Thiazolidinediones such as troglitazone and pioglitazone ameliorate dyslipidemia in type 2 diabetic patients by improving insulin resistance. The levels of serum triglycerides, nonesterified fatty acids, total cholesterol,and LDL cholesterol decrease after administration of these agents, while HDL cholesterol increases(1,2,3). These effects are helpful in preventing the development of atherosclerosis in diabetic patients. On the other hand, troglitazone has also been known to increase serum lipoprotein(a) [Lp(a)](4,5),a known atherogenic lipoprotein(6). To our knowledge, there is no report on the effect of pioglitazone on serum levels of Lp(a). Therefore,we investigated serum levels of Lp(a) and remnant-like particle cholesterol(RLP-C), a lipid known to act atherogenetically(7), before and after the administration of pioglitazone in type 2 diabetic patients.
Eight type 2 diabetic patients (five men and three women; mean age [mean± SEM] 60.8 ± 3.7 years) were included. Six enrolled patients had been receiving sulfonylureas, while the other two were on diet therapy only. Because of high levels of HbAlc, pioglitazone administration(15 or 30 mg/day) was added to previous treatment. The patients were instructed not to alter their eating patterns and exercise habits. Their preexisting medications (if any) remained unchanged during the treatment period. HbAlc and serum levels of triglyceride, total cholesterol,HDL cholesterol, Lp(a), and RLP-C were measured before and 3 months after pioglitazone administration. HbAlc levels were measured by a high-performance liquid chromatogrophy method with a normal laboratory range of 4.7-5.8%. Serum levels of triglyceride, total cholesterol, and HDL cholesterol were measured by standard laboratory techniques. Serum Lp(a)levels were measured by latex immunoassay with a rabbit monoclonal anti-human Lp(a) antibody, whereas serum RLP-C levels were measured by immunoadsorption assay using mouse monoclonal anti-human apolipoprotein (apo)B-100 and anti-human apoA-1 immunoaffinity mixed gel (normal range <40 and <7.5 mg/dl, respectively). This study was approved by the institutional review board, and all participants gave their informed consent.
The patient's HbAlc levels were improved from 7.9 ± 0.3 to 7.3 ± 0.3% by the addition of pioglitazone. Pioglitazone decreased serum triglyceride levels (from 191.3 ± 32.2 to 156.3 ± 35.5 mg/dl, P < 0.05) and increased serum HDL cholesterol levels (from 49.4 ± 3.9 to 58.6 ± 4.3 mg/dl, P < 0.05), whereas serum total cholesterol levels were unchanged (from 225.0 ± 18.0 to 225.0 ± 15.8 mg/dl). Serum Lp(a) levels were essentially unchanged(20.0 ± 6.8 to 19.9 ± 4.9 mg/dl). On the other hand, serum RLP-C levels were significantly decreased from 8.2 ± 1.9 to 7.2 ± 1.9 mg/dl (P < 0.05).
Previous studies demonstrated that thiazolidinediones have an inhibitory effect on the development of atherosclerosis through several mechanisms(8,9,10,11). This is the first report to clarify the relationship between pioglitazone and serum levels of Lp(a) and RLP-C. While pioglitazone did not influence serum Lp(a) levels, it decreased serum RLP-C levels. Concerning the effect on serum Lp(a), another thiazolidinedione, troglitazone has been known to increase serum Lp(a) levels(4,5). Because Lp(a) is known as an atherogenic lipoprotein(6), pioglitazone is superior to troglitazone in preventing atherosclerosis. Furthermore, pioglitazone may prevent the development of atherosclerosis due to the reduction of serum RLP-C levels. Our patient population was small in this study, so further studies will be needed to clarify the relationship between pioglitazone and serum levels of Lp(a) and RLP-C.
