Diabetic Macrovascular Disease

Patients with diabetes are at increased risk for macrovascular complications, particularly coronary artery disease and myocardial infarction. The magnitude of risk conferred by diabetes for cardiac complications is 2-4 times than in non-diabetic populations and is similar to that of a prior cardiovascular event in non-diabetic patients. Indeed, an elevated glucose level alone has been shown to be a risk factor for outcome in individuals hospitalized for a cardiac event. Macrovascular complications affect roughly 50% of patients with diabetes.

The current treatment for cardiovascular disease includes an armamentarium of beta blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor blockers and lipid lowering agents, as well as invasive surgical interventions. While significant progress has been made in disease treatment, the combination of underdiagnosis, poor therapy compliance and insufficient therapeutic effect is expected to result in continued development of macrovascular complications.

Diabetes accelerates nonenzymatic glycation of apolipoprotein B and the formation of its glyco-oxidized and oxidized products, which increase oxidative stress and stimulate untoward effects in tissues and cells of the vascular system. In preclinical studies, GLY220 has been shown to inhibit the formation of glycated apoB in the low density lipoprotein complex, and to prevent excess new cholesterol synthesis, the generation of atherosclerotic foam cells, and cellular activation leading to production of inflammatory cytokines. In animals with experimental diabetes, GLY220 reduces the profoundly elevated serum cholesterol concentrations and the increased lipid peroxidation and oxidative stress in the vessel wall.

Diabetic Macrovascular Disease References

Metabolism 59:658-663, 2010
Inhibiting low density lipoprotein glycation ameliorates increased cholesteryl synthesis in macrophages and hypercholesterolemia and aortic lipid peroxidation in streptozotocin diabetic rats

Metabolism 60:1683-1691, 2011
Effects of nonenzymatic glycation and fatty acids on functional properties of human albumin

Journal Diabetes & Metabolism 1:1-4, 2010
Rate of formation of glycated albumin revisited and clinical implications

Biochim Biophys Acta 1830:5480-5485, 2013:
Clinical, pathophysiological and structure/function consequences of modification of albumin by Amadori-glucose adducts