Compositions and methods for treatment and delaying the onset of diabetes

Abstract

Disclosed herein are methods of delaying the onset or treating diabetes that comprises administering a uric acid lowering agent. The inventors have made the remarkable discovery that elevated uric acid levels are not a corollary to insulin resistance, but rather a primary mediator of insulin resistance. Specifically exemplified are methods that involve administering to a patient susceptible to development of diabetes a composition comprising a uric acid lowering agent in a regimen that maintains serum uric acid levels below at least 5.2 to 5.5 mg/dl.

What is claimed is: 
     
         1 . A method of lowering uric acid levels in a patient suffering from diabetes, said method comprising:
 administering to said patient a composition comprising a uric acid lowering agent according to a regimen effective to maintain a patient's average serum uric acid level at or below 5.5 mg/dl, wherein said uric acid lowering agent is a xanthine oxidase inhibitor, a uricosuric, a uricase, a pegylated uricase, a rasburicase, a urate channel inhibitor, or a URAT-1 blocker; wherein said administering treats or delays the onset of said diabetes.   
     
     
         2 . The method of  claim 1 , further comprising determining said patient's average serum uric acid prior to said administering. 
     
     
         3 . The method of  claim 1 , wherein said composition is administered over the course of at least one week. 
     
     
         4 . The method of  claim 1 , wherein said composition is administered over the course of at least 2 weeks. 
     
     
         5 . The method of  claim 1 , wherein said composition is administered over the course of at least 4 weeks. 
     
     
         6 . The method of  claim 1 , wherein said composition is administered according to a regimen to maintain the average serum uric acid level equal to or below 5.5 mg/dl for at least 2 weeks. 
     
     
         7 . The method of  claim 6 , wherein regimen is designed to maintain the average serum uric acid level equal to or below 5.5 mg/dl for at least 4 weeks. 
     
     
         8 . The method of  claim 6 , wherein regimen is designed to maintain the average serum uric acid level equal to or below 5.5 mg/dl for at least 8 weeks. 
     
     
         9 . The method of  claim 6 , wherein regimen is designed to maintain the average serum uric acid level equal to or below 5.5 mg/dl for at least 24 weeks. 
     
     
         10 . The method of  claim 6 , wherein regimen is designed to maintain the average serum uric acid level equal to or below 5.5 mg/dl for at least 2 years. 
     
     
         11 . The method of  claim 1 , wherein said composition is administered according to a regimen to maintain average serum uric acid levels between 4.5 mg/dl to 5.5 mg/dl for at least 12 weeks. 
     
     
         12 . The method of  claim 11 , wherein said composition is administered according to a regimen to maintain average serum uric acid levels between 4.5 mg/dl to 5.5 mg/dl for at least 1 year. 
     
     
         13 . A method lowering uric acid levels in a patient suffering from diabetes comprising:
 determining said patient's average serum uric acid level; and   administering to said patient a composition comprising a uric acid lowering agent according to a regimen effective to maintain said patient's average serum uric acid level between 4.5 mg/dl and 5.5 mg/dl for at least 4 weeks, wherein said uric acid lowering agent is a xanthine oxidase inhibitor, a uricosuric, a uricase, a pegylated uricase, a rasburicase, a urate channel inhibitor, or a URAT-1 blocker, wherein said administering treats or delays onset of said diabetes.   
     
     
         14 . The method of  claim 13 , wherein said administering occurs according to a regimen effective to maintain said patient's average serum uric acid level between 4.5 mg/dl and 5.5 mg/dl for at least 12 weeks. 
     
     
         15 . The method of  claim 13 , wherein said administering occurs according to a regimen effective to maintain said patient's average serum uric acid level between about 4.5 mg/dl and 5.5 mg/dl for at least 36 weeks. 
     
     
         16 . A method of lowering uric acid levels in a patient suffering from diabetes comprising administering to said patient a composition comprising a uric acid lowering agent according to a regimen effective to maintain said patient's average serum uric acid level between 4.5 mg/dl and 5.5 mg/dl for at least 2 weeks, wherein said uric acid lowering agent is a xanthine oxidase inhibitor, a uricosuric, a uricase, a pegylated uricase, a rasburicase, a urate channel inhibitor, or a URAT-1 blocker, wherein said administering treats or delays onset of said diabetes. 
     
     
         17 . The method of  claim 1 , wherein said uric acid lowering agent is a xanthine oxidase inhibitor. 
     
     
         18 . The method of claim  20 , wherein said xanthine oxidase inhibitor is febuxostat. 
     
     
         19 . The method of  claim 1 , wherein said uric acid lowering agent is benziodarone, benzbromarone or probenecid. 
     
     
         24 . The method of  claim 1 , wherein said uric acid lowering agent is a urate channel inhibitor. 
     
     
         25 . The method of  claim 1 , wherein said uric acid lowering agent is a URAT-1 blocker.