Compositions and methods for treatment and prevention of hyperuricemia related health consequneces

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 5.5 mg/dl, or below at least 5.2 mg/dl.

1 . A method of preventing or delaying the onset of insulin resistance in a patient comprising:
 determining said patient's average serum uric acid level;   and   administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level at or below 5.5 mg/dl.   
   
   
       2 . The method of  claim 1 , further comprising determining said patient's average serum uric acid occurs 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 about 3.5 mg/dl to about 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 about 3.5 mg/dl to about 5.5 mg/dl for at least 1 year. 
   
   
       13 . A method of preventing, delaying the onset of, or treating insulin resistance of a patient comprising:
 determining said patient's average serum uric acid level;   and   administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level between about 4.0 mg/dl and 5.5 mg/dl for at least 4 weeks.   
   
   
       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 about 4.0 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 4.0 mg/dl and 5.5 mg/dl for at least 36 weeks. 
   
   
       16 . A composition comprising UALA and at least one antioxidant. 
   
   
       17 . A combination therapy comprising the administration concomitantly, simultaneously or sequentially, of therapeutically effective amounts of a combination of UALA and antioxidant. 
   
   
       18 . The combination therapy of the  claim 17 , wherein UALA is administered according to a dosage to lower a patient's average serum uric acid level below 5.5 mg/dl. 
   
   
       19 . The combination therapy of  claim 17  wherein UALA is administered according to a regimen effective to maintain said patient's average serum uric acid level between about 4.0 mg/dl and 5.5 mg/dl for at least 2 weeks. 
   
   
       20 . A method of reducing the risk of developing, delaying the onset of, or treating metabolic syndrome in a patient in need thereof comprising administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level below 5.5 mg/dl for at least 12 weeks. 
   
   
       21 . The method of  claim 20 , wherein said patient is determined to have asymptomatic hyperuricemia. 
   
   
       22 . A method of reducing the risk of developing, delaying the onset of, or treating insulin resistance in patient in need thereof comprising administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level between about 4.0 mg/dl and 5.5 mg/dl for at least 12 weeks. 
   
   
       23 . The method of  claim 22 , wherein said patient is determined to have asymptomatic hyperuricemia. 
   
   
       24 . A method of reducing the risk of developing, delaying the onset of, or treating obesity associated with metabolic syndrome in a patient in need thereof comprising administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level below 5.5 mg/dl for at least 12 weeks. 
   
   
       25 . A method of reducing the risk of developing hyperuricemia-induced health consequences in a patient experiencing asymptomatic hyperuricemia with a uric acid level higher than 5.5 mg/dl, said method comprising administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level at or below 5.5 mg/dl for at least 12 weeks. 
   
   
       26 . The method of  claim 25 , wherein said administering occurs according to a regimen effective to maintain said patient's average serum uric acid level between about 4.0 mg/dl and 5.5 mg/dl for at least 52 weeks. 
   
   
       27 . The method of  claim 25 , wherein said hyperuricemia-induced health consequences are insulin resistance, obesity, hypertriglyceridemia, nonalcoholic fatty liver disease, metabolic syndrome or diabetic nephropathy. 
   
   
       28 . A method of delaying the onset of or reducing the risk of developing diabetic nephropathy of a patient with diabetes and a uric acid level higher than 5.5 mg/dl, said method comprising administering to said patient a composition comprising UALA according to a regimen effective to maintain said patient's average serum uric acid level below 5.5 mg/dl for at least 12 weeks. 
   
   
       29 . The method of  claim 27 , wherein said UALA is allopurinol or febuxostat, or both.