We read with interest an article by Aronoff et al. (1), which indicated that monotherapy of pioglitazone, a peroxisome proliferator–activated receptor (PPAR)-γ agonist, can improve lipid profile as well as glycemic control in type 2 diabetes. However, because they evaluated dyslipidemia in the fasted state, as most investigators do, it remains unknown whether pioglitazone may ameliorate postprandial dyslipidemia, which has recently been suggested to be an independent risk factor of atherosclerosis (4,5,6). We have previously indicated that troglitazone, another PPAR-γ agonist, can cause a decrease in postprandial triglyceride levels in subjects with type 2 diabetes, although there is no significant relationship between a decrease in postprandial triglyceride levels and a decrease in intima-media thickness (IMT) of the common carotid artery (2,3).

In the present study, we investigated whether pioglitazone, another PPAR-γ agonist, can decrease postprandial triglyceride in type 2 diabetes. Subjects included a total of 150 (87 men and 63 women, mean ± SEM age 61.1 ± 0.8 years) Japanese subjects with type 2 diabetes. HbA1c, total cholesterol, and postprandial triglycerides were measured 3 and 6 months after pioglitazone in the subjects receiving pioglitazone (30 mg/day) in combination with sulfonylurea drugs (n = 75) and in the control subjects, who were only receiving sulfonylurea drugs (n = 75). Postprandial triglyceride levels were examined 2 h after the conventional breakfast, as described previously (2). Although HbA1c showed a statistically significant decrease in comparison with control subjects (−0.885 ± 0.118 vs. 0.072 ± 0.130%, respectively, P < 0.05), there was no statistically significant change in total cholesterol (197.1 ± 4.7 vs. 202.7 ± 3.6 mg/dl, P = 0.350) or in postprandial triglycerides (150.3 ± 11.6 vs. 152.0 ± 12.4 mg/dl, P = 0.921).

Various PPAR target genes involved in fatty acid metabolism, such as lipoprotein lipase, have been identified to have PPAR response elements (7), which may, at least partly, result in an inhibitory effect of PPAR-γ agonists on plasma triglyceride levels. This preliminary result, however, suggests that pioglitazone does not decrease postprandial dyslipidemia unlike troglitazone, suggesting a possibility that PPAR-γ agonists may act differently on postprandial triglycerides. Taken together with our previous results, which showed that there is no relationship between a decrease in postprandial triglyceride and that in IMT after troglitazone (2,3), and with the fact that there is no correlation between postprandial triglyceride and IMT in a total of 250 subjects with type 2 diabetes (H. Koshiyama, unpublished data), it appears that postprandial triglyceride has no great impact on early atherosclerotic process, at least, in Japanese subjects with type 2 diabetes.

1
Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RL: Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes.
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2000
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Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H: Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes.
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Koshiyama H, Tanaka S, Minamikawa J, Nakao K: Relationship between postprandial triglyceride level and intima-media thickness of carotid artery after troglitazone treatment in type 2 diabetes. In Lipoprotein Metabolism and Atherogenesis. Kita M, Yokode M, Eds. Tokyo, Springer, 2000, p. 154–156
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Ryu JE, Howard G, Craven TE, Bond MG, Hagaman AP, Crouse JR: Postprandial triglyceridemia and carotid atherosclerosis in middle-aged subjects.
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Uiterwaal CS, Grobbee DE, Witteman JC, van Stiphout WA, Krauss XH, Havekes LM, de Bruijn AM, van Tol A, Hofman A: Postprandial triglyceride response in young adult men and familial risk for atherosclerosis.
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Grønholdt M-LM, Nordestgaard BG, Nielsen TG, Sillesen H: Echolucent carotid artery plaques are associated with elevated levels of fasting and postprandial triglyceride-rich lipoproteins.
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Address correspondence to Hiroyuki Koshiyama, Division of Endocrinology and Metabolism, Department of Internal Medicine, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Hyogo 660-0828, Japan. E-mail: [email protected].

2001