title: 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.
authors.affiliation: First Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides