title: Effect of pioglitazone on various parameters of insulin resistance including lipoprotein subclass according to particle size by a gel-permeation high-performance liquid chromatography in newly diagnosed patients with type 2 diabetes.
abstract: Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects. The aim of this study was to obtain a better understanding of the mechanism involved in the insulin sensitizing effect of pioglitazone. A total of 50 newly diagnosed patients with type 2 diabetes were enrolled in this study and divided into two groups, 25 of who were treated with 15 mg/day pioglitazone and 25 with 500 mg/day metformin for 12 weeks. Changes in various parameters of insulin resistance including lipoprotein subclass according to particle size determined by high performance liquid chromatography, as well as glucose metabolism, were monitored to determine the relationship between lipoprotein subclass and other insulin resistance parameters. Both pioglitazone and metformin treatment were associated with significant reductions in hyperglycemia, HOMA-IR and HbA1c levels. Pioglitazone treatment, but not metformin treatment resulted in significant reductions in serum large very low-density lipoprotein (VLDL: 44.5-64.0 nm) and increases in serum adiponectin levels (both <0.001). In the pioglitazone group, the change in large VLDL levels correlated positively with changes in HbA1c (r=0.468, P=0.0174), HOMA-IR (r=0.593, P=0.0014), very small LDL (r=0.714, P<0.0001) and net electronegative charged modified-LDL (r=0.412, P=0.0399), and inversely with changes in adiponectin level (r=-0.526, P=0.0061). The results in this study suggest that the hypoglycemic effect of pioglitazone is achieved mainly through improvement of hepatic insulin resistance, and that pioglitazone may have an antiatherosclerotic effect by decreasing serum atherogenic modified-LDL and by increasing adiponectin.
authors.affiliation: Department of Internal Medicine, Yamashiro Public Hospital, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nakano
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ishihara
authors.forename: Tooru
authors.initials: T
authors.lastname: Takashima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Aya
authors.initials: A
authors.lastname: Fujinami
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ogata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D017668:Age of Onset; D050218:Body Fat Distribution; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance; D008074:Lipoproteins / Q000032:analysis* / Q000097:blood / Q000145:classification; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D010316:Particle Size; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone