Hyperlipidemia and its treatment are currently recognized as important modulators of cardio-vascular mortality in the presence of disordered
glucose control. On the other hand, the effects of
hyperglycemia and its treatment on
hyperlipidemia are not widely appreciated.
Hyperglycemia is commonly associated with an increase in intestinal
lipoproteins and a reduction in
high-density lipoprotein (HDL). This could be a consequence of
hyperglycemia-induced glycation of
lipoproteins, which reduces the uptake and catabolism of the
lipoproteins via the classical
low-density lipoprotein (
LDL) receptor. A high
dietary carbohydrate load increases the glycation of intestinal
lipoproteins, prolongs their circulation, and increases their plasma concentration.
Hyperglycemia also leads to inhibition of
lipoprotein lipase, further aggravating
hyperlipidemia. Circulating
advanced glycation end-products (AGEs) also bind
lipoproteins and delay their clearance, a mechanism that has particularly been implicated in the
dyslipidemia of
diabetic nephropathy. As uptake via
scavenger receptors is not inhibited, glycation increases the proportion of
lipoproteins that are taken up via inflammatory cells and decreases the proportion taken up by hepatocytes via classical
LDL receptors. This promotes the formation of
atheromatous plaques and stimulates
inflammation.
Hyperglycemia increases the formation of
oxidized LDL and
glycated LDL, which are important modulators of
atherosclerosis and cardiovascular death. The risk of cardiovascular death is increased by even short-term derangement of
blood sugar control, owing perhaps to the glycation of
lipoproteins and other critical
proteins.
Glycated LDL could prove very useful in measuring the effect of
hyperglycemia on
cardiovascular disease, its risk factors, and its complications. Comparing different
glucose-lowering and
lipid-lowering drugs in respect to their influence on
glycated LDL could increase knowledge of the mechanism by which they alter cardiovascular risk.