Several proteins are known to be glycosylated in patients with diabetes mellitus. In this proposal, I plan to test the hypothesis that low density lipoproteins (LDL) and high density lipoproteins (HDL) are glycosylated in circulation, that glycosylation is more extensive in diabetic patients and is related to their metabolic control. In addition, structure-function relationship of in vitro glycosylated lipoproteins will be carried out, in an attempt to examine whether glycosylation renders these lipoproteins more "atherogenic". Methods for measuring glycosylation in isolated human lipoproteins will incldue affinity chromatography for separating glycosylated amino acids, high pressure liquid chromatography for measuring hydrolysis products of glycosylated amino acids and/or radioimmunoassay using specific monoclonal antibodies. Patients for isolating the lipoproteins (and examining the effects of diabetic control on their glycosylation) will be selected from among a diabetic population being followed at the Washington University out-patient clinics. Long-term objectives include refining the above methodology for studying the etiology of diabetic complications in general, and of those related to alterations in lipoproteins in particular. Future application of glycosylated lipoprotein measurements to assessing metabolic diabetic control is a distinct possibility. The performance of this study involves both clincal and basic laboratory research. It is hoped that as a result of this investigation our nderstanding of diabetic complications as releated to nonenzymatic glycosylation on one hand, and progressive atherosclerosis on the other, will be enhanced, and that more insight will be gained into the structure-function relationship of the lipoproteins.