Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension

Hypertension is common in patients with type 2 diabetes mellitus (DM), and contributes to the progression of its complications in patients with diabet es. Doxazosin is a selective alpha 1-adrenoceptor-blocking anti-hypertensiv e agent and has a favorable impact upon lipid metabolism. We investigated t he effect of doxazosin on the lipid metabolism in hypertensive patients wit h type 2 diabetes, especially low-density lipoprotein (LDL) particle size t hat is associated with many elements of the insulin resistance syndrome. Cr oss-sectional study (n = 19) was designed to determine whether doxazosin, a dministered with an angiotensin II converting enzyme inhibitor (ACEI) and a Ca antagonist, affects LDL particle size. As a follow-up study (n = 6), li pid and glucose metabolism and LDL particle size were followed for 12 weeks before and after the initiation of doxazosin administration (1-4 mg/day). The average size of LDL particle was significantly larger in the patients t reated with doxazosin (LDL-migration index (LDL-MI): 0.348 +/- 0.027) than those in the patient treated without doxazosin (0.378 +/- 0.035), although LDL cholesterol levels did not differ between the two groups. The plasma gl ucose and HbAlc levels remained unchanged. Lipid profile showed normolipemi a throughout the period of the study. However, LDL particle size was demons trated to become larger during the following period. Small LDL fraction (LD L3-7) diminished remarkably and large LDL (LDL1-2) increased on the polyacr ylamide gel electrophoresis (PAGE) LDL system (LipoPrint). From this pilot study, it was concluded that doxazosin is a useful anti-hypertensive agent for hypertensive type 2 diabetic patients in improving the size of LDL part icle. (C) 2000 Elsevier Science Inc. All rights reserved.