It remains unclear whether
insulin improves
dyslipidemia in patients with
type 2 diabetes mellitus. Small dense
low-density lipoprotein (sd-
LDL) particles are recognized as a powerful risk factor for
coronary heart disease and are often elevated in
type 2 diabetes mellitus. We examined the effect of intensive
insulin therapy on sd-
LDL particles and
triglyceride (TG)-rich
lipoprotein subspecies. Intensive
insulin therapy (
insulin aspart [
NovoRapid, Tokyo, Japan] before each meal and
isophane insulin suspension at bedtime) was given to poorly controlled type 2 diabetic patients (n = 46) who were on high doses of sulfonylureas. Fasting serum samples were collected before and 14 days after the commencement of
insulin therapy.
Low-density lipoprotein size was measured by gradient gel electrophoresis, and the small dense
LDL cholesterol (sd-
LDL-C) concentration was measured by a new precipitation method.
Chylomicrons (Svedberg flotation unit >400),
very low-density lipoprotein 1 (VLDL1) (Sf, 60-400), and VLDL2 (Sf, 20-60) were separated by ultracentrifugation. Serum
apolipoprotein B-48 and
lipoprotein lipase levels were measured by the
enzyme immunoassay method. Serum
glucose and
glycoalbumin levels were substantially decreased by
insulin treatment. The
LDL size increased (25.8-26.0 nm, P < .05) and the sd-
LDL-C level was significantly reduced (44-34 mg/dL, P < .005).
Apolipoproteins B-48 and C-III were decreased, whereas
lipoprotein lipase was increased.
Triglyceride levels in
chylomicrons, VLDL1, and VLDL2 all showed a decrease. Changes of sd-
LDL-C or
LDL size were associated with changes of the TG levels in the major TG-rich
lipoprotein subspecies. These results suggest that intensive
insulin therapy decreases atherogenic sd-
LDL particles by reducing TG in TG-rich
lipoproteins. We did not find any specific relationship between VLDL1 and sd-
LDL during
insulin treatment.