RAPID COMMUNICATION: Inhibitory Effect of Pioglitazone on Carotid Arterial Wall Thickness in Type 2 Diabetes

Abstract

There have been increasing evidences that thiazolidinediones, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, may have some antiatherogenic actions. We have previously reported that troglitazone has a potent inhibitory effect on common carotid arterial intima-media thickness (IMT) in subjects with type 2 diabetes. However, some studies suggested a possibility that PPARgamma activators may have protoatherogenic actions, raising concern about their detrimental effects in diabetic subjects. In the present study, we investigated the effect of treatment with pioglitazone, another PPARgamma agonist, on IMT in a total of 106 Japanese subjects with type 2 diabetes. Pioglitazone (30 mg daily) was administered for 6 months in 53 patients. Compared to control group (n = 53), the group given pioglitazone showed a significant decrease in IMT as early as 3 months after the administration. The decrease in IMT was also found after 6 months (IMT change: -0.084[SE 0.023] mm vs. control 0.022[SE 0.006] mm, P < 0.001), although the difference between those after 3 and 6 months did not reach any statistical significance. These findings indicate that thiazolidinediones cause an inhibition of early atherosclerotic process PPARgamma activation.

Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

“…It has been reported that IMT was reduced by 0.084 0.023 mm (mean SEM) when pioglitazone was administered to patients with type 2 diabetes for 6 months, and increased by 0.022 0.006 mm in a non-pioglitazone (control) group 17) . The upper confidence limit of changes in IMT in the pioglitazonetreated group was calculated to be 0.054 mm and the lower confidence limit of changes in IMT in the non-pioglitazone group was calculated to be 0.014 mm.…”

Effects of telmisartan and losartan on cardiovascular protection in Japanese hypertensive patients

“…31 Treatment with pioglitazone has previously been reported to decrease the progression of IMT in Japanese type 2 DM patients. 32 In TALENT, telmisartan treatment significantly inhibited the progression of IMT of common carotid artery compared with losartan. Cross-sectional studies have demonstrated that the age-related increases in common IMT were about 0.010 mm per year in healthy men and about 0.014 mm per year in healthy women.…”

Effect of pioglitazone on progression of subclinical atherosclerosis in non-diabetic premenopausal Hispanic women with prior gestational diabetes

“…To our knowledge, all of these studies were in older individuals with type 2 diabetes. Koshiyama et al [9] reported a significant reduction in CIMT in type 2 diabetic patients (mean age of 62 years) during 3-6 months of pioglitazone treatment compared to placebo treatment. Langefeld et al [10] reported a significant reduction in CIMT in type 2 diabetic patients (mean age of 63 years) treated with pioglitazone as compared to glimepiride for 24-week, the reduction of CIMT was independent of glycemic control.…”

“…Clinically, thiazolidinediones (TZDs) have had little [7] or no [8] beneficial effects on the risk of acute cardiovascular events in cohorts with average ages in the 50-60s or higher. On the other hand, at least three members of the class have been shown to reduce carotid intima-media thickness in individuals with established diabetes [9][10][11][12][13][14] and in nondiabetic individuals with known coronary disease [15]. Reasons for the apparent dissociation between promising mechanistic and CIMT effects of TZDs and their lack of impact on clinical cardiovascular events remain unexplained, but could be due to a dissociation between antiatherogenic effects of the drugs and their impact on mechanisms for acute arterial occlusion.…”