in healthy individuals, according to a study published in JASN, the Journal of the American Society of Nephrology. These findings could be used to prevent prediabetes, or insulin resistance, in kidney disease patients and lower their risk of developing heart problems.
Cardiovascular disease is the number-one killer of patients with chronic kidney disease (CKD), and insulin resistance, a lowered level of response to insulin circulating in the blood, is a major risk factor in these patients. Researchers are not sure why patients with CKD often develop insulin resistance, but they hypothesize that retention of compounds normally removed from the blood and excreted in the urine may play a role.
While more than 90 compounds were described to accumulate in CKD patients, researchers chose to focus on one of the most toxic of these compounds, called p-cresyl sulfate (PCS), a toxin produced by gut bacteria from dietary proteins. PCS is retained in CKD patients and poorly removed by most dialysis techniques.
The Expert Take
Study author Christophe Soulage, Ph.D. and his colleagues of the Université de Lyon in Villeurbanne, France found that administering PCS to mice with normal kidney function for four weeks triggered insulin resistance, loss of fat mass, and a redistribution of lipids in the muscles and liver, mimicking features associated with CKD.
“This observation allowed us to look for new strategies to prevent accumulation of this compound, especially since this toxin is poorly removed by common dialysis methods,” says Soulage. “We demonstrated in a mouse model of CKD that a prebiotic, namely a kind of dietary fibers, reduced blood levels of these compounds, and prevented insulin resistance and lipid abnormalities.”
Soulage said the use of prebiotics, devoid of harmful side effects, could be used to prevent metabolic disease in CKD patients.
“Because insulin resistance is an important cardiovascular risk factor, novel therapeutic approaches like prebiotics that could decrease PCS more substantially than currently available strategies must be developed,” he says. “We are now trying to give prebiotics to patients with CKD.”
Source and Method
Researchers performed an intraperitoneal glucose tolerance test and insulin tolerance test on the mice after an overnight fast. Blood glucose values were determined from a drop of blood sampled from the terminal portion of the tail, using an automatic glucose monitor.
To study insulin signaling in skeletal muscle, mice were injected with insulin or saline solution 60 minutes after the last administration of PCS. Mice were anesthetized with sodium pentobarbital 30 minutes after the injection.
All animal experiments were performed under the authorization CarMeN lab, Direction Départementale des Services Vétérinaires du Rhône and carried out according to the guidelines laid down by the French Ministère de l’Agriculture and the E.U. Council Directive for the Care and Use of Laboratory Animals.
According to a Summary Health Statistics for U.S. Adults 2010 survey, conducted by the Centers for Disease Control and Prevention, 3.9 million non-institutionalized adults are diagnosed with kidney disease. And according to the National Diabetes Education Program, an estimated 79 million adults aged 20 and older have prediabetes.
The findings in this study provide valuable insight as to how to prevent the development of prediabetes and diabetes. This research also gives doctors a better understanding of what causes prediabetes and why patients with CKD might be at a high risk for developing the disease.
And while Soulage said prebiotics could be an effective treatment in the fight against prediabetes, according to NDEP, people can prevent or delay prediabetes from progressing to diabetes by losing weight and increasing physical activity.
In a study published in 2007 in Nephrology Dialysis Transplantation, researchers assessed the influence of diabetic and prediabetic state on the development of contrast-induced nephropathy (CIN) in chronic kidney disease patients undergoing coronary angiography. They determined that patients with diabetes mellitus (DM) are at a higher risk of developing CIN, but patients with pre-DM are not at as high of a risk for developing CIN as diabetes patients.
Another study published in CJASN, the Clinical Journal of the American Society of Nephrology, in 2010, compared the community prevalence of CKD among people with diagnosed diabetes, undiagnosed diabetes, prediabetes, or no diabetes. Results in this study showed that CKD prevalence was high among people with undiagnosed diabetes and prediabetes. Researchers concluded that “these individuals might benefit from interventions aimed at preventing development and/or progression of both CKD and diabetes.”
Researchers in a study published in Diabetes Care in 2005 also assessed the association between kidney disease and prediabetes. Scientists concluded that “cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease.” They also determined that clinical trials are a good way to measure whether vascular risk factor modification can slow the decline of kidney function among those with prediabetes.