Reversal of Diabetic Nephropathy by a Ketogenic Diet

[greg10]

Diabetes is the most common cause of ESRD, resulting in about one-third of  of new ESRD cases.  NIDDM (Type II diabetes) causes 80 percent of the ESRD in African Americans and Native Americans.

Ketogenic diets are composed of about 85% fat.  Note that according to results from another study, which was published in the March 23 issue of the European Journal of Clinical Nutrition, 70 percent of the Yup'ik Eskimo population is considered to be overweight or obese, but due to their increased intake of omega-3 fats they are at a lower risk than most other Americans for diabetes and cardiovascular disease, including heart attacks.

Reversal of Diabetic Nephropathy by a Ketogenic Diet

Michal M. Poplawski1, Jason W. Mastaitis2, Fumiko Isoda1, Fabrizio Grosjean3, Feng Zheng3, Charles V. Mobbs1*

1 Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York, United States of America, 2 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America, 3 Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, New York, United States of America

Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.