Intensive insulin therapy reduces small dense low-density lipoprotein particles in patients with type 2 diabetes mellitus: relationship to triglyceride-rich lipoprotein subspecies

Abstract

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.