To characterize the
lipid and
lipoprotein abnormalities in patients with
diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic
therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on
lipids and
lipoproteins, and adverse effects of marketed
lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding
lipid and
lipoprotein metabolism or guidelines on the treatment of
dyslipidemias in patients with
diabetes mellitus. An extensive review of
clofibrate was not included. The most common
dyslipidemia in patients with poorly controlled
insulin-dependent diabetes mellitus (
IDDM) is combined elevated
triglyceride and
cholesterol levels, with reduced
high-density lipoprotein (
HDL) cholesterol (mixed
hyperlipidemia).
Hypertriglyceridemia combined with a reduced
HDL cholesterol is the most common
dyslipidemia in patients with
noninsulin-dependent diabetes mellitus, but essentially any pattern of
dyslipidemia may be present. Small and dense
low-density lipoprotein (
LDL), glycosylation of
lipoproteins, and increased oxidized
lipoproteins may be present in patients with
diabetes mellitus; all contribute to accelerated atherosclerotic
cardiovascular disease.
Insulin therapy generally corrects quantitative
lipid abnormalities in patients with
IDDM, so
drug treatment is seldom indicated. Diet, exercise, and
insulin or oral sulfonylureas will improve
hypertriglyceridemia and low HDL concentrations, but do not always return them to normal.
Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on
lipids and
lipoproteins, patient age, adverse effect profile, patient tolerability, and
drug-disease and
drug-drug interactions. A
fibric acid derivative is the
drug of choice for marked
hypertriglyceridemia in patients with
diabetes mellitus.
Niacin can worsen
glycemic control, but it may be required in severe
hypertriglyceridemia,
hypercholesterolemia, or mixed
hyperlipidemia.
Bile-acid binding resins may accentuate
hypertriglyceridemia but may be useful in selected patients with marked
hypercholesterolemia and normal
triglycerides. Hydroxymethylglutaryl
coenzyme A reduced inhibitors are preferred in patients with elevated
LDL cholesterol and mild
hypertriglyceridemia. Patients with marked
lipid abnormalities or mixed
hyperlipidemias may require carefully dosed combinations of
lipid-lowering drugs.