Diabetic Kidney Failure May Be Reversed with Low-Carbohydrate Diet
Researchers have found that by administering a low-carb, high-fat diet in mice, that diabetic kidney damage was reversed, and also uncovered an array of genes associated with kidney failure.
Researchers from Mount Sinai School of Medicine have for the first time determined that the ketogenic diet, a specialized high-fat, low carbohydrate diet, may reverse impaired kidney function in Type 1 and Type 2 diabetes. They also identified a previously unreported panel of genes associated with diabetes-related kidney damage, whose changes in expression were reversed by the diet. The findings were published online in the peer-reviewed journal PLoS ONE.
Charles Mobbs, PhD, Professor of Neuroscience and Geriatrics and Palliative Care Medicine at Mount Sinai School of Medicine, and his research team evaluated mice that were genetically predisposed to have Type 1 or 2 diabetes. The mice were allowed to develop diabetic nephropathy, or kidney damage. Half of the mice were put on the ketogenic diet, while the control group maintained a standard high carbohydrate diet. The researchers found that after eight weeks, molecular and functional indicators of kidney damage were reversed in the mice on the ketogenic diet. Microscopic analysis showed that kidney pathology in the model of Type 2 diabetes was partially reversed.
"Our study is the first to show that a dietary intervention alone is enough to reverse this serious complication of diabetes," said Dr. Mobbs. "This finding has significant implications for the tens of thousands of Americans diagnosed with diabetic kidney failure, and possibly other complications, each year."
The ketogenic diet is a low-carbohydrate, moderate protein, and high-fat diet typically used to control seizures in children with epilepsy. Many cells can get their energy from ketones, which are molecules produced when the blood glucose levels are low and blood fat levels are high. When cells use ketones instead of glucose for fuel, glucose is not metabolized. Since high glucose metabolism is thought to cause kidney failure in diabetes, researchers hypothesized that the ketogenic diet would block those toxic effects of glucose. Considering the extreme requirements of the diet, it is not a long-term solution in adults. However, Dr. Mobbs’ research indicates that exposure to the diet for a limited period may be sufficient to "reset" the gene expression and pathological process leading to kidney failure.
The researchers also identified a large array of cellular stress-related genes expressed during diabetic nephropathy not previously known to play a role in the development of this complication. The team found that the expression of these genes was also reversed in the mice on the ketogenic diet.
Dr. Mobbs and his team plan to continue to research the impact of the ketogenic diet and the mechanism by which it may reverse kidney failure in people with diabetes, and in age-related kidney failure. He believes the ketogenic diet could help treat some neurological diseases and retinopathy, a disease that results in vision loss.
"Knowing how the ketogenic diet reverses nephropathy will help us identify a drug target and subsequent pharmacological interventions that mimic the effect of the diet," said Dr. Mobbs. "We look forward to studying this promising development further."
This study was funded partly by the National Institutes of Health and by the Juvenile Diabetes Research Foundation.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. U.S. News & World Report consistently ranks The Mount Sinai Hospital among the nation's best hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.