Diabetics exhibit a greater incidence of cardiovascular disease than n
on-diabetics. The vascular changes that occur are well documented and
are thought to promote other clinical manifestations such as cardiomyo
pathy. Research has shown that the pathogenic events in the myocyte ma
y occur independently of atherosclerotic processes. The atheroscleroti
c changes in diabetes involve non-enzymatic glycation of extracellular
basement membrane proteins. We hypothesize that intracellular glycati
on events occur in cardiac tissue that alter intermediary metabolism,
particularly Ca2+ homeostasis, which leads to cell dysfunction. Additi
onally, we hypothesize that the high steady state intracellular concen
trations of unphosphorylated creatine may offer protection against the
formation of advanced glycation endproducts by reacting directly with
glucose metabolites that may have reached toxic levels in the myocyte
of diabetics.