Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance.
Acarbose, an alpha-glucosidase inhibitor, is administered to control blood glucose levels. The drug also reduces the risk of cardiovascular disease, but the underlying mechanism is still to be elucidated. We therefore hypothesized that treatment with acarbose ameliorates the atherogenecity of low-density lipoprotein (LDL), a key molecule in atherogenesis. Patients with impaired glucose tolerance were or were not treated with acarbose (acarbose-treated group [n = 20] and control group [n = 20], respectively) for 3 months under dietary therapy. The oxidative susceptibility of LDL was determined by measuring lag time for the formation of dienes in the presence of CuSO(4). The lag time was significantly longer in the acarbose-treated group than in the control group before treatment. Moreover, the density gradient lipoprotein separation and disk polyacrylamide gel electrophoresis analyses showed that acarbose reduced the amount of small dense LDL, a more atherogenic and oxidatively susceptible form of LDL. We also found that the fatty acid composition of LDL changed after the treatment: polyunsaturated (omega-3) fatty acid, a beneficial substance for preventing cardiovascular disease, was significantly increased, whereas saturated fatty acids and triglyceride were decreased in the LDL of the acarbose-treated group. The present findings suggest that acarbose treatment reduces the risk of cardiovascular diseases by ameliorating the atherogenecity of LDL.
Inoue
Ikuo
I
Department of Diabetic and Endocrinology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan. i1901018@saitma-med.ac.jp
Shinoda
Yuichi
Y
Nakano
Takanari
T
Sassa
Masatoshi
M
Goto
Sei-ichi
S
Awata
Takuya
T
Komoda
Tsugikazu
T
Katayama
Shigehiro
S
D020909:Acarbose / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000517:prevention & control*; D005227:Fatty Acids / Q000032:analysis; D018149:Glucose Intolerance / Q000188:drug therapy*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000633:toxicity*; D008079:Lipoproteins, VLDL / Q000097:blood; D047493:PPAR alpha / Q000502:physiology; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D047493:PPAR alpha; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D020909:Acarbose