title: Metformin reduces circulating malondialdehyde-modified low-density lipoprotein in type 2 diabetes mellitus.
abstract: OBJECTIVE
  Type 2 diabetes is known to be associated with increasing cardiovascular mortality. Malondialdehyde-modified LDL (MDA-LDL) is an oxidized LDL and is increased in patients with diabetes or hypertriglyceridemia. Elevated MDA-LDL has been reported to be a risk factor of atherosclerosis or cardiovascular disease. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and a new class of hypoglycemic agents. In this study, the effects of increasing the dose of metformin and add-on sitagliptin on MDA-LDL were examined in type 2 diabetes patients.
  
  
  METHODS
  Seventy patients with type 2 diabetes, inadequately controlled despite on-going treatment with metformin 500 mg/day, were enrolled in this randomized controlled trial. The patients received additional metformin (500 mg/day) or sitagliptin (50 mg/day) for 6 months, and changes in metabolic parameters including MDA-LDL were evaluated.
  
  
  RESULTS
  After 6 months of treatment, add-on sitagliptin (n=35) improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) to significantly greater extent than increasing the dose of metformin (n=35). There were no differences in total cholesterol and low-density lipoprotein cholesterol levels between two groups. MDA-LDL levels (mean ± S.E.) decreased significantly with increasing the dose of metformin (from 94.40 ± 6.35 to 77.83 ± 4.74 U/L, P < 0.005), but remained unchanged with add-on sitagliptin treatment (from 89.94 ± 5.59 to 98.46 ± 6.78 U/L, p > 0.05). Multiple linear regression analysis identified increasing the dose of metformin treatment as the only independent factor associated with decreased MDA-LDL (β coefficient 0.367, P < 0.0119), and no significant correlation between change in MDA-LDL and fasting blood glucose or HbA1c.
  
  
  CONCLUSIONS
  These results suggest that increasing the dose of metformin improves serum MDA-LDL levels in type 2 diabetes mellitus.
authors.affiliation: . 600137om@sakura.med.toho-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohira
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Saiki
authors.forename: Noriko
authors.initials: N
authors.lastname: Ban
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kawana
authors.forename: Daiji
authors.initials: D
authors.lastname: Nagayama
authors.forename: Ayako
authors.initials: A
authors.lastname: Nagumo
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Murano
authors.forename: Kohji
authors.initials: K
authors.lastname: Shirai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives* / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL; D011719:Pyrazines; D014230:Triazoles; C569869:malondialdehyde-low density lipoprotein, human; D008315:Malondialdehyde; D008687:Metformin; D000068900:Sitagliptin Phosphate