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15 July 1998 | Volume 129 Issue 2 | Pages 162-163
Several recent studies suggest the association of a preponderance of small, dense low-density lipoprotein (LDL) particles, potent atherogenic lipoproteins, with insulin resistance [1, 2]. However, it is still unknown whether insulin resistance or other factors related to insulin resistance directly regulate LDL size. We evaluated the direct association between insulin resistance and LDL size by treating patients with troglitazone, a new oral hypoglycemic agent [3] that ameliorates insulin resistance in patients with type 2 diabetes mellitus [4].
Thirty patients who had type 2 diabetes treated with sulfonylurea were enrolled in this study. The levels of fasting plasma glucose, hemoglobin A1c, and insulin were significantly suppressed by treatment with troglitazone (400 mg/d) for 3 months (Table 1). The average LDL-particle diameter, measured by 2% to 16% gradient polyacrylamide gel electrophoresis [5], was remarkably enlarged (Table 1). Thus, the number of patients with LDL pattern B (diameter LETTER
Troglitazone and Small Low-Density Lipoprotein in Type 2 Diabetes
TO THE EDITOR: 
25.5 nm) was dramatically reduced from 13 to 1. Although plasma triglyceride levels were not changed significantly, an excellent correlation between increase in LDL size and decrease in plasma triglyceride levels was seen (r = –0.508;P < 0.001) during treatment. No correlations were found between changes in LDL size and plasma glucose, hemoglobin A1c, or insulin levels. Because the hypoglycemic action of troglitazone is completely attributed to decrease in insulin resistance [3, 4], our preliminary study suggests that LDL size is more directly influenced by triglyceride. metabolism than by improvement of insulin sensitivity itself. Troglitazone may have favorable effects on the prevention of coronary heart disease in patients with type 2 diabetes, in part through the reduction of small LDL particles.
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1. Reaven GM, Chen Y-DI, Jeppesen J, Mahcux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J Clin Invest. 1993; 92:141-6.
2. Selby JV, Austin MA, Newman B, Zhang D, Quesenberry CP, Mayer EJ, et al. LDL subclass phenotypes and the insulin resistance syndrome in women. Circulation. 1993; 88:381-7.[Abstract]
3. Fijiwara T, Yoshioka S, Yoshioka T, Ushiyama I, Horikoshi H. Characterization of new oral antidiabetic agent CS-045: studies in KK and ob/ob mice and Zucker fatty rats. Diabetes. 1988; 37:1549-58.
4. Iwamoto Y, Kuzuya T, Matsuda A, Awata T, Kumakura S, Inooka G, et al. Effect of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM. Diabetes Care. 1991; 14:1083-6.
5. Krauss RM, Burke DJ. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982; 23:97-104.
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