Effect of gliclazide on thromboxane B2, parameters of haemostasis, fluorescent IgG and lipid peroxides in non-insulin dependent diabetes mellitus.
Abnormalities of platelet aggregation, and increased levels of lipid peroxides and denatured proteins have been implicated in the pathogenesis of diabetic microangiopathy. Seventeen non-insulin dependent diabetics (mean age 65.7) on established sulphonylurea therapy were converted to an equivalent dose of gliclazide. They were studied at baseline and intervals to 36 weeks. Thromboxane B2 (TXB2) and beta thromboglobulin (beta TG) were measured by radioimmunoassay. Lipid peroxides were measured as total diene conjugates (DC) by scanning UV spectrophotometry and thiobarbituric acid reactivity (TBA) by absorbance at 532 nm. Oxidation products of proteins were represented by fluorescence/UV ratio of immunoglobulin G (*IgG) separated from serum by HPLC. Glycaemic control remained stable throughout the study. TXB2 fell from 734 +/- 233 ng/l at 0 weeks to 488 +/- 155 at 36 weeks, p less than 0.001 and beta TG from 120 +/- 70 ng/ml to 48 +/- 18 at 24 weeks, p less than 0.005. Lipid peroxides fell between 0 and 36 weeks; DC from 0.71 +/- 0.28 to 0.32 +/- 0.09, p less than 0.001 and TBA from 29.6 +/- 22.4 to 4.0 +/- 2.2, p less than 0.001. Fluorescent IgG ratio fell from 1.44 +/- 0.36 to 0.32 +/- 0.07, p less than 0.001. This data provides evidence for a specific action of gliclazide on thromboxane synthesis and platelet aggregation. This is independent of glycaemic control and may in part be mediated by the observed fall in lipid peroxides.
Florkowski
C M
CM
Department of Medicine, East Birmingham Hospital, UK.
Richardson
M R
MR
Le Guen
C
C
Jennings
P E
PE
O'Donnell
M J
MJ
Jones
A F
AF
Lunec
J
J
Barnett
A H
AH
D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D019270:Fructosamine; D005907:Gliclazide / Q000627:therapeutic use*; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008054:Lipid Peroxides / Q000097:blood*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood*
D001798:Blood Proteins; D019270:Fructosamine; D005907:Gliclazide; D005905:Glyburide; D006442:Glycated Hemoglobin; D006595:Hexosamines; D007074:Immunoglobulin G; D008054:Lipid Peroxides; D013453:Sulfonylurea Compounds; D013929:Thromboxane B2