Methods for improving diabetes management

Abstract

A method for determining the levels of biomarkers, specifically, advanced glycation end products (AGEs) and oxidation products (Ops) in a biological sample such as a plasma ultrafiltrate, is used to determine a patient's risk and/or rate of developing diabetes related nephropathy. The preferred biomarkers to measure include Nε-(1-carboxyethyl-lysine (CEL), methylglyoxyl-derived hydroimidazolone (MGHI) and Nε-carboxymethyllysine (CML). Also provided herein is a method of diabetic care which includes determining a diabetic patient's risk of developing diabetes related kidney disease and adjusting the patient's treatment regimen to include in addition to glucose lowering agents, additional treatments such as medications that modify the renin-angiotensin system, or specialized diets with low levels of AGEs or oxidative products.

I claim: 
     
         1 . A method for determining the risk or rate of an individual of developing diabetic nephropathy, eye disease or cardiovascular complications comprising:
 determining the levels of two or more biomarkers purified from a biological sample,   wherein the biomarkers are selected from the group consisting of lysine advanced glycation end products, arginine advanced glycation end products, and oxidation products, and   comparing the metabolite levels to standard values, wherein the level of the biomarkers indicates the risk of developing diabetic complications or the rate of developing diabetic complications.   
     
     
         2 . The method of  claim 1 , wherein the biomarker is selected from the group consisting of N ε -carboxy methyl-lysine (CML), N ε -carboxy ethyl-lysine (CEL), Glyoxal hydroimidazolone (GH1), Methylglyoxal hydroimidazolone (MGH1); 3-Deoxyglucosone Hydroimidazolone (3DGH), methionine sulfoxide (MetSO), and 3-nitrotyrosine (3-NT). 
     
     
         3 . The method of  claim 1  wherein the advanced glycation end products are selected from the group consisting of N ε -(1-carboxyethyl-lysine (CEL), methylglyoxyl-derived hydroimidazolone (MGHI) and N ε -carboxymethyllysine (CML). 
     
     
         4 . The method of  claim 3  wherein the plasma levels of CML, CEL, and MG-H1, alone or in combination with the level of HbA1c, are measured as indicators of early progression of diabetic nephropathy. 
     
     
         5 . The method of  claim 4  wherein values of CEL of less than 0.042, MGHI less than 0.103 and CML less than 0.062), indicate that the individual has a low risk or slow rate of development of diabetic nephropathy. 
     
     
         6 . The method of  claim 5  wherein values of CEL between 0.020-0.042, MGHI between 0.030-0.103 and CML between 0.033-0.062, indicate that the individual has a low risk or slow rate of development of diabetic nephropathy. 
     
     
         7 . The method of  claim 1  comprising obtaining the biological sample from an individual and determining the level of the biomarkers using Liquid Chromatography/Triple Quadrupole Mass Spectroscopy (LC-MS/MS) to purify and quantify the biomarkers. 
     
     
         8 . The method of  claim 1  wherein the sample is a urine sample or a plasma sample. 
     
     
         9 . The method of  claim 1  wherein the sample is a plasma ultrafiltrate. 
     
     
         10 . The method of  claim 7  wherein the LC-MS/MS stationary phase is C18 with heptafluorobutyric acid being the ion pairing agent. 
     
     
         11 . The method of  claim 1  wherein the individual is determined to be at risk of developing diabetic nephropathy. 
     
     
         12 . The method of  claim 1  wherein the individual is determined to be at risk of developing diabetic retinopathy. 
     
     
         13 . The method of  claim 1  wherein the individual is determined to be at risk of developing diabetic cardiovascular complications. 
     
     
         14 . The method of  claim 1  further comprising providing a report with the risk or rate of development of diabetic complications. 
     
     
         15 . The method of  claim 14  further comprising providing recommended treatment options for the individual at risk or having an elevated rate of development of diabetic complications. 
     
     
         16 . The method of  claim 15  wherein the treatment options are selected from the group consisting of glucose lowering agents, medications that modify the renin-angiotensin system, and specialized diets with low levels of AGEs or oxidative products. 
     
     
         17 . The method of  claim 1  wherein the individual has not been diagnosed with diabetic nephropathy, eye disease or cardiovascular complications. 
     
     
         18 . A kit comprising reagents for use in testing a sample using the method of  claim 1 . 
     
     
         19 . The kit of  claim 18  comprising reagents for testing for levels of two or more biomarkers selected from the group consisting of N ε -carboxy methyl-lysine (CML), N ε -carboxy ethyl-lysine (CEL), Glyoxal hydroimidazolone (GH1), Methylglyoxal hydroimidazolone (MGH1); 3-Deoxyglucosone Hydroimidazolone (3DGH), methionine sulfoxide (MetSO), and 3-nitrotyrosine (3-NT). 
     
     
         20 . The kit of  claim 18  comprising reagents for determining the level of the biomarkers using Liquid Chromatography/Triple Quadrupole Mass Spectroscopy (LC-MS/MS).