Materials and methods relating to the diagnosis and treatment of diabetes and obesity

Abstract

The diagnosis of diabetes based on the level or ratio of P- and A-type inositolphosphoglycans (IPGs) in a sample from a patient, and the use of P- and A-type IPGs or their antagonists in the treatment of diabetes is disclosed. In particular, the present invention provides treatment of IDDM or lean type II diabetes (NIDDM) with a mixture of P- and A-type mediators, and treatment of obese type II diabetes (NIDDM) with a P-type mediator and/or an A-type antagonist.

1 . A method of diagnosing diabetes, the method comprising determining the level or ratio of P- and/or A-type inositolphosphoglycans (IPGs) in a biological sample from a patient.  
     
     
         2 . The method of  claim 1  wherein the biological sample is a blood or urine sample.  
     
     
         3 . The method of  claim 1  or  claim 2  wherein the level of the P- or A-type IPGs is determined using an assay for one of their biological activities.  
     
     
         4 . The method of  claim 3  wherein the level of the P-type IPGs is determined in an assay measuring activation of pyruvate dehydrogenase phosphatase by P-type IPGs.  
     
     
         5 . The method of  claim 3  wherein the level of the A-type IPGs is determined in an assay measuring activation of lipogenesis by A-type IPGs in isolated adipocytes.  
     
     
         6 . The method of  claim 1  or  claim 3 , wherein the level of the P- or A-type IPGs is determined using a binding agent capable of specifically binding P- or A-type IPGs.  
     
     
         7 . The method of  claim 6  wherein the binding agent is an anti-IPG antibody or an IPG specific binding protein.  
     
     
         8 . The method of  claim 1  or  claim 2  wherein the method comprises the steps of: 
 (a) contacting a biological sample obtained from the patient with a solid support having immobilised thereon a first binding agent having binding sites specific for one or more P-type IPGs and a second binding agent having binding sites for one or more A-type IPGs;  
 (b) contacting the solid support with one or more labelled developing agents capable of binding to unoccupied binding sites, bound IPGs or occupied binding sites; and,  
 (c) detecting the label of the developing agents specifically binding in step (b) to obtain values representative of the levels of the P- and A-type IPGs in the sample.  
 
     
     
         9 . The method of  claim 8  comprising the further step of: 
 (d) using the values to obtain a ratio of the P- and A-type IPGs in the sample.  
 
     
     
         10 . Use of P- or A-type inositolphosphoglycans (IPGs), or antagonists to P- or A-type IPGs, in the preparation of a medicament for the treatment of diabetes.  
     
     
         11 . The use of  claim 10  wherein the medicament is formulated to provide a ratio of P- and A-type IPGs in a patient having diabetes of from about 4:1 to about 6:1.  
     
     
         12 . The use of  claim 11  wherein the ratio of P- and A-type IPGs is about 6:1 for a male patient and about 4:1 for a female patient.  
     
     
         13 . Use of a P-type IPG arid/or an A-type IPG antagonist in the preparation of a medicament for the treatment of obese type II diabetes.  
     
     
         14 . Use of a mixture of P-type and A-type IPGs in the preparation of a medicament for the treatment of IDDM or lean type II diabetes (NIDDM).  
     
     
         15 . The use of  claim 14  wherein the P- and A-type IPGs are in the ratio of about 6:1 for male patients and about 4:1 mixture for female patients.  
     
     
         16 . A pharmaceutical composition comprising a P-type IPG and/or an A-type IPG antagonist in combination with a pharmaceutically acceptable carrier.  
     
     
         17 . A pharmaceutical composition comprising a mixture of P- and A-type IPGs in combination with a pharmaceutically acceptable carrier.  
     
     
         18 . The pharmaceutical composition of  claim 17  wherein the P/A-type IPG ratio is from about 4:1 to about 6:1.  
     
     
         19 . A method of screening for P- or A-type IPG antagonists, the method comprising: 
 (a) contacting a candidate antagonist and a P- or A-type IPG in an assay for a biological property of the P- or A-type IPG under conditions in which the IPG and the candidate antagonist can compete;    (b) measuring the biological property of the IPG; and,    (c) selecting candidate antagonists which reduce the biological activity of the IPG.