title: Alterations of plant sterols, lathosterol, oxidative stress and inflammatory markers after the combination therapy of ezetimibe and statin drugs in type 2 diabetic patients.
abstract: The elevation of serum plant sterols in addition to serum LDL-cholesterol (LDL-C) is one of the important risk factors for coronary heart disease. We investigated how to alterations of serum hepatic synthesised cholesterol and plant sterols levels, clinical markers for inflammation and oxidative stress after combination therapy with ezetimibe, an inhibitor of cholesterol transporter in the small intestinal colon, and statin drugs in type 2 diabetic patients. Studies were conducted in 28 patients with type 2 diabetes mellitus complicated with dyslipidemia. Patients were divided into 3 groups as follows: the 1st group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with mild statin drug (MS+E group), and the 2nd group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with strong statin drug (SS+E group), and then the 3rd group is 14 patients treated with 10mg ezetimibe alone without pretreatment with any statin drugs (naïve E group). In addition to various metabolic markers, serum plant sterols such as sitosterol and campesterol, and hepatic synthesised cholesterol such as lathosterol were measured by the gas liquid chromatography. Serum highly sensitive CRP (hsCRP) as an inflammation marker, and then malonyldealdehyde (MDA) and carbonyl-modified protein (CMP) as an oxidative stress were assayed by the conventional method, respectively. Fasting plasma glucose and serum glucosylated HbA1c (JDS value) did not show any significant changes after administration of ezetimibe in whole groups. Serum LDL-C was reduced significantly and serum triglyceride exhibited a tendency of reduction in whole groups. Serum sitosterol and campesterol were decreased significantly, while serum lathosterol was increased significantly or markedly in whole patients and also in each group. There were no significant changes in serum hsCRP in whole groups. Both serum MDA and CMP revealed significant or marked reductions in each group.
  
  
  CONCLUSIONS
  The present investigation suggests that the combination therapy of the ezetimibe and statin drugs is potential to remarkably reduce serum LDL-C, plant sterols, MDA and CMP, and therefore might lead to prevent atherosclerosis.
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Rika
authors: R
authors: Naruse
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Ken-ichiro
authors: K
authors: Hori
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Tomoko
authors: T
authors: Terasawa
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Kenji
authors: K
authors: Hara
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Mariko
authors: M
authors: Suetsugu
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Kohzo
authors: K
authors: Takebayashi
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan.
authors: Kimio
authors: K
authors: Morita
authors: Department of Endocrinology and Metabolism, Dokkyo Medical University School of Medicine, Mibu-machi, Tochigi 321-0293, Japan.
authors: Yoshimasa
authors: Y
authors: Aso
authors: Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya 343-8555, Japan. Electronic address: t-inukai@dokkyomed.ac.jp.
authors: Toshihiko
authors: T
authors: Inukai
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D002784:Cholesterol / Q000008:administration & dosage; D003324:Coronary Artery Disease / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D018384:Oxidative Stress; D010840:Phytosterols / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010840:Phytosterols; C001521:lathosterol; D002784:Cholesterol; D000069438:Ezetimibe
keywords: Ezetimibe; Lathosterol; Plant sterols; Statin drugs; Type 2 diabetes